Sequential Norrish type II photoelimination and intramolecular aldol cyclization of α-diketones: Synthesis of polyhydroxylated cyclopentitols by ring contraction of hexopyranose carbohydrate derivatives

FULL PAPER

Carbohydrates

D. Alvarez-Dorta, E. I. Leꢀn,*

A. R. Kennedy, A. Martꢁn,

I. Pꢂrez-Martꢁn, C. Riesco-Fagundo,

E. Suꢃrez* ..................... &&&& — &&&&

Just light and heat! Visible-light pho-

toexcitation of the innermost carbonyl

of 2,3-diulose triggers an unprece-

dented Norrish type II photoelimina-

tion and uncatalyzed aldol sequential

rearrangement through the thermal 5-

(enolexo)-exo-trig cyclization of the

acyclic photoenol intermediate. The

process involves a pyranosyl ring con-

traction and the formation of a new

type of cyclopentitol derivatives with

high diastereoselectivity (see scheme;

R=acyl, alkyl, silyl group).

Sequential Norrish Type II Photoelimi-

nation and Intramolecular Aldol Cycli-

zation of a-Diketones: Synthesis of

Polyhydroxylated Cyclopentitols by

Ring Contraction of Hexopyranose

Carbohydrate Derivatives

Chem. Eur. J. 2013, 00, 0 – 0

ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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DOI: 10.1002/chem.201301230

Sequential Norrish Type II Photoelimination and Intramolecular Aldol

Cyclization of a-Diketones: Synthesis of Polyhydroxylated Cyclopentitols by

Ring Contraction of Hexopyranose Carbohydrate Derivatives

Dimitri Alvarez-Dorta,^[a]Elisa I. Leꢀn,*^[a]Alan R. Kennedy,^[b]Angeles Martꢁn,^[a]

Inꢂs Pꢂrez-Martꢁn,^[a]Concepciꢀn Riesco-Fagundo,^[a]and Ernesto Suꢃrez*^[a]

Abstract: The excitation of the inner-

most carbonyl of nono-2,3-diulose de-

rivatives by irradiation with visible-

high diastereoselectivity. In this last

step, the large deuterium kinetic iso-

tope effect found for the 1,5-hydrogen

atom transfer seems to indicate that

the aldol reaction runs through a con-

certed pericyclic mechanism. Owing to

the ready availability of pyranose

sugars of various configurations, this

protocol has been used to study the in-

fluence of pyranose ring-substituents

on the diastereoselectivity of the aldol

cyclization reaction. In contrast with

other pyranose ring contraction meth-

odologies no transition-metal reagents

are needed and the sequential rear-

rangement occurs simply by using visi-

ble light and moderate heating (0 to

608C).

light initiates

a sequential Norrish

type II photoelimination and aldol cyc-

lization process that finally gives poly-

functionalized cyclopentitols. The rear-

rangement has been confirmed by the

isolation of stable acyclic photoenol in-

termediates that can be independently

cyclized by a thermal 5-(enolexo)-exo-

trig uncatalyzed aldol reaction with

Keywords: carbohydrates

· cyclo-

pentitols · diketones · photochemis-

try · ring contraction

Introduction

served. The development of synthetic applications of this

1,5-hydrogen atom transfer reaction originated by a-dike-

tones has been scant.^[3]This is somewhat surprising since a-

diketones can be selectively activated over other photo-

chemically excitable groups, just by irradiation with visible

light (violet-blue interval, ca. 450 nm). We believe this may

be due to the lack of direct and general methods for their

synthesis, especially on sensitive substrates, and to the insta-

bility observed for some aliphatic a-diketones.

The photochemical behavior of monoketones has attracted

a great deal of attention from synthetic and theoretical per-

spectives, whereas comparatively much less evidence is

available on a-diketones.^[1]Both types of photoexcited car-

bonyls exhibit a remarkable regioselectivity of intramolecu-

lar 1,5-hydrogen transfer, to give a 1,4-biradical intermedi-

ate, which finally evolves following two competitive paths:

Norrish type II photoelimination and Norrish–Yang photo-

cyclization.^[2]Whereas photoelimination is usually the priori-

ty process with monoketones, a-diketones yield almost ex-

clusively 2-hydroxycyclobutanones by photocyclization.

Moreover, in a-diketones the 1,5-hydrogen abstraction ap-

parently occurs only from the external carbonyl, such that

the formation of acyl cyclobutanols has never been ob-

The conversion of carbohydrate derivatives into enantio-

pure polyfunctionalized cyclopentanes has been extensively

documented.^[4]Two general methodologies are currently

used: Ring closing of polyfunctionalized acyclic molecules

that most often involves multistep reaction sequences and

ring contraction of pyranoside carbohydrate derivatives,

which normally require a single synthetic step. These ring-

contraction methods represent a highly efficient biomimetic

approach to the synthesis of cyclopentanols.^[5]Several proce-

dures have been published, all of which start from conven-

iently modified carbohydrate derivatives and in general in-

volve a reductive ring-opening followed by an intramolecu-

lar reductive coupling using samarium or zirconium re-

agents. Representative examples with indication of starting

materials and reagents are: Hept-6-enopyranosides

[a] Dr. D. Alvarez-Dorta, Dr. E. I. Leꢁn, Dr. A. Martꢂn,

Dr. I. Pꢃrez-Martꢂn, Dr. C. Riesco-Fagundo, Prof. Dr. E. Suꢄrez

Instituto de Productos Naturales, y Agrobiologꢂa del C.S. I.C.

Carretera de la Esperanza 3, 38203 La Laguna, Tenerife (Spain)

Fax : (+34)922-260-135

E-mail: eila@ipna.csic.es

([Cp₂ZrCl₂]/BF₃·OEt₂)^[6]or (SmI₂/[Pd

(PPh₃)₄]),^[7]oct-6-eno-

ACHTUNGTRENNUNG

esuarez@ipna.csic.es

pyranosiduronate (SmI₂),^[8]hept-6-ynopyranosides (SmI₂/

[b] Dr. A. R. Kennedy

WestCHEM Department of Pure and Applied Chemistry

University of Strathclyde

295 Cathedral Street, Glasgow G1 1XL (UK)

[PdACHTNUTGRNEUNG

(PPh₃)₄]),^[7]6-deoxy-6-iodo-hexopyranoside (SmI₂),^[9]and

glucodialdo-1,5-hexopyranoside (SmI₂).^[10]

In connection with our ongoing research programs on the

Supporting information for this article is available on the WWW

under http://dx.doi.org/10.1002/chem.201301230.

reactivity of a-diketones^[11]and intramolecular hydrogen

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Synthesis of Polyhydroxylated Cyclopentitols

FULL PAPER

such as trehazoline, calditol, and bacteriohopanoids should

be particularly accessible through this methodology. We be-

lieve that this protocol is also uniquely suited to study the

effect of pyranose ring-substituents on the diastereoselectivi-

ty of the aldol cyclization reaction.

Results and Discussion

The present contribution is a study of the scope and the se-

lectivity of this reaction, as well as an effort to establish the

best conditions for this photoreaction and to demonstrate

the mechanism involved. This has been achieved by prepar-

ing a variety of 2,3-diuloses belonging to carbohydrates in

pyranose and furanose form.

Scheme 1. Photochemistry of nono-2,3-diulose 1. INHAT=intramolecu-

lar hydrogen atom transfer.

atom transfer (INHAT) promoted by alkoxyl radicals in car-

bohydrate chemistry,^[12]we present herein our results on the

photochemical reactivity of nono-2,3-diuloses (Scheme 1).^[13]

It is generally accepted that hydrogen atom abstraction by a

photoexcited carbonyl closely resembles the hydrogen atom

abstraction by alkoxyl radicals.^[1a,b]Therefore, one would

expect that in nono-2,3-diulose 1, in as much as the hydro-

gen atom at C5 is geometrically inaccessible, the abstraction

of H8 may proceed either by the external carbonyl (1,6-

HAT) or by the innermost carbonyl (1,5-HAT). Through re-

search conducted in our laboratory we have shown that

both types of processes can be carried out with alkoxyl radi-

cals. C-Glycosides possessing 1-hydroxymethyl^[14]and 1-hy-

Synthesis of a-C-propynyl glycosides: We based the prepara-

tion of these compounds on the a-ethynylation of sugars by

ꢀ

C-glycosidation using nBu₃SnC CSiMe₃in the presence of

trimethylsilyl triflate (TMSOTf) followed by desilylation of

the initial adducts, a methodology well established by the

groups of Isobe^[16]and Dondoni.^[17]Thus, gluco derivative 6

was obtained from acetate 3 through the silyl intermediate 5

in good yield (Scheme 2). Unfortunately, repeated attempts

droxyethyl^[15]tethers cyclized, with the PhI

to give 6,8-dioxabicyclo[3.2.1]octane (1,5-HAT) and 2,9-

dioxabicyclo[3.3.1]nonane (1,6-HAT) derivatives, respective-

ly.

ACHTUNGTRENN(NUG OAc)₂/I₂system,

AHCTUNGTRENNUNG

ACHTUNGTRENNUNG

As described in Scheme 1 the reaction of 2,3-diulose 1

proceeded by a sequential Norrish type II photoelimination

through the 3,8-biradical I; the intermediate photoenol II

subsequently formed was converted into a cyclopentane de-

rivative by a thermal OH-b-syn aldol cyclization. Finally, the

regenerated a-diketone reacts with the hydroxyl group at

C8 to give the hemiketal 2. Some features of these processes

deserve brief comment. Only visible light and moderate

heating are necessary for the reaction to take place, in con-

trast with the other ring contraction methods listed above

that require the presence of transition-metal reagents. As

mentioned before, Norrish type II photoelimination of a-di-

ketones is an extremely rare reaction, whereas the uncata-

lyzed aldol cyclization, in which a photoenol acts as a pre-

formed enolate, is unprecedented to our knowledge. As

noted, the stereocenters at C4 and C8 destroyed in the pho-

tochemical reaction are regenerated diastereoselectively

with inversion of configuration in the aldol cyclization step.

Owing to the ready availability of pyranose sugars of vari-

ous configurations, this protocol would provide access to

highly oxygenated 1,2-trans dialkylated cyclopentanes and

cyclopentanoid natural products, for example, prostaglan-

dins, brefeldin, and Corey lactone analogues. The synthesis

of systems with 1-(hydroxymethyl)cyclopentitol moieties

Scheme 2. Synthesis of nono-2,3-diuloses by oxidation of non-2-ynitols.

ꢀ

a) For the synthesis of 5 from 3: nBu₃SnC CTMS (2 equiv), TMSOTf

(2.5 equiv), CH₂Cl₂, MS 4 ꢅ, room temperature, 3 h, 66%; for the synthe-

ꢀ

sis of 7 from 3 (Method A): TMSC CMe (2 equiv), TMSOTf (3 equiv),

MeCN, MS 4 ꢅ, 08C, 2 h, 33%; for the synthesis of 7 from 3 (Method B):

ꢀ

n-Bu₃SnC CMe (2 equiv), TMSOTf (2 equiv), CH₂Cl₂, MS 4 ꢅ, room

ꢀ

temperature, 2 h, 82%; for the synthesis of 7 from 4: n-Bu₃SnC CMe

(2.5 equiv), BF₃·OEt₂(2 equiv), CH₂Cl₂, MS 4 ꢅ, room temperature, 1 h,

51%; b) NaOH (1.9 equiv), CH₂Cl₂/MeOH, room temperature, 2 h, 92%;

c) see text; d) [PdACHTNUTRGNEUNG(PPh₃)₄], (0.05 equiv), CuI (0.1 equiv), PhI (1 equiv), pi-

peridine, 808C, 1 h, 88%; e) O₃(excess), CH₂Cl₂, ꢁ788C, 2 h, then Me₂S

(2.1 equiv), 6 h, dark; f) Daylight-lamp irradiation, C₆D₆, 308C, N₂, 9 h,

then air, 48%, two steps. TMS=trimethylsilyl, OAc=acyl.

to accomplish the alkyne methylation by using several bases

(nBuLi, LDA, and NaH) and alkylating agents (MeI and

MeOTf) under a range of conditions gave none of the de-

sired product 7 and only starting material 6 was recovered

in all cases.^[18]A related attempt at C-glycosidation by treat-

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E. I. Leon, E. Suꢄrez et al.

ꢀ

ment of acetate 3 and commercially available TMSC CMe

pared from the corresponding non-2-ynitols by oxidation of

the triple bond with ozone (Method A)^[21]or NaIO₄/

RuO₂·xH₂O (Method B).^[22]a-Diketones using benzyl ether

as protective groups were better prepared by oxidation of

the triple bond with NaIO₄/RuO₂·xH₂O than by using the

ozone methodology. The a-diketones obtained as yellow oils

are in most cases stable for at least several months when

stored at ꢁ258C under nitrogen in the dark and can be puri-

fied by rapid silica gel column chromatography, although a

significant loss of material was generally observed. In all the

a-diketones the conformation of the pyranose ring was care-

fully studied by analysis of its vicinal coupling constant

values. A chair C₄conformation (equivalent to C₁in the

aldose series), in which the H8 and the diketone tether are

in a 1,3-diaxial relationship, appears to be essential for the

intramolecular hydrogen atom transfer (INHAT) reaction to

take place.

In our preliminary experiment, a [D₆]benzene solution of

a-diketone 1 was irradiated with a daylight lamp (Philips

master PL electronic, 23 W/865) at 308C until the yellow

color faded (3 h). Direct sunlight can also be used but the

reaction is usually slower and times are not reproducible. A

single diastereomer with a hexahydro-2H-cyclopenta[b]furan

bicyclic structure 2 was formed in 52% yield, and no other

isomers were detected by ¹H NMR spectroscopy of the

crude reaction mixture (Table 1). With the aim of establish-

ing the excitation behavior of the dicarbonyl system, a solu-

tion of 1 in [D₆]benzene con-

was similarly unproductive. After extensive experimentation

(see the Supporting Information) the a-C-propynyl gluco-

side 7 was obtained with good diastereoselectivity but in an

unacceptable maximum yield of 33%. Therefore, an alterna-

ꢀ

tive route was sought using nBu₃SnC CMe as glycosyl ac-

ceptor, which was prepared according to the procedure de-

veloped by Logue and Teng.^[19]The reaction catalyzed by

TMSOTf proceeded very smoothly to give 7 in good yield

and diastereoselectivity (90%, diastereomeric ratio (d.r.) a/

b, 10:1). Alternatively, by using glucopyranosyl fluoride 4 as

glycosyl donor and BF₃·OEt₂as catalyst the diastereoselec-

tivity was improved since almost only the a-isomer of the

product was detected. All the a-C-propynyl glycosides

shown in Tables 1–4 were prepared by using one of these

two methodologies or in some cases by simple functional

group modification between them. In general, the fluoride

method was preferred in substrates with acid-sensitive pro-

tectors (e.g., 15, Table 1), whereas the formation of highly

unstable fluorides, as in the furanoses 67–69 (Table 4), pre-

vents its utilization.

7

4

For comparative purposes in the photochemical experi-

ments, permethylated 2,6-anhydro-7,8-dideoxy-8-phenyl-d-

glycero-l-gulo-oct-7-ynitol (9) was prepared by Sonogashira

cross-coupling of alkyne 6 with iodobenzene.^[20]

9 (Scheme 2), 18–24 (Table 1), 38–43

(Table 2), 58–61 (Table 3), and 70–72 (Table 4) were pre-

Diketones 1,

taining the triplet quencher

pyrene (13 equiv) was irradiat-

Table 1. Synthesis and photolysis of 2,3-diuloses with a-d-glucopyranose stereochemistry.

ed at 308C for 12 h. The photo-

reaction was completely inhibit-

ed, confirming that the hydro-

gen abstraction occurs mainly

from the triplet state since

cleavage products promoted by

the singlet biradical were not

detected. Compound 2 is a crys-

talline solid whose structure

and stereochemistry was deter-

mined by extensive 1D and

2D NMR studies and confirmed

a-C-Propynyl glucoside

Method^[b]

2,3-Diulose

[%]^[a]

Product

ACHTUNGTRENNUNG

[%, d.r.]^[a,c]

[%]^[a]

7: R=R¹=OMe (90)

11: R=R¹=OBn (86)

12: R=OBn, R¹=ODPS

13: R=OBn, R¹=OAc

14: R=OBn, R¹=N₃

A

B

1: R=R¹=OMe^[d]

2: R=R¹=OMe (52)^[e]

18: R=R¹=OBn (62)

25: R=R¹=OBn (58)

19: R=OBn, R¹=ODPS (64)

20: R=OBn, R¹=OAc (47)

21: R=OBn, R¹=N₃(59)

26: R=OBn, R¹=ODPS (65, 5:1)

27: R=OBn, R¹=OAc (67, 1:0.9)

28: R=OBn, R¹=N₃(55, 1.3:1)

by X-ray crystallographic analy-

3

sis.^[23]In particular, the J_H4,H5

=

4.7 Hz (calcd 4.1 Hz), HMBC

correlations of H4 to C8 and

C9, and NOE interactions be-

tween the hydroxyl proton and

H4 and H9 as well as interac-

tions between 1-Me and H5

and H7 accounted for the b-syn

cyclization and the S stereo-

chemistry of the hemiketal.

Due to the flexibility of the cy-

clopentane, weighted average

³J_H,Hfor the ring protons were

calculated for the more popu-

15 (77)

A

22 (67)

29 (53, 10:3)

16: R=R¹=TBS (68)

17: R=Ac, R¹=TBS

A

23: R=R¹=TBS (75)

30: R=R¹=TBS (63)

24: R=Ac, R¹=TBS (73)

31: R=Ac, R¹=TBS (62, 10:3)

[a] Yield of the product isolated by using chromatography. [b] Method A: O₃(excess), CH₂Cl₂, ꢁ788C, 2 h,

then Me₂S (2.1 equiv), room temperature, dark. Method B: NaIO₄(4 equiv), RuO₂·xH₂O (8.8 mg), CCl₄/

CH₃CN/H₂O (1:1:1.5), room temperature, dark. [c] Hemiketal diastereomeric ratio, major isomer shown.

[d] Crude product of high purity but could not be purified on chromatography over silica. [e] Yield over three

steps. DPS=tert-butyldiphenylsilyl, TBS=tert-butyldimethylsilyl.

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Synthesis of Polyhydroxylated Cyclopentitols

FULL PAPER

lated conformers as determined by pseudorotational analy-

sis.^[24]Two conformers were obtained with pseudorotational

phase angle (P; north- and south-type, P_NP_S, respectively)

and populations, as indicated: E₆(P_N=346.48, 60%) and

⁶T₇/E₇(P_S=189.18, 40%; see Table 2S and Figure 1S in the

Supporting Information for details). The more stable con-

former is in close agreement with the ring conformation in

the solid state: ⁷T₆(P_N=358.58). A small but significant

⁴J_H5,H7coupling (ca. 1 Hz) can be detected, which is more

more related with the instability of the diulose itself.

The coupling constant J_H4,H5proved to be diagnostic in

3

distinguishing between the OH-b-syn and OH-a-syn aldol

3

cyclization (see below, J_H4a,H5b=2–4 Hz is much smaller

3

than J_H4b,H5b=9–10 Hz). However, due to the flexibility of

the cyclopentane ring the stereochemistries have been con-

firmed further by nuclear Overhauser effect spectroscopy

(NOESY) studies on minimized structures. In those com-

pounds 2 and 29–31 in which the experimental ring coupling

constants could be unequivocally determined, a conforma-

tional study by pseudorotational analysis has been per-

formed. Two relatively narrow pseudorotational ranges are

preferred for these d-glucose-derived cyclopentanes. In the

North-type conformations P ranges from 311 to 3468 (⁵E/⁵T₆

to E₆) were observed, whereas P values of 106–1898 (⁴T₅to

⁶T₇) were found for the conformations positioned in the

South region of the pseudorotational wheel (See Table 2S

and Figure 1S of the Supporting Information for details).

The next series of reactions explored the photolysis of

deoxy-2,3-diuloses 38–43 as described in Table 2. The reac-

tions proceeded analogously to the previously mentioned

examples in terms of yield and diastereoselectivity except

for 5-deoxy-diulose 38, which gave a 1:1 diastereomeric mix-

ture of OH-b-syn 44 and OH-a-syn 45 aldol cyclization

products after heating for 5 h at 608C. The photolysis mix-

ture was subjected to acetylation thus allowing for a partial

chromatographic separation of acetates 44 and 45.

6

consistent with the T₇/E₇conformation where both hydro-

gens are pseudoequatorial in a W-type planar arrangement.

The X-ray crystallographic structure indicated that the con-

figuration of the hemiketal is stabilized by an intramolecular

seven-membered hydrogen bond between the hydroxyl

group and the oxygen atom at C9. The reaction was moni-

tored by ¹H NMR spectroscopy but we were unable to

detect any photoenol II under these reaction conditions

(308C); nevertheless, at 08C a doublet at d=5.56 ppm (J=

9 Hz) and a broad singlet exchangeable with D₂O at d=

6.73 ppm assignable to the transient photoenol could be ob-

served.^[25]Upon warming to room temperature these signals

rapidly disappeared completely, the cyclized product 1 being

the only one observable after a few minutes.

Unfortunately, the photolysis of phenyl diulose 9 failed

completely to undergo the desired 1,5-HAT, instead provid-

ing the photoenol III as the only intermediate detectable by

¹H NMR spectroscopy (Scheme 2).^[25,26]This intermediate

could not be isolated and was rapidly oxidized during the

work-up, presumably by the ambient oxygen, ultimately

leading to the degraded lactone 10 in moderate yield. A

possible inversion of the pyranose ring in the diketone was

discarded by the coupling con-

The OH-b-syn cyclization structure was assigned to 44 by

3

the J_H4a,H5b=4.4 Hz and substantiated by the observation of

NOESY correlations between 1-Me and H7, and H4 and

3

H6. Moreover, a larger J_H4b,H5b=9.8 Hz coupling constant

stants, which are undoubtedly

7

consistent with a C₄conforma-

tion.

The other 2,3-diuloses be-

Table 2. Synthesis and photolysis of mono- and di-deoxy-2,3-diuloses in pyranose form.

a-C-Propynyl glycoside

[%, d.r.]^[a]

Method^[b]

2,3-Diulose

[%]^[a]

Product

ACHTUNGTRENNUNG

[%, d.r.]^[a,c]

G

longing to d-glucopyranose

series 18–24 (Table 1) with dif-

ferent substituents at C7 and

C9, vicinal carbon atoms in the

INHAT, were synthesized to

determine the influence of

steric and electronic effects in

both the reactivity of the diradi-

cal intermediate I and the dia-

stereoselectivity of the aldol re-

action. The reactions involved

in this transformation do not

seem to be influenced greatly

by the steric bulkiness or elec-

tronegativity of the protecting

groups, similar yields being ob-

tained and only products from

OH-b-syn aldol cyclization

being observed. The somewhat

lower yields obtained in the

32 (86)

B

38 (63)

44 (20)

45 (20)

33: R=Me (69, 22:1)

34: R=DPS (87, 14:1)

A

39: R=Me (65)

40: R=DPS (77)

46: R=Me (57)

47: R=DPS (75)

35: R=Me (91)

36: R=DPS

37: R=(NO₂)₂Bz

A

B

41: R=Me (69)

48: R=Me (52)

49: R=DPS (61, 10:1)

42: R=DPS (71)

43: R=(NO₂)₂Bz (71)^[d]

[a] Yield of the product isolated by using chromatography. [b] Method A: O₃(excess), CH₂Cl₂, ꢁ788C, 2 h,

then Me₂S (2.1 equiv), dark. Method B: NaIO₄(4 equiv), RuO₂·xH₂O (8.8 mg), CCl₄/CH₃CN/H₂O (1:1:1.5),

room temperature, dark. [c] Hemiketal diastereomeric ratio, major isomer shown. [d] Thermolysis of 43 was

synthesis of 2 and 29 could be never realized. Bz = benzyl.

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E. I. Leon, E. Suꢄrez et al.

and NOESY correlations between 1-Me and H6, and H4

and H7 were consistent with an OH-a-syn cyclization struc-

ture for the isomer 45.

The most unexpected results were found for the deoxy

compounds 40–43, which were transformed into the inter-

mediate photoenols 50–53 upon irradiation at 15–358C

(Scheme 3). Compounds 50–53, which are surprisingly stable

tion of the primary alcohol (e.g., 3,5-dinitrobenzoate 53)

were unsuccessful.

We next prepared 2,3-diuloses of the d-manno 58 and d-

galacto 59–61 series to evaluate the influence of the C5 and

C7 stereochemistry in the diastereoselectivity of the aldol

reaction (Table 3). We anticipated on the basis of the previ-

ous experiment with 5-deoxy-diulose 38 (Table 2) that the

aldol cyclization could show a marked dependence on the

stereochemistry of the substituents at C5. This was indeed

the case; the photolysis of 58 at 308C and subsequent heat-

ing at 508C led exclusively to the formation of the a-syn

isomer 62, albeit in moderate yield. The crude reaction had

to be acetylated to facilitate the purification of 62 from a

complex reaction mixture. In the mannose skeleton, an al-

ternative 1,5-HAT reaction of the H5a proton by the exter-

nal carbonyl under classical Norrish-Yang conditions is pos-

sible. Thus, competitive abstraction of H8a and H5a may

account for the somewhat lower efficiency of this process

but we have been unable to isolate or identify any side

products to confirm this hypothesis.

Scheme 3. Synthesis and aldol reactions of stable photoenols 50–53.

a) Daylight-lamp irradiation, C₆D₆; b) heat at 408C for the synthesis of

47 (78%) from 50, and at 608C for the synthesis of 48 (52%) and 49

(61%) from 51 and 52, respectively. Thermolysis of 53 was never realiz-

ed.

1

The H NMR spectrum of the permethylated d-galactose

model 59 exhibits ring coupling constants that strongly point

4

to a C₇chair conformation. It was therefore not very sur-

prising that the photochemical reaction gave 2,3,4,6-tetra-O-

methyl-a-d-galactono-1,5-lactone as the only detectable

product in 80% yield. Since in this geometric arrangement

the a-diketone tether and the H8a are in a 1,3-diequatorial

disposition, the 1,5-HAT by the internal carbonyl is impossi-

ble. The excited carbonyl preferentially abstracts the axial

H4b to give a 3,4-photoenol intermediate (such as III,

Scheme 2) which is subsequently and presumably degraded

to the lactone by adventitious oxygen during the workup.

The tert-butyldiphenylsilyl (DPS) derivative 60 was then

synthesized in the hope that an extremely bulky protecting

group at the 9-primary alcohol causes a flip of the C-glyco-

at room temperature for extended periods, could be isolated

without significant contamination by either the starting ma-

terial or the respective cyclized product. The oily crude resi-

dues did not withstand chromatographic purification over

silica gel or alumina but were pure enough to allow com-

plete analytical and spectroscopic characterization. A nucle-

ar Overhauser effect (NOE) interaction between the methyl

ketone and the vinyl proton is indicative of the Z configura-

tion for the double bond as shown in Scheme 3. Photoenol

50 obtained by photolysis of 40 at 258C cyclized upon heat-

ing at 408C in light-protected benzene solution for 8 h to

afford carbocycle 47. Photoenols 51 and 52, which are ther-

mally more stable, were cy-

7

side conformation to the C₄chair.^[27]Fortunately, the ring

3

coupling constants (³J_H4,H5=6.9, ³J_H5,H6=8.5, and J_H6,H7

=

clized in the dark at 608C to

give carbocycles 48 and 49, re-

spectively.

Table 3. Synthesis and photolysis of 2,3-diuloses with a-d-manno- and a-d-galacto-pyranose stereochemistry.

a-C-Propynyl

Method^[b]

2,3-Diulose

[%]^[a]

Product

[%]^[a]

glycoside [%, d.r.]^[a]

These thermal experiments,

performed with strict exclusion

of light, confirm that the aldol

reaction proceeded with a high

degree of diastereoselectivity,

resulting in the exclusive forma-

tion of syn-aldols. We did not

find any anti-aldol product that

(having the a-diketone moiety

unprotected) could have been

destroyed by secondary photol-

ysis in the prior illuminated ex-

periments. Several attempts to

obtain suitable crystals of the

photoenol for X-ray crystallo-

54

B

58 (53)

62 (30)

55: R=Me (85, 1:1.1)

56: R=DPS

57: R=Ac (87)

A

B

59: R=Me (58)^[c]

60: R=DPS (64)

61: R=Ac (48)

63: R=DPS (23)

65: R=Ac (19)

64: R=DPS (46)

66: R=Ac (57)

[a] Yield of the product isolated by using chromatography. [b] Method A: O₃(excess), CH₂Cl₂, ꢁ788C, 2 h,

then Me₂S (2.1 equiv), dark. Method B: NaIO₄(4 equiv), RuO₂·xH₂O (8.8 mg), CCl₄/CH₃CN/H₂O (1:1:1.5),

graphic analysis by derivatiza- room temperature, dark. [c] Irradiation of 59 led to 2,3,4,6-tetra-O-methyl-d-galactono-1,5-lactone exclusively.

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Synthesis of Polyhydroxylated Cyclopentitols

FULL PAPER

2.6 Hz) confirmed this assumption and the photolysis–heat-

ing process on 60 afforded a mixture of two diastereomeric

cyclopentitols, which was acetylated and separated into 63

and 64 after careful chromatography (d.r. 1:2). The inter-

mediate photoenol could be fully characterized by monitor-

ing the reaction by using H NMR spectroscopy and subse-

quent heating at 708C was necessary to accomplish the aldol

cyclization.

(⁷T_o), wherein the a-diketone tether and the hydrogen at C7

lie in a syn-1,3-pseudo-diequatorial relationship. The dis-

tance between the oxygen at C3 and the extractable hydro-

gen at H7 on the minimum energy conformer was calculated

as indicative of the 1,5-HAT feasibility. Since it is generally

accepted that a narrow range of distances of approx. 2.5–

3.0 ꢅ are required for the reaction to take place, the ob-

1

tained value of d_{C3 O···H7}=4.7 ꢅ precludes any photochemi-

=

The structure of 63 and 64 as b-syn and a-syn cyclization

isomers, respectively, was assigned on the previously com-

cal hydrogen abstraction.^[28]

The abstraction at H7 is not geometrically feasible in the

d-ribo isomer 71b, but the abstraction of H5 by the excited

external carbonyl to result in a Yang photocyclization is

worthy of consideration. Notwithstanding, the photolysis of

71b gave the same lactone 73 in similar yield, demonstrating

that in these sugar derivatives photoenolization also com-

petes favorably with the Yang cyclization.^[26]In contrast to

d-ribo derivative 70a, the furanose ring of the isomeric d-

3

mented basis: The J_H4,H5coupling constant, which is smaller

for the b-syn isomer (³J_H4a,H5b=2.9 Hz for 63 versus

³J_H4b,H5b=9.5 Hz for 64), and NOESY experiments. To calcu-

late the ring coupling constants and NOE interaction the

most populated conformer was determined to be ⁷T₆for

both isomers (P=6.9 for 63 and 355.88 for 64) by using

pseudorotational analysis (see the Supporting Information

for details). Similar results were observed in the reaction of

9-acetyl derivative 61: a 1:3 mixture of 65 and 66 was ob-

tained in good overall yield (76%), in which the a-syn

isomer was also the major product.

o

lyxo 72 adopts a conformation E (P=868) with the a-dike-

tone and the H7 in a syn-1,3-pseudo-diaxial relationship. In

the global minimum the INHAT distance now possesses an

ideal value of 2.53 ꢅ and the photoelimination proceeded

smoothly to give 75 presumably by intramolecular hemike-

talization of the intermediate photoenol 74b. a,b-Unsaturat-

ed ketone 75 could not withstand chromatographic purifica-

tion but the crude reaction residue was pure enough to

allow complete analytical and spectroscopic characteriza-

tion.

As commented previously, we propose a sequential mech-

anism for this transformation with two clearly differentiated

steps (Scheme 1): A Norrish type II photoelimination of the

a-diketone that opens the pyranose ring leading to the acy-

clic photoenol II, which subsequently undergoes an intramo-

lecular aldol cyclization reaction. The photoelimination im-

plies an 1,5-HAT of the H8 by the excited innermost car-

bonyl of the a-diketone, followed by b-fragmentation of the

1,4-biradical intermediate I. The Norrish type II photoelimi-

nation, although very common in monoketones,^[1a]is ex-

tremely rare in a-diketones, in which only a few synthetical-

ly irrelevant examples are documented.^[29]This reaction has

been postulated to occur through a hydrogen abstraction by

the innermost carbonyl, which is otherwise completely un-

reactive from the photochemical point of view.^[30]

In addition, a number of octo-2,3-diuloses of the pentofur-

anose series of carbohydrates with d-ribo (70a and 71b)

and d-lyxo (72) stereochemistries were next synthesized to

study the influence of the furanose ring conformation in the

1,5-HAT reaction (Table 4). The photolysis of the d-ribo de-

rivative 70a led to the lactone 73 in moderate yield, pre-

sumably by oxidation of the photoenol intermediate 74a, as

previously observed in diketones 9 and 59 in which photo-

enolization competes with photoelimination.^[26]The most

populated conformer of 70a has a phase angle of P=2568

Table 4. Synthesis and photolysis of 2,3-diuloses with a-d-ribo- and a-d-

lyxofuranose stereochemistry.

a-C-Propynyl

Method^[b]2,3-Diulose

[%]^[a]

Product

[%]^[a]

glycoside [%]^[a]

67a (56)

68b (19)

B

70a (69)

71b (68)

73 (65)

73 (64)

The distance between the carbonyl oxygen and the g-hy-

drogen associated with the transition state of the 1,5-HAT

has been determined in monoketones to have a critical

value of around 2.7 ꢅ.^[31]It is not surprising, therefore, that

the hydrogen abstraction is strongly dependent on the pyra-

nose ring conformation of the a-C-glycoside: favored when

69 (81)

B

72 (39)

75^[c]

7

4

a C₄chair is adopted and highly disfavored in C₇arrange-

ments.

As far as we are aware, the uncatalyzed thermal syn aldol

cyclization in which a Z-photoenol (such as II, Scheme 1)

acts as a preformed enolate is an unprecedented process.^[32]

According to Baldwin rules^[33]the 5-(enolexo)-exo-trig ring

closure involved is stereoelectronically favored and may be

considered to be a new intramolecular carbonyl-ene cycliza-

tion, in which the carbonyl group and the enol can act as

74a

74b

[a] Yield of the product isolated by using chromatography. [b] Meth-

od B: NaIO₄(4 equiv), RuO₂·xH₂O (8.8 mg), CCl₄/CH₃CN/H₂O (1:1:1.5),

room temperature, dark. [c] The product was chromatographically unsta-

ble.

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E. I. Leon, E. Suꢄrez et al.

the major stereoisomer is that in which the two newly creat-

ed stereogenic centers are cis to each other. This is probably

very important for the overall yield of the reaction because

it permits the internal acetalization of the regenerated a-di-

ketone moiety avoiding secondary photolysis.^[40]

The steric influence of the adjacent substituents at C5 and

C7 in the stereochemical outcome can also be easily inferred

from these models (Figure 1). Interactions with the 5a-equa-

torial substituent in d-gluco (1, 18–24, Table 1), 6-deoxy-d-

gluco (39–40, Table 2), and 6,7-dideoxy-d-gluco (41–42,

Table 2) derivatives afforded exclusively OH-b-syn cycliza-

tions. The influence of this substituent is confirmed in the 5-

deoxy-d-gluco derivative (38), in which an equimolecular

mixture of OH-b-syn and OH-a-syn isomers was formed. In-

version of configuration at C5 in d-manno derivative (58)

entails a more crowded b-face of the transition-state (TS)

ring with exclusive formation of the OH-a-syn isomer. This

effect is also observed in d-galacto derivatives (59–61), thus

leading preferentially to a majority of OH-a-syn cyclization

products.

Scheme 4. Thermal kinetic studies with 50 and [D₁]50.

enophile and ene unit, respectively (Scheme 4).^[34]The rear-

rangement is accompanied by migration of the double bond

and a 1,5-shift of the enolic hydrogen.^[35]These thermal re-

actions, studied in detail with more stable deoxy-photoenols

50–52 (Scheme 3), proceeded with low activation energy

(40–608C). Comparatively, the uncatalyzed carbonyl-ene

processes usually require much higher temperatures.^[36]Sur-

prisingly, the cyclization temperature may be even lower in

more substituted pyranose frameworks; for example, perme-

thylated diketone 1 was transformed into 2 by irradiation at

08C for 12 h in 55% yield. In contrast, the dideoxy photoen-

ol 51 is stable at room temperature and requires 608C for

complete cyclization. This striking steric acceleration effect

has been previously observed in an uncatalyzed ene reac-

tion.^[37]Mechanistic studies of the ene-reaction have demon-

strated that a large deuterium kinetic isotope effect (KIE;

k_H/k_D>2) indicates that the INHAT is the rate-limiting step

and has often been taken as evidence of a concerted mecha-

nism.^[38]Taking advantage of the ready deuteration of the

photoenol, we decided to determine the intramolecular hy-

drogen–deuterium isotope effect for the thermal reaction of

photoenol 50 (Scheme 4). Photoenol 50 was chosen because

its cyclization into product 47 proceeded smoothly at a mod-

erate temperature and rate. The value of the reaction rate

constants for undeuterated 50 (k_H) and deuterated [D₁]50

(k_D) were measured by scanning at regular intervals

[D₆]benzene dissolved samples placed in a preheated (408C)

NMR probe and monitoring integral data for the vinylic

proton. The value of KIE obtained (k_H/k_D=3.7) appears to

indicate a concerted pericylic mechanism.

Degradation of the masked a-diketones could be realized

under oxidative conditions by using two different methodol-

ogies: With periodic acid in methanol (Method A)^[41]or by

b-fragmentation of the alkoxyl radical, generated from the

hemiketal alcohol by reaction with the PhIACHTUNRGTNEUNG(OAc)₂/I₂system

(Method B)^[42]as depicted in Table 5. With method A the

yields were excellent with substrates bearing very stable pro-

tective groups (e.g., methyl ethers, Table 5, entries 1 and 4)

but decreased substantially with easily oxidized (e.g., benzyl

ethers, entry 2) or acid-sensitive groups (e.g., silyl ethers, en-

tries 3 and 7). Method B, however, turned out to be more ef-

ficient with substrates possessing these sensitive groups, for

example, disilyl compound 47 (Table 5, entry 7). The effi-

ciency of both methods is similar with stable protective

groups (entry 5). Another observation that emerges from

these experiments is that methylation with diazomethane,

either of the crude or purified acid, considerably decreases

the global yield (compare method A, Table 5, entries 4 and

5 or method B, entries 6 and 7).

Models accounting for the

observed relative stereochemis-

try invoke the intermediacy of

a Z enolate, intramolecular hy-

drogen-bonding between the

OH and the carbonyl, and a

Zimmerman–Traxler-type tran-

sition state, which has been fre-

quently used for catalytic intra-

molecular

aldol

reactions

(Figure 1).^[10,39]The presence of

this hydrogen bond is anticipat-

ed to confer additional stability

and may help to maintain the

five-membered transition state

in a prearranged conformation

for cyclization. As expected

Figure 1. Proposed models for the stereochemical course of the aldol reaction. The transition state (TS) of the

from the models of Figure 1, major isomer is highlighted.

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Synthesis of Polyhydroxylated Cyclopentitols

Table 5. Synthesis of cyclopentitols.

FULL PAPER

Entry Substrate

Method

[%]^[a,b]

Product

1

2

3

2: R=R¹=Me

25: R=R¹=Bn

A (85)^[c]

A (65)^[c]

76: R=R¹=Me

77: R=R¹=Bn

26: R=Bn, R¹=DPS A (42)^[c]

78: R=Bn, R¹=DPS

4

5

6

7

46: R=Me

47: R=DPS

A (90)

79: R=Me, R¹=H

A (67),^[c]B (69)^[c]80: R=Me, R¹=Me

B (82)

81: R=DPS, R¹=H

A (26),^[c]B (60)^[c]82: R=DPS, R¹=Me

[a] Method A: H₅IO₆·2H₂O, MeOH, room temperature; Method B: PhI-

ACHTUNGTRENNUNG(OAc)₂, I₂, hn, room temperature. [b] Yield of the product isolated by

using chromatography. [c] Methylation with diazomethane.

Scheme 6. Some initial experiments on the reactivity of cyclopentitols.

a) KOH, MeOH, room temperature, 24 h; b) PhSO₂Cl, Py, 08C, 14 h,

73%, two-step; c) LiAlH₄, THF, 08C 4 h, 78%; d) KOH, MeOH, room

temperature, 24 h, then CH₂N₂, 99%; e) Tf₂O, CH₂Cl₂, Py, 08C, 24 h,

93%.

confirmed by dehydration to give the a,b-unsaturated ester

89. The b-lactone 87 was prepared also using acid 83 as

starting material, by treatment with benzenesulfonyl chlor-

ide in pyridine after hydrolysis of the acetyl group. The for-

mation of 87 confirms that it does indeed possess the syn-

hydroxy carboxylate arrangement generated during the

aldol reaction. Finally, the reduction of 83 with an excess of

LiAlH₄afforded the diol 88 spectroscopically identical to

the one synthesized by Chiara et al.^[43]

Conclusion

Scheme 5. Synthesis of cyclopentitols from 2,3-diuloses in a one-pot,

three-step sequence. a) Daylight-lamp irradiation, C₆D₆, 308C, 4 h, then

H₅IO₆·2H₂O, MeOH, room temperature, 3 h; b) daylight-lamp irradia-

The new sequential reaction described herein results in the

direct formation of densely polyfunctionalized cyclopentitols

by ring contraction of hexopyranose carbohydrates. It is

worth noting that the reaction proceeds efficiently in a one-

pot two-step process with no reagents other than light and

heat. The easy accessibility of pyranose sugars of various

configurations and the possibility of prior structural modifi-

cations illustrate the potential of this methodology for the

preparation of chiral synthons of cyclopentanoid natural

products. To the best of our knowledge, this is the first syn-

thetic application of the Norrish type II photoelimination in-

itiated by the innermost carbonyl of a a-diketone. The im-

portance of this reaction is that it uniquely generates an acy-

clic keto–enol system, which is ideally suited for a subse-

quent 5-(enolexo)-exo-trig intramolecular aldol cyclization.

This thermal uncatalyzed aldol reaction in which a Z photo-

enol acts as a preformed enolate is also unprecedented. The

stereochemistry of the cyclization is strongly dependent on

the configuration of the sugar-ring substituents; for example,

tion, C₆D₆, 36–408C, 2.5 h, then PhIACTHNUGTRNEG(UN OAc)₂, I₂, hn, room temperature,

40 min; c) daylight-lamp irradiation, C₆D₆, 36–408C, 5 h, then

H₅IO₆·2H₂O, MeOH, room temperature, 3 h. Product isolated by using

silica gel chromatography over three steps.

Another set of experiments in which the crude residue of

the photolysis–heating reaction is directly treated with the

oxidant reagents is summarized in Scheme 5. a-Diketones

18, 22, and 42 were converted into pure cyclopentanes 83–

85, respectively, in good overall yield by using this one-pot,

three-step process.

To confirm the structure of the cyclopentane derivatives

and to obtain information on their chemical reactivity, a

series of short chemical transformations were performed

(Scheme 6). The hydrolysis and subsequent methylation

with diazomethane of the previously prepared acid 83 af-

forded the a-hydroxyester 86 whose relative disposition was

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E. I. Leon, E. Suꢄrez et al.

(CH), 77.8 (C), 78.8 (CH), 80.4 (CH), 84.1 ppm (CH); IR (film): n˜ =

3254, 2933, 2112 cm^ꢁ1; MS (EI): m/z (%): 244 (<1) [M⁺], 199 (7);

HRMS (EI): m/z calcd for C₁₂H₂₀O₅: 244.1311 [M⁺]; found: 244.1306; el-

emental analysis calcd (%) for C₁₂H₂₀O₅(244.28): C 59.00, H 8.25; found:

C 59.14, H 8.37.

a d-gluco arrangement of the starting material leads exclu-

sively to OH-b-syn products, whereas an inverted OH-a-syn

cyclization is observed for the d-manno series of carbohy-

drates.

2,6-Anhydro-7,8-dideoxy-1,3,4,5-tetra-O-methyl-8-phenyl-d-glycero-l-

gulo-oct-7-ynitol (8): Compound 6 (310 mg, 1.27 mmol) in piperidine

(7 mL) was added to a suspension of [PdACTHNUTRGNEUNG(PPh₃)₄] (73 mg, 0.06 mmol),

Experimental Section

CuI (24 mg, 0.13 mmol), and PhI (140 mL, 1.27 mmol) in piperidine

(12 mL) at room temperature under nitrogen. The mixture was stirred at

808C for 1 h, diluted with EtOAc, washed with an aqueous saturated sol-

ution of NH₄Cl, and the organic layer dried and concentrated under re-

duced pressure. The residue was purified by silica gel column chromatog-

raphy (hexanes/EtOAc 7:3) to give 8 (359 mg, 1.12 mmol, 88%) as a yel-

lowish oil: [a]_D= +183 cm³g^ꢁ1dm^ꢁ1(c=2.15 in CHCl₃); ¹H NMR

(500 MHz, CDCl₃): d=3.31 (dd, J=9.8, 9.2 Hz, 1H), 3.33 (dd, J=9.5,

5.6 Hz, 1H), 3.40 (s, 3H), 3.51 (s, 3H), 3.53 (dd, J=9.3, 9.3 Hz, 1H), 3.55

(s, 3H), 3.606 (d, J=2.3 Hz, 1H), 3.61 (d, J=4.2 Hz, 1H), 3.65 (s, 3H),

3.91 (ddd, J=9.8, 3.9, 2.3 Hz, 1H), 5.06 (d, J=5.6 Hz, 1H), 7.30 (m, 3H),

7.46 ppm (m, 2H); ¹³C NMR (100.6 MHz, CDCl₃): d=59.0 (CH₃), 59.6

(CH₃), 60.8 (CH₃), 61.1 (CH₃), 67.0 (CH), 71.7 (CH₂), 73.8 (CH), 79.7

(CH), 81.4 (CH), 83.9 (C), 84.9 (CH), 89.7 (C), 122.7 (C), 128.5 (2ꢆCH),

128.9 (CH), 132.4 ppm (2ꢆCH); IR (film): n˜ =2931, 2226, 1100 cm^ꢁ1; MS

(EI): m/z (%): 305 (<1) [M⁺ꢁMe], 288 (4); HRMS (EI): m/z calcd for

C₁₇H₂₁O₅: 305.1389 [M⁺ꢁMe]; found: 305.1396; elemental analysis calcd

(%) for C₁₈H₂₄O₅(320.38): C 67.48, H 7.55; found: C 67.52, H 7.79.

General procedure for the oxidation of C-propynyl glycosides to a-dike-

tones: Method A: A solution of C-propynyl glycoside (1 equiv) in dry

CH₂Cl₂(20 mL) was cooled to ꢁ788C, ozone was introduced into the sol-

ution and the reaction monitored by TLC. Then, nitrogen was bubbled

through the solution to expel excess of ozone, dimethyl sulfide (2–

10 equiv) was added and the mixture was gradually warmed to room tem-

perature and stirred at this temperature for the specified time in the

dark. The mixture was concentrated under reduced pressure to give a

yellow residue that, in most cases, can be purified by rapid silica gel chro-

matography (hexanes/EtOAc mixtures) on a column protected from light

with aluminum foil, although a significant loss of material was generally

observed.

Method B: NaIO₄(3–4 equiv) and RuO₂·xH₂O (3–12 mg) were added to

a

solution of C-propynyl glycoside (1 equiv) in CCl₄/CH₃CN/H₂O

(17 mL, 1:1:1.5) and the mixture stirred at room temperature for the

specified time in the dark. The mixture was diluted with CH₂Cl₂, dried

over anhydrous Na₂SO₄, filtered and concentrated under reduced pres-

sure. The residue can be purified by rapid silica gel chromatography

(hexanes/EtOAc mixtures) on a column protected from light with alumi-

num foil, although a significant loss of material was generally observed.

3,7-Anhydro-4,5,6,8-tetra-O-methyl-1-phenyl-d-glycero-d-ido-octos-2-

ulose (9): Prepared from 8 (82 mg, 0.25 mmol) following the general pro-

cedure (Method A) using dimethyl sulfide (40 mL, 0.54 mmol). The mix-

ture was stirred at room temperature in the dark for 6 h and concentrat-

ed under reduced pressure to give 9 (106 mg) that was unstable on silica

gel and alumina. Notwithstanding, the crude residue (yellow oil) was

2,6-Anhydro-7,8-dideoxy-1,3,4,5-tetra-O-methyl-8-(trimethylsilyl)-d-glyc-

ꢀ

ero-l-gulo-oct-7-ynitol (5): Bu₃SnC CTMS (1.49 g, 3.86 mmol) was

added to a solution of 3^[44](538 mg, 1.93 mmol) in dry CH₂Cl₂(8 mL)

containing oven-dried powdered 4 ꢅ molecular sieves (1.1 g) and stirred

at room temperature under nitrogen for 15 min. Trimethylsilyl trifluoro-

methanesulfonate (873 mL, 4.83 mmol) was then added dropwise and the

stirring continued for 3 h. The mixture was diluted with CH₂Cl₂(32 mL),

neutralized with Et₃N, and filtered through a Celite pad. The filtrated

was concentrated under reduced pressure and the residue dissolved in

EtOAc and washed with an aqueous saturated solution of KF. The organ-

ic layer was dried over Na₂SO₄and concentrated under reduced pressure.

The residue was purified by silica gel column chromatography (hex-

anes!hexanes/EtOAc 9:1) to give 5 (403 mg, 1.28 mmol, 66%) as an oil:

[a]_D= +130 cm³g^ꢁ1dm^ꢁ1(c=3.53 in CHCl₃); ¹H NMR (500 MHz,

CDCl₃): d=0.18 (s, 9H), 3.16 (dd, J=9.3, 9.8 Hz, 1H), 3.23 (dd, J=5.6,

9.5 Hz, 1H), 3.39 (s, 3H), 3.43 (dd, J=9.3, 9.3 Hz, 1H), 3.46 (s, 3H), 3.54

(s, 3H), 3.57 (dd, J=10.7, 2.3 Hz, 1H), 3.60 (dd, J=10.7, 3.7 Hz, 1H),

3.63 (s, 3H), 3.82 (ddd, J=10.1, 3.7, 2.3 Hz, 1H), 4.81 ppm (d, J=5.6 Hz,

1H); ¹³C NMR (100.6 MHz, CDCl₃): d=ꢁ0.1 (3ꢆCH₃), 58.5 (CH₃), 59.1

(CH₃), 60.4 (CH₃), 60.7 (CH₃), 66.5 (CH), 71.2 (CH₂), 73.1 (CH), 79.2

(CH), 80.7 (CH), 84.3 (CH), 94.8 (C), 99.7 ppm (C); IR (film): n˜ =2931,

2190, 844 cm^ꢁ1; MS (EI): m/z (%): 316 (<1) [M⁺], 301 (<1); HRMS

(EI): m/z: calcd for C₁₅H₂₈O₅Si: 316.1706 [M⁺]; found 316.1701; elemen-

tal analysis calcd (%) for C₁₅H₂₈O₅Si (316.46): C 56.93, H 8.92; found: C

56.92, H 8.95.

1

pure enough to allow spectroscopic characterization. H NMR (500 MHz,

CDCl₃): d=2.86 (s, 3H), 3.22 (s, 3H), 3.34 (s, 3H), 3.39–3.45 (m, 2H),

3.44 (s, 3H), 3.50 (dd, J=8.6, 8.2 Hz, 1H), 3.64 (m, 2H), 4.65 (ddd, J=

9.7, 2.6, 2.6 Hz, 1H), 5.67 (d, J=7.4 Hz, 1H), 6.96 (m, 2H), 7.07 (m, 1H),

7.98 ppm (m, 2H); ¹³C NMR (100.6 MHz, CDCl₃): d=58.5 (CH₃), 59.0

(CH₃), 59.9 (CH₃), 60.1 (CH₃), 71.8 (CH₂), 74.7 (CH), 75.5 (CH), 79.2

(CH), 81.3 (CH), 84.2 (CH), 128.7 (CH), 130.3 (2ꢆCH), 133.1 (C), 133.9

(2ꢆCH), 190.8 (C), 203.7 ppm (C); IR (film): n˜ =1716, 1672, 1450 cm^ꢁ1

;

MS (EI): m/z (%): 352 (2) [M⁺], 247 (4), 219 (18); HRMS (EI): m/z

calcd for C₁₈H₂₄O₇: 352.1522 [M⁺]; found: 352.1527.

Photolysis of 9: A deoxygenated solution of crude diketone 9 (106 mg) in

dry C₆D₆(0.7 mL) was placed in a resonance tube and irradiated with a

daylight-lamp at 308C. The reaction was monitored by ¹H NMR spectro-

scopy, and complete consumption of starting material was observed after

9 h, leading to exclusive formation of intermediate photoenol III. The

solution could be concentrated at low temperature under reduced pres-

sure but the photoenol was not stable enough to withstand chromato-

graphic purification (silica gel or alumina). After silica gel column chro-

matography (hexanes/EtOAc, 75:25) only the known lactone 10^[45]

(28 mg, 0.12 mmol, 48% from 8) could be obtained.

4,8-Anhydro-1-deoxy-5,6,7,9-tetra-O-methyl-d-glycero-d-ido-nono-2,3-

diulose (1): Prepared from 7 (69 mg, 0.27 mmol) following the general

procedure (Method A) using dimethyl sulfide (40 mL, 0.54 mmol). The

mixture was stirred at room temperature in the dark for 6 h and concen-

trated under reduced pressure to give 1 (80 mg), which was unstable on

silica gel and alumina. Notwithstanding, the crude residue (yellow oil)

was pure enough to allow spectroscopic characterization. ¹H NMR

(400 MHz, CDCl₃): d=2.25 (s, 3H), 3.16 (dd, J=9.8, 7.7 Hz, 1H), 3.29

(dd, J=8.2, 7.7 Hz, 1H), 3.35 (s, 3H), 3.37 (s, 3H), 3.49 (s, 3H), 3.51 (dd,

J=10.6, 4.1 Hz, 1H), 3.55 (s, 3H), 3.59 (dd, J=10.6, 2.4 Hz, 1H), 3.64

(dd, J=7.9, 7.4 Hz, 1H), 4.18 (ddd, J=9.8, 4.2, 2.1 Hz, 1H), 5.48 ppm (d,

J=7.4 Hz, 1H); ¹³C NMR (100.6 MHz, CDCl₃): d=23.3 (CH₃), 59.1

(CH₃), 59.2 (CH₃), 59.8 (CH₃), 60.1 (CH₃), 71.5 (CH₂), 72.3 (CH), 74.1

(CH), 78.5 (CH), 80.6 (CH), 82.7 (CH), 197.1 (C), 200.3 ppm (C); IR

(film): n˜ =2934, 2933, 1715 cm^ꢁ1; MS (EI): m/z (%): 290 (<1) [M⁺], 247

2,6-Anhydro-7,8-dideoxy-1,3,4,5-tetra-O-methyl-d-glycero-l-gulo-oct-7-

ynitol (6): NaOH (1n, 3.9 mL) was added to a solution of 5 (652 mg,

2.06 mmol) in CH₂Cl₂/MeOH (5:1, 72 mL). The mixture was stirred at

room temperature for 2 h, neutralized with a solution of HCl 1n and ex-

tracted with EtOAc. The organic layer was washed with brine, dried over

Na₂SO₄, and concentrated under reduced pressure. The residue was puri-

fied by silica gel column chromatography (hexanes/EtOAc 70:30) to give

6 (462 mg, 1.89 mmol, 92%) as an oil: [a]_D= +132 cm³g^ꢁ1dm^ꢁ1(c=1.64

1

in CHCl₃); H NMR (500 MHz, CDCl₃): d=2.58 (d, J=9.3 Hz, 1H), 3.16

(dd, J=10.1, 9.0 Hz, 1H), 3.25 (dd, J=9.5, 5.9 Hz, 1H), 3.39 (s, 3H), 3.47

(dd, J=9.3, 9.2 Hz, 1H), 3.51 (s, 3H), 3.54 (s, 3H), 3.59 (d, J=3.4 Hz,

2H), 3.64 (s, 3H), 3.83 (ddd, J=10.1, 3.0, 3.0 Hz, 1H), 4.84 ppm (dd, J=

5.6, 2.3 Hz, 1H); ¹³C NMR (100.6 MHz, CDCl₃): d=58.4 (CH₃), 58.8

(CH₃), 60.1 (CH₃), 60.4 (CH₃), 65.6 (CH), 70.9 (CH), 73.1 (CH₂), 77.3

&

10

&

www.chemeurj.org

ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 0000, 00, 0 – 0

ÝÝ

These are not the final page numbers!

Synthesis of Polyhydroxylated Cyclopentitols

FULL PAPER

(2); HRMS (EI): m/z calcd for C₁₃H₂₂O₇: 290.1366 [M⁺]; found:

gel column chromatography (hexanes/EtOAc 9:1), to give

290.1363.

(2S,3aS,4S,5R,6S,6aR)-4,5,6-tris(benzyloxy)-6a-[(benzyloxy)methyl]-2-hy-

droxy-2-methyltetrahydro-2H-cyclopenta[b]furan-3

G

(25)

Photocyclization of 1: A solution of crude diketone 1 (80 mg) in dry

C₆D₆(1 mL), was placed in a resonance tube and irradiated with a day-

light lamp at 308C for 3 h. The mixture was concentrated under reduced

pressure and the residue purified by silica gel column chromatography

(hexanes/EtOAc 7:3), to give (2S,3aS,4S,5R,6S,6aR)-2-hydroxy-4,5,6-tri-

methoxy-6a-(methoxymethyl)-2-methyltetrahydro-2H-cyclopenta[b]fur-

(17 mg, 0.029 mmol, 58%) as a colorless oil: [a]_D= +31 cm³g^ꢁ1dm^ꢁ1(c=

0.9 in CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=1.37 (s, 3H), 3.21 (m,

1H), 3.77 (d, J=10.6 Hz, 1H), 3.89 (d, J=10.6 Hz, 1H), 3.94 (m, 1H),

4.00 (m, 2H), 4.57–4.76 (m, 8H), 5.09 (s, 1H), 7.23–7.39 ppm (m, 20H);

¹³C NMR (100.6 MHz, CDCl₃): d=20.6 (CH₃), 51.6 (CH), 71.8 (CH₂),

72.0 (CH₂), 72.6 (CH₂), 73.3 (CH₂), 74.3 (CH₂), 82.6 (CH), 85.0 (CH),

87.7 (C), 88.5 (CH), 99.2 (C), 127.7–128.8 (20ꢆCH), 135.9 (C), 137.5 (C),

an-3ACHTUNGTRENNUNG(3aH)-one (2) (41 mg, 0.14 mmol, 52% from 7) as a crystalline solid.

M.p. 96.6–97.28C (n-hexane/EtOAc); [a]_D= +138 cm³g^ꢁ1dm^ꢁ1(c=1.22

in CHCl₃); ¹H NMR (500 MHz, C₆D₆; note: the hydrogen atoms at C5

and C6 have very similar chemical shifts and as a consequence the cou-

pled hydrogen at C4 appears as a complex signal by virtual coupling. The

data of hydrogens at C4–C6 shown below have been calculated by itera-

tive simulation using program DAISY as implemented in Bruker Topspin

v. 2.1): d=1.64 (d, J=0.9 Hz, 3H), 2.73 (s, 3H), 3.09 (d, J=4.7 Hz, 1H),

3.17 (s, 3H), 3.25 (s, 6H), 3.30 (d, J=10.6 Hz, 1H), 3.49 (d, J=10.3 Hz,

1H), 3.64 (complex signal, d, J=8.2 Hz, 1H), 3.65 (complex signal, dd,

J=8.2, 6.3 Hz, 1H), 3.78 (complex signal, dd, J=6.3, 4.7 Hz, 1H),

5.21 ppm (d, J=0.6 Hz, 1H, OH); ¹H NMR (500 MHz, CDCl₃): d=1.41

(d, J=0.9 Hz, 3H), 3.08 (d, J=4.1 Hz, 1H), 3.42 (s, 3H), 3.46 (s, 3H),

3.48 (s, 3H), 3.50 (s, 3H), 3.58 (d, J=10.4 Hz, 1H), 3.63 (dd, J=6.1,

1.2 Hz, 1H), 3.68 (dd, J=6.0, 5.0 Hz, 1H), 3.70 (ddd, J=5.0, 4.2, 0.9 Hz,

1H), 3.71 (d, J=10.4 Hz, 1H), 5.05 ppm (brd, J=0.9 Hz, 1H, OH);

¹³C NMR (100.6 MHz, C₆D₆): d=21.1 (CH₃), 51.2 (CH), 57.5 (CH₃), 58.1

(CH₃), 58.7 (CH₃), 59.0 (CH₃), 74.2 (CH₂), 84.2 (CH), 87.6 (C), 88.4

(CH), 90.8 (CH), 99.7 (C), 208.1 ppm (C); IR (film): n˜ =3337, 2949, 2836,

1760 cm^ꢁ1; MS (FAB): m/z (%): 290 (2) [M⁺], 273 (100); HRMS (FAB):

m/z: calcd for C₁₃H₂₂O₇: 290.1366 [M⁺]; found: 290.1372; elemental anal-

ysis calcd (%) for C₁₃H₂₂O₇(290.31): C 53.78, H 7.64; found: C 53.71; H

7.73. Crystal data and structure refinement for compound 2: C₁₃H₂₂O₇,

M_t=290.31, orthorhombic, space group P2₁2₁2₁, a=7.9261(6) ꢅ, b=

137.6 (C), 137.8 (C), 208.3 ppm (C); IR (film): n˜ =3370, 2918, 1762 cm^ꢁ1

;

MS (EI): m/z (%): 594 (<1) [M⁺], 576 (<1); HRMS (EI): m/z calcd for

C₃₇H₃₈O₇: 594.2618 [M⁺]; found: 594.2615; elemental analysis calcd (%)

for C₃₇H₃₈O₇(594.69): C 74.73, H 6.44; found: C 74.37, H 6.83.

4,8-Anhydro-5,6,7-tri-O-benzyl-9-O-(tert-butyldiphenylsilyl)-1-deoxy-d-

glycero-d-ido-nono-2,3-diulose (19): Prepared from 12 (30 mg,

0.042 mmol) following the general procedure (Method B) using NaIO₄

(36 mg, 0.168 mmol) and RuO₂·xH₂O (0.5 mg). The reaction mixture was

stirred at room temperature in the dark for 1 h. The residue was purified

by rapid silica gel column chromatography (hexanes/EtOAc 97:3) to give

19 (20 mg, 0.027 mmol, 64%) as a yellow oil: [a]_D= +36 cm³g^ꢁ1dm^ꢁ1

1

(c=1.87 in CHCl₃); H NMR (400 MHz, CDCl₃): d=1.07 (s, 9H), 2.09 (s,

3H), 3.81 (m, 2H), 3.92 (dd, J=11.7, 3.2 Hz, 1H), 3.95 (dd, J=11.7,

2.1 Hz, 1H), 4.01 (dd, J=8.5, 7.2 Hz, 1H), 4.31 (m, 1H), 4.58 (d, J=

10.9 Hz, 1H), 4.66 (d, J=10.4 Hz, 2H), 4.82 (s, 2H), 4.84 (d, J=11.1 Hz,

1H), 5.62 (d, J=7.4 Hz, 1H), 7.16–7.73 ppm (m, 25H); ¹³C NMR

(100.6 MHz, CDCl₃): d=19.3 (C), 23.6 (CH₃), 26.5 (3ꢆCH₃), 62.9 (CH₂),

72.1 (CH), 74.2 (CH₂), 74.7 (CH₂), 75.2 (CH₂), 75.9 (CH), 76.9 (CH), 79.1

(CH), 81.6 (CH), 127.6–135.8 (25ꢆCH), 133.2–138.2 (5ꢆC), 197.6 (C),

200.7 ppm (C); IR (film): n˜ =2928, 1713 cm^ꢁ1; MS (EI): m/z (%): 742

(<1) [M⁺], 685 (<1); HRMS (EI): m/z calcd for C₄₆H₅₀O₇Si: 742.3326

[M⁺]; found: 742.3345; elemental analysis calcd (%) for C₄₆H₅₀O₇Si

(742.97): C 74.36, H 6.78; found: C 74.52, H 6.98.

9.2758(8) ꢅ, c=19.6176(17) ꢅ, b=908, V=1442.3(2) ꢅ³, Z=4, 1_calcd

=

1.337 mgm^ꢁ3, m

ACHTUNGTRENNUNG(Mo_Ka)=0.71073 ꢅ, FACHTUGNTREN(NUNG 000)=624, T=123 (2) K, colorless

Photocyclization of 19: A deoxygenated solution of diketone 19 (40 mg,

0.054 mmol) in purified CDCl₃(1.4 mL), was placed in a resonance tube

and irradiated with a daylight lamp at room temperature for 3 h. The

mixture was concentrated under reduced pressure and the residue puri-

fied by silica gel column chromatography (hexanes/EtOAc 9:1) to give

(3aS,4S,5R,6S,6aR)-4,5,6-tris(benzyloxy)-6a-[(tert-butyldiphenylsilyl)oxy]-

crystal, 0.45ꢆ0.20ꢆ0.12 mm³, collected reflections 12479. The structure

was solved by direct method, all hydrogen atoms were refined anisotropi-

cally using full-matrix least-squared based F₂to give R₁=0.0415, wR₂=

0.0689 for 3028 independently observed reflections (jF_oj >2s

ACHTUNGTRENNUNG

191 parameters.

Irradiation with pyrene:

A solution of crude diketone 1

methyl-2-hydroxy-2-methyltetrahydro-2H-cyclopenta[b]furan-3ACHTUNGTRENNUNG(3aH)-one

0.048 mmol) and pyrene (126 mg, 0.624 mmol) in dry C₆D₆(1.2 mL), was

(26) as a mixture of isomers (26 mg, 0.035 mmol, d.r. 5:1, 65%) as a col-

orless oil. ¹H NMR (500 MHz, CDCl₃; complex spectrum, only clearly

distinguished signals are reported): d=major isomer 1.08 (s, 9H), 1.44 (s,

3H), 3.29 (d, J=4.5 Hz, 1H), 5.09 ppm (s, 1H); minor isomer 1.02 (s,

9H), 1.49 (s, 3H), 3.31 ppm (d, J=3.7 Hz, 1H); ¹³C NMR (100.6 MHz,

CDCl₃) (complex spectrum, only clearly distinguished signals are report-

ed): d (major isomer)=19.1 (C), 20.3 (CH₃), 26.8 (3ꢆCH₃), 50.9 (CH),

66.0 (CH₂), 88.8 (C), 99.1 (C), 207.8 ppm (C); d (minor isomer)=19.2

(C), 22.6 (CH₃), 26.8 (3ꢆCH₃), 53.4 (CH), 65.1 (CH₂), 88.8 (C), 100.1

(C), 210.7 ppm (C); IR (film): n˜ =3374, 2928, 1765 cm^ꢁ1; MS (ESI⁺):

m/z (%): 765 (100) [M⁺+Na]; HRMS (ESI⁺): m/z calcd for

C₄₆H₅₀NaO₇Si: 765.3224 [M⁺+Na]; found: 765.3226; elemental analysis

calcd (%) for C₄₆H₅₀O₇Si (742.97): C 74.36, H 6.78; found: C 74.66, H

6.57.

placed in a resonance tube and irradiated with a daylight lamp at 308C

1

for 12 h. No reaction was detected by using H NMR spectroscopy under

these conditions.

4,8-Anhydro-5,6,7,9-tetra-O-benzyl-1-deoxy-d-glycero-d-ido-nono-2,3-

diulose (18): Prepared from 11 (70 mg, 0.125 mmol) following the general

procedure (Method B) using NaIO₄(107 mg, 0.5 mmol) and RuO₂·xH₂O

(1.1 mg). The reaction mixture was stirred at room temperature in the

dark for 1 h. The residue was purified by rapid silica gel column chroma-

tography (hexanes/EtOAc 9:1) to give 18 (46 mg, 0.077 mmol, 62%) as a

yellow oil: [a]_D= +52 cm³g^ꢁ1dm^ꢁ1(c=0.65 in CHCl₃); ¹H NMR

(500 MHz, CDCl₃): d=2.07 (s, 3H), 3.61 (dd, J=9.8, 8.0 Hz, 1H), 3.64

(dd, J=10.9, 3.6 Hz, 1H), 3.67 (dd, J=10.9, 2.4 Hz, 1H), 3.73 (dd, J=8.3,

8.0 Hz, 1H), 3.99 (dd, J=8.3, 7.1 Hz, 1H), 4.37 (ddd, J=9.8, 3.6, 2.4 Hz,

1H), 4.45 (d, J=10.9 Hz, 1H), 4.46 (d, J=12.1 Hz, 1H), 4.49 (d, J=

10.9 Hz, 1H), 4.57 (d, J=11.6 Hz, 2H), 4.69 (d, J=10.9 Hz, 1H), 4.75 (s,

2H), 5.56 (d, J=7.4 Hz, 1H), 7.09–7.30 ppm (m, 20H); ¹³C NMR

(100.6 MHz, CDCl₃): d=23.5 (CH₃), 68.9 (CH₂), 72.4 (CH), 73.4 (CH₂),

74.0 (CH₂), 74.5 (CH₂), 74.6 (CH), 74.9 (CH₂), 77.1 (CH), 78.5 (CH), 81.2

(CH), 127.6–128.4 (20ꢆCH), 136.8 (C), 137.9 (C), 138.1 (C), 138.2 (C),

197.4 (C), 200.7 ppm (C); IR (film): n˜ =2928, 1721 cm^ꢁ1; MS (EI): m/z

(%): 594 (<1) [M⁺], 503 (2); HRMS (EI): m/z calcd for C₃₇H₃₈O₇:

594.2618 [M⁺]; found: 594.2622; elemental analysis calcd (%) for

C₃₇H₃₈O₇(594.69): C 74.73, H 6.44; found: C 74.80, H 6.29.

9-O-Acetyl-4,8-anhydro-5,6,7-tri-O-benzyl-1-deoxy-d-glycero-d-ido-nono-

2,3-diulose (20): Prepared from 13 (70 mg, 0.136 mmol) following the

general procedure (Method B) using NaIO₄(116 mg, 0.542 mmol) and

RuO₂·xH₂O (1.2 mg). The reaction mixture was stirred at room tempera-

ture in the dark for 45 min. The residue was purified by rapid silica gel

column chromatography (hexanes/EtOAc 9:1) to give 20 (35 mg,

0.064 mmol, 47%) as a yellow oil: [a]_D= +89 cm³g^ꢁ1dm^ꢁ1(c=0.62 in

CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=2.05 (s, 3H), 2.12 (s, 3H), 3.49

(dd, J=9.8, 7.2 Hz, 1H), 3.80 (dd, J=7.9, 7.2 Hz, 1H), 4.07 (dd, J=7.8,

7.2 Hz, 1H), 4.21 (dd, J=12.2, 4.8 Hz, 1H), 4.33 (dd, J=12.2, 2.1 Hz,

1H), 4.45 (ddd, J=9.8, 4.8, 2.1 Hz, 1H), 4.503 (d, J=10.6 Hz, 1H), 4.506

(d, J=11.1 Hz, 1H), 4.59 (d, J=10.6 Hz, 1H), 4.74 (d, J=10.9 Hz, 1H),

4.76 (d, J=11.4 Hz, 1H), 4.81 (d, J=11.3 Hz, 1H), 5.57 (d, J=7.2 Hz,

1H), 7.10–7.35 ppm (m, 15H); ¹³C NMR (100.6 MHz, CDCl₃): d=20.8

Photocyclization of 18: A deoxygenated solution of diketone 18 (30 mg,

0.05 mmol) in purified CDCl₃(0.6 mL), was placed in a resonance tube

and irradiated with a daylight lamp at 308C for 2 h. The mixture was con-

centrated under reduced pressure and the residue was purified by silica

Chem. Eur. J. 2013, 00, 0 – 0

ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

&

11

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ÞÞ

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E. I. Leon, E. Suꢄrez et al.

(CH₃), 23.5 (CH₃), 63.4 (CH₂), 72.6 (CH), 72.9 (CH), 73.9 (CH₂), 74.1

(CH₂), 74.6 (CH₂), 76.8 (CH), 78.1 (CH), 80.2 (CH), 127.8–128.5 (15ꢆ

CH), 136.7 (C), 137.6 (C), 137.9 (C), 170.8 (C), 197.2 (C), 199.6 ppm (C);

IR (film): n˜ =2928, 1735 cm^ꢁ1; MS (EI): m/z (%): 546 (2) [M⁺], 475 (1);

HRMS (EI): m/z calcd for C₃₂H₃₄O₈: 546.2254 [M⁺]; found: 546.2236; el-

emental analysis calcd (%) for C₃₂H₃₄O₈(546.61): C 70.31, H 6.27; found:

C 70.34, H 6.27.

4,8-Anhydro-1-deoxy-5,6-di-O-methyl-7,9-O-isopropylidene-d-glycero-d-

ido-nono-2,3-diulose (22): Prepared from 15 (136.0 mg, 0.50 mmol) fol-

lowing the general procedure (Method A) using dimethyl sulfide (400 mL,

5.4 mmol). The mixture was stirred at room temperature in the dark for

3.5 h and concentrated under reduced pressure. The residue was purified

by rapid silica gel column chromatography (hexanes/EtOAc 8:2) to give

22 (102.2 mg, 0.34 mmol, 67%) as a yellow oil: [a]_D= +107 cm³g^ꢁ1dm^ꢁ1

1

(c=0.58 in CHCl₃); H NMR (500 MHz, CDCl₃): d=1.40 (s, 3H), 1.48 (s,

Photocyclization of 20: A deoxygenated solution of diketone 20 (35 mg,

0.064 mmol) in purified CDCl₃(1 mL), was placed in a resonance tube

and irradiated with a daylight lamp at 308C for 1 h. The mixture was con-

centrated under reduced pressure and the residue purified by silica gel

column chromatography (hexanes/EtOAc 8:2) to give (3aS,4S,5R,6-

S,6aR)-4,5,6-tris(benzyloxy)-6a-(acetyloxy)methyl-2-hydroxy-2-methylte-

3H), 2.28 (s, 3H), 3.34 (dd, J=8.7, 8.6 Hz, 1H), 3.41 (s, 3H), 3.50 (m,

1H), 3.55 (s, 3H), 3.58–3.63 (m, 2H), 3.92 (dd, J=10.7, 5.3 Hz, 1H), 4.13

(ddd, J=10.1, 10.1, 5.3 Hz, 1H), 5.51 ppm (d, J=7.6 Hz, 1H); ¹³C NMR

(125.7 MHz, CDCl₃): d=19.0 (CH₃), 23.4 (CH₃), 29.0 (CH₃), 60.0 (CH₃),

60.3 (CH₃), 62.5 (CH₂), 67.3 (CH), 71.9 (CH), 74.0 (CH), 81.1 (CH), 81.2

(CH), 99.3 (C), 197.2 (C), 200.3 ppm (C); IR (CHCl₃, 0.2 mm): n˜ =2999,

1713 cm^ꢁ1; MS (ESI⁺): m/z (%): 357 (100) [M⁺+MeOH+Na]; HRMS

(ESI⁺): m/z calcd for C₁₅H₂₆NaO₈: 357.1525 [M⁺+MeOH+Na]; found:

357.1526; elemental analysis calcd (%) for C₁₄H₂₂O₇(302.32): C 55.62, H

7.33; found: C 55.57, H 7.34.

trahydro-2H-cyclopenta[b]furan-3ACTHNUTRGENUGN(3aH)-one (27) a colorless oil as a mix-

ture of isomers (23.5 mg, 0.043 mmol, d.r., 1:0.9, 67%): ¹H NMR

(500 MHz, CDCl₃; complex spectrum, only clearly distinguished signals

are reported): d=1.35 (s, 3H), 1.42 (s, 3H), 2.03 (s, 3H), 2.09 (s, 3H),

3.07 (d, J=1.9 Hz, 1H), 3.11 (d, J=3.2 Hz, 1H), 3.92 ppm (d, J=5.4 Hz,

1H); ¹³C NMR (100.6 MHz, C₆D₆; complex spectrum, only clearly distin-

guished signals are reported): d=20.8 (CH₃), 20.9 (CH₃), 21.5 (CH₃), 22.5

(CH₃), 52.7 (CH), 54.9 (CH), 65.8 (CH₂), 65.9 (CH₂), 87.7 (CH), 87.9 (C),

88.7 (C), 99.3 (C), 100.0 (C), 170.3 (C), 170.4 (C), 206.6 (C), 210.3 ppm

(C); IR (film): n˜ =3424, 2927, 1742 cm^ꢁ1; MS (EI): m/z (%): 546 (<1)

[M⁺], 503 (<1); HRMS (EI): m/z calcd for C₃₂H₃₄O₈: 546.2254 [M⁺];

found: 546.2273; elemental analysis calcd (%) for C₃₂H₃₄O₈(546.61): C

70.31, H 6.27; found: C 70.10, H 6.40.

Photocyclization of 22 to compound 29: A solution of 22 (16.1 mg,

0.053 mmol) in dry C₆D₆(0.3 mL), was placed in a resonance tube and ir-

radiated with a daylight lamp at 36–408C for 2.5 h. The mixture was con-

centrated under reduced pressure and the residue purified by silica gel

column chromatography (hexanes/EtOAc 7:3) to give a mixture of hemi-

ketal diastereomers 29 (8.5 mg, 0.028 mmol, d.r. 10:3, 53%) (major

isomer:

(2S,3aS,4S,5R,5aS,9aR)-2-hydroxy-4,5-dimethoxy-2,7,7-

[1,2-d][1,3]dioxin-3(2H)-one)

trimethyltetrahydrofuro[2’,3’:2,3]cyclopenta

N

ACHTUNGTRENNUNG

as a colorless oil: [a]_D= +29 cm³g^ꢁ1dm^ꢁ1(c=0.50, CHCl₃); ¹H NMR

(500 MHz, CDCl₃;): d (major isomer)=1.36 (s, 3H), 1.47 (s, 3H), 1.48 (s,

3H), 2.99 (d, J=2.2 Hz, 1H), 3.30 (s, 3H), 3.42 (s, 3H), 3.76 (dd, J=1.6,

1.3 Hz, 1H), 3.89 (d, J=12.3 Hz, 1H), 3.92 (ddd, J=2.2, 1.6, 1.3 Hz, 1H),

4.05 (d, J=12.3 Hz, 1H), 4.11 ppm (dd, J=1.3, 1.3 Hz, 1H); ¹³C NMR

(125.7 MHz, CDCl₃): d (major isomer)=22.3 (CH₃), 22.8 (CH₃), 25.5

(CH₃), 54.9 (CH), 56.0 (CH₃), 57.2 (CH₃), 66.4 (CH₂), 79.0 (CH), 87.9

(CH), 88.0 (C), 88.8 (CH), 99.7 (C), 99.8 (C), 210.8 ppm (C); IR (CHCl₃,

0.2 mm): n˜ =3581, 3016, 1770 cm^ꢁ1; MS (ESI⁺): m/z (%): 325 (100) [M⁺

+Na]; HRMS (ESI⁺): m/z calcd for C₁₄H₂₂NaO₇: 325.1263 [M⁺+Na];

found: 325.1252; elemental analysis calcd (%) for C₁₄H₂₂O₇(302.32): C

55.62, H 7.33; found: C 55.73, H 7.00.

4,8-Anhydro-9-azido-5,6,7-tri-O-benzyl-1,9-dideoxy-d-glycero-d-ido-

nono-2,3-diulose (21): Prepared from 14 (60 mg, 0.121 mmol) following

the general procedure (Method B) using NaIO₄(103 mg, 0.481 mmol)

and RuO₂·xH₂O (1.1 mg). The reaction mixture was stirred at room tem-

perature in the dark for 30 min. The residue was purified by rapid silica

gel column chromatography (hexanes/EtOAc 1:1) to give 21 (38 mg,

0.072 mmol, 59%) as a yellow oil. [a]_D= +52 cm³g^ꢁ1dm^ꢁ1(c=2.32 in

CHCl₃); ¹H NMR (400 MHz, CDCl₃): d=2.12 (s, 3H), 3.34 (dd, J=13.3,

5.0 Hz, 1H), 3.51 (dd, J=9.8, 7.2 Hz, 1H), 3.55 (dd, J=13.3, 2.4 Hz, 1H),

3.77 (dd, J=8.0, 7.4 Hz, 1H), 4.08 (dd, J=8.2, 7.4 Hz, 1H), 4.43 (ddd, J=

9.7, 4.6, 2.1 Hz, 1H), 4.50–4.82 (m, 6H), 5.60 (d, J=7.2 Hz, 1H), 7.18–

7.37 ppm (m, 15H); ¹³C NMR (100.6 MHz, CDCl₃): d=23.5 (CH₃), 51.7

(CH₂), 72.6 (CH), 74.0 (CH), 74.1 (CH₂), 74.3 (CH₂), 74.7 (CH₂), 77.7

(CH), 78.2 (CH), 80.2 (CH), 127.8–128.6 (15ꢆCH), 136.7 (C), 137.7 (C),

137.9 (C), 197.2 (C), 199.8 ppm (C); IR (film): n˜ =2925, 2099, 1731,

1715 cm^ꢁ1; MS (ESI⁺): m/z (%): 584 (100) [M⁺+MeOH+Na]; HRMS

(ESI⁺): m/z calcd for C₃₁H₃₅N₃NaO₇: 584.2373 [M⁺+MeOH+Na];

found: 584.2372. All attempts at obtaining correct elemental analysis for

this azide in two different analyzers failed.

4,8-Anhydro-7,9-bis-O-(tert-butyldimethylsilyl)-1-deoxy-5,6-di-O-methyl-

d-glycero-d-ido-nono-2,3-diulose (23): Prepared from 16 (51 mg,

0.12 mmol) following the general procedure (Method A) using dimethyl

sulfide (15 mL, 0.2 mmol). The mixture was stirred at room temperature

in the dark for 2 h and concentrated under reduced pressure. The residue

was purified by rapid silica gel column chromatography (hexanes/EtOAc

1:1) to give 23 (40 mg, 0.09 mmol, 75%) as a yellow oil: [a]_D= +

1

74 cm³g^ꢁ1dm^ꢁ1(c=0.82 in CHCl₃); H NMR (500 MHz, CDCl₃): d=0.02

Photocyclization of 21: A deoxygenated solution of diketone 21 (31 mg,

0.059 mmol) in purified CDCl₃(1.0 mL), was irradiated with a daylight

lamp at 308C for 2 h. The solution was concentrated under reduced pres-

sure and the residue purified by Chromatotron chromatography (Al₂O₃,

hexanes/EtOAc 8:2) to give the isomeric mixture (3aS,4S,5R,6S,6aR)-6a-

(azidomethyl)-4,5,6-tris(benzyloxy)-2-hydroxy-2-methyltetrahydro-2H-cy-

(s, 3H), 0.03 (s, 3H), 0.09 (s, 3H), 0.10 (s, 3H), 0.87 (s, 9H), 0.88 (s, 9H),

2.29 (s, 3H), 3.17 (dd, J=8.5, 8.2 Hz, 1H), 3.38 (s, 3H), 3.51 (s, 3H), 3.55

(dd, J=8.5, 7.3 Hz, 1H), 3.58 (dd, J=9.1, 8.2 Hz, 1H), 3.75 (dd, J=11.7,

3.5 Hz, 1H), 3.81 (dd, J=11.7, 1.9 Hz, 1H), 4.02 (ddd, J=9.2, 3.4, 1.9 Hz,

1H), 5.47 ppm (d, J=7.2 Hz, 1H); ¹³C NMR (100.6 MHz, CDCl₃): d=

ꢁ5.4 (CH₃), ꢁ5.1 (CH₃), ꢁ5.0 (CH₃), ꢁ4.1 (CH₃), 18.1 (C), 18.4 (C), 23.5

(CH₃), 25.90 (3ꢆCH₃), 25.95 (3ꢆCH₃), 58.9 (CH₃), 60.6 (CH₃), 62.3

(CH₂), 69.2 (CH), 72.1 (CH), 77.1 (CH), 81.9 (CH), 83.9 (CH), 197.6 (C),

201.3 ppm (C); IR (film): n˜ =2955, 1711 cm^ꢁ1; MS (EI): m/z (%): 491 (1)

[M⁺+H], 433 (87); HRMS (EI): m/z calcd for C₂₃H₄₇O₇Si₂: 491.2860 [M⁺

+H]; found: 491.2875; elemental analysis calcd (%) for C₂₃H₄₆O₇Si₂

(490.78): C 56.29, H 9.45; found: C 56.30, H 9.45.

clopenta[b]furan-3ACHTUNGTRENNUNG(3aH)-one (28) (17 mg, 0.032 mmol, d.r. 1.3:1, 55%) as

a colorless oil: ¹H NMR (500 MHz, CDCl₃): d=1.36 (s, 3H), 1.49 (s,

3H), 3.09 (d, J=2.5 Hz, 1H), 3.12 (d, J=3.5 Hz, 1H), 3.46 (d, J=

13.6 Hz, 1H), 3.78 (d, J=10.6 Hz, 1H), 3.79 (d, J=13.2 Hz, 1H), 3.89 (d,

J=4.4 Hz, 1H), 3.90 (d, J=12.9 Hz, 1H), 3.97 (dd, J=3.8, 3.5 Hz, 1H),

3.99 (dd, J=5.4, 4.7 Hz, 1H), 4.07 (dd, J=3.8, 3.8 Hz, 1H), 4.18 (ddd, J=

3.5, 2.4, 1.1 Hz, 1H), 4.20 (d, J=4.1 Hz, 1H), 4.41–4.70 (m, 12H), 7.21–

7.38 ppm (m, 30H); ¹³C NMR (125.7 MHz, CDCl₃): d=21.3 (CH₃), 22.6

(CH₃), 52.8 (CH), 54.7 (CH₂), 54.7 (CH), 54.9 (CH₂), 71.6 (CH₂), 71.9

(CH₂), 72.3 (CH₂), 72.7 (CH₂), 73.2 (CH₂), 72.2 (CH₂), 82.5 (CH), 83.6

(CH), 85.1 (CH), 85.3 (CH), 87.9 (CH), 88.4 (C), 88.8 (CH), 90.1 (C),

99.4 (C), 100.3 (C), 127.8–128.7 (30ꢆCH), 136.3 (C), 137.2 (C), 137.3 (C),

137.39 (C), 137.41 (C), 137.5 (C), 207.0 (C), 210.1 ppm (C); IR (film): n˜ =

3414, 2105, 1767 cm^ꢁ1; MS (ESI⁺): m/z (%): 552 (100) [M⁺+Na]; HRMS

(ESI⁺): m/z calcd for C₃₀H₃₁N₃NaO₆: 552.2111 [M⁺+Na]; found:

552.2111. All attempts at obtaining a correct elemental analysis for this

azide in two different analyzers failed.

Photocyclization of 23: A solution of diketone 23 (28 mg, 0.057 mmol) in

purified CDCl₃(0.7 mL), was placed in a resonance tube and irradiated

with a daylight lamp at 308C for 3 h. The mixture was concentrated

under reduced pressure and the residue purified by Chromatotron chro-

matography (Al₂O₃, toluene as eluent) to give (2S,3aS,4S,5R,6S,6aR)-6-

[(tert-butyldimethylsilyl)oxy]-6a-[(tert-butyldimethylsilyl)oxy]methyl-2-hy-

droxy-4,5-dimethoxy-2-methyltetrahydro-2H-cyclopenta[b]furan-3ACHTUNGTRENNUNG(3aH)-

one (30) (17.5 mg, 0.036 mmol, 63%) as

a colorless oil: [a]_D= +

54 cm³g^ꢁ1dm^ꢁ1(c=2.10 in CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=

0.091 (s, 3H), 0.099 (s, 3H), 0.13 (s, 3H), 0.14 (s, 3H), 0.89 (s, 9H), 0.92

&

12

&

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Synthesis of Polyhydroxylated Cyclopentitols

FULL PAPER

(s, 9H), 1.39 (d, J=0.9 Hz, 3H), 2.95 (d, J=4.4 Hz, 1H), 3.39 (s, 3H),

3.43 (s, 3H), 3.53 (dd, J=5.4, 5.4 Hz, 1H), 3.69 (dd, J=5.0, 4.4 Hz, 1H),

3.77 (d, J=11.4 Hz, 1H), 3.85 (d, J=11.4 Hz, 1H), 3.99 (d, J=5.7 Hz,

1H), 5.11 ppm (d, J=0.9 Hz, 1H); ¹³C NMR (100.6 MHz, CDCl₃): d=

ꢁ5.7 (CH₃), ꢁ5.6 (CH₃), ꢁ5.1 (CH₃), ꢁ4.8 (CH₃), 18.0 (C), 18.4 (C), 20.3

(CH₃), 25.6 (3ꢆCH₃), 25.8 (3ꢆCH₃), 51.3 (CH), 57.6 (CH₃), 58.4 (CH₃),

65.9 (CH₂), 81.6 (CH), 72.1 (CH), 84.5 (CH), 89.4 (CH), 90.1 (CH), 98.7

(CH), 208.5 ppm (C); IR (film): n˜ =3368, 2931, 1765 cm^ꢁ1; MS (EI): m/z

(%): 473 (2) [M⁺ꢁOH], 433 (7); HRMS (EI): m/z calcd for C₂₃H₄₅O₆Si₂:

473.2755 [M⁺ꢁOH]; found: 473.2761; elemental analysis calcd (%) for

C₂₃H₄₆O₇Si₂(490.78): C 56.29, H 9.45; found: C 56.21, H 9.22.

CH), 133.8 (C), 134.0 (C), 198.9 (C), 199.9 ppm (C); IR (film): n˜ =2938,

1722 cm^ꢁ1; MS (ESI⁺): m/z (%): 539 (100) [M⁺+MeOH+Na]; HRMS

(ESI⁺): m/z calcd for C₂₈H₄₀NaO₇Si: 539.2441 [M⁺+MeOH+Na]; found:

539.2440; elemental analysis calcd (%) for C₂₇H₃₆O₆Si (484.66): C 66.91,

H 7.49; found: C 67.09, H 7.52.

Photocyclization of 38: A solution of diketone 38 (48 mg, 0.102 mmol) in

dry C₆D₆(1.0 mL), was placed in a resonance tube and irradiated with a

daylight lamp at 308C. The reaction was monitored by ¹H NMR spectro-

scopy, complete consumption of starting material was observed after 9 h.

Then, the reaction mixture was heated at 608C for 5 h and concentrated

under reduced pressure. The residue was solved in CH₂Cl₂(0.82 mL)

cooled to 08C and acetylated by adding Ac₂O (29 mL, 0.306 mmol) and

DMAP (37 mg, 0.306 mmol) followed by stirring at room temperature

for 2 h. The reaction mixture was concentrated under reduced pressure

and the residue partially resolved by silica gel column chromatography

(hexanes/EtOAc 8:2) to give (2R,3aS,5R,6S,6aR)-6a-[(tert-butyldiphenyl-

silyl)oxy]methyl-5,6-dimethoxy-2-methyl-3-oxohexahydro-2H-cyclopen-

ta[b]furan-2-yl acetate (44) and (2S,3aR,5R,6S,6aS)-6a-[(tert-butyldiphe-

nylsilyl)oxy]methyl-5,6-dimethoxy-2-methyl-3-oxohexahydro-2H-cyclo-

penta[b]furan-2-yl acetate (45) (21 mg, 0.040 mmol, d.r. 1:1, 39%). The

sensitive photoenol intermediate was detected by NMR spectroscopy but

in this case could not be obtained in pure state. Only clearly distinguish-

ed signals from the reaction mixture are reported: ¹H NMR (500 MHz,

C₆D₆): d=1.25 (s, 9H), 1.75 (s, 3H), 2.85 (s, 3H), 3.00 (s, 3H), 4.70 (d,

J=18.6 Hz, 1H), 4.82 (d, J=18.6 Hz, 1H), 5.28 (dd, J=7.5, 7.5 Hz, 1H),

6.66 ppm (br s, 1H, OH); ¹³C NMR (125.7 MHz, C₆D₆): d=19.6 (C), 22.3

(CH₃), 27.0 (3ꢆCH₃), 57.6 (CH₃), 59.3 (CH₃), 69.5 (CH₂), 111.6 (CH),

149.2 (C), 193.9 (C), 207.5 ppm (C).

Compound 44: colorless oil. [a]_D=ꢁ2 cm³g^ꢁ1dm^ꢁ1(c=0.54 in CHCl₃);

¹H NMR (500 MHz, CDCl₃): d=1.06 (s, 9H), 1.55 (s, 3H), 1.75 (s, 3H),

1.99 (dddd, J=13.9, 4.4, 4.4, 1.3 Hz, 1H), 2.30 (ddd, J=13.9, 10.4, 5.4 Hz,

1H), 3.23 (dd, J=10.4, 4.4 Hz, 1H), 3.27 (s, 3H), 3.47 (s, 3H), 3.73 (br d,

J=4.1 Hz, 1H), 3.85 (d, J=10.1 Hz, 1H), 3.88 (ddd, J=4.7, 4.7, 4.7 Hz,

1H), 3.91 (d, J=10.1 Hz, 1H), 7.36–7.79 ppm (m, 10H); ¹³C NMR

(100.6 MHz, CDCl₃): d=19.3 (C), 20.7 (CH₃), 23.0 (CH₃), 26.9 (3ꢆCH₃),

31.7 (CH₂), 46.4 (CH), 56.4 (CH₃), 58.9 (CH₃), 64.4 (CH₂), 82.7 (CH),

90.6 (CH), 93.1 (C), 101.9 (C), 127.6–135.8 (10ꢆCH), 133.42 (C), 133.45

(C), 169.5 (C), 209.7 ppm (C); IR (film): n˜ =2928, 1766, 1743 cm^ꢁ1; MS

(ESI⁺): m/z (%): 549 (100) [M⁺+Na]; HRMS (ESI⁺): m/z calcd for

C₂₉H₃₈NaO₇Si: 549.2285 [M⁺+Na]; found: 549.2285; elemental analysis

calcd (%) for C₂₉H₃₈O₇Si (526.69): C 66.13, H 7.27; found: C 66.40, H

7.61.

7-O-Acetyl-4,8-anhydro-9-O-(tert-butyldimethylsilyl)-1-deoxy-5,6-di-O-

methyl-d-glycero-d-ido-nono-2,3-diulose (24): Prepared from 17

(176.7 mg, 0.46 mmol) following the general procedure (Method A) using

dimethyl sulfide (267 mL, 3.64 mmol). The mixture was stirred at room

temperature in the dark for 2 h and concentrated under reduced pressure.

The residue was purified by rapid silica gel column chromatography (hex-

anes/EtOAc 1:1) to give 24 (139.0 mg, 0.33 mmol, 73%) as a yellow oil:

1

[a]_D= +76 cm³g^ꢁ1dm^ꢁ1(c=0.59 in CHCl₃); H NMR (500 MHz, CDCl₃):

d=0.02 (s, 6H), 0.87 (s, 9H), 2.06 (s, 3H), 2.30 (s, 3H), 3.35 (s, 3H), 3.46

(dd, J=6.8, 6.6 Hz, 1H), 3.50 (s, 3H), 3.65 (dd, J=11.4, 4.7 Hz, 1H), 3.74

(dd, J=11.4, 3.2 Hz, 1H), 3.80 (dd, J=6.8, 6.6 Hz, 1H), 4.16 (ddd, J=

8.8, 4.7, 3.2 Hz, 1H), 4.96 (dd, J=8.8, 6.6 Hz, 1H), 5.47 ppm (d, J=

6.6 Hz, 1H); ¹³C NMR (125.7 MHz, CDCl₃): d=ꢁ5.5 (2ꢆCH₃), 18.3 (C),

21.0 (CH₃), 23.5 (CH₃), 25.8 (3ꢆCH₃), 58.9 (CH₃), 59.6 (CH₃), 63.0

(CH₂), 68.8 (CH), 72.9 (CH), 74.6 (CH), 79.6 (2ꢆCH), 169.7 (C), 197.1

(C), 198.5 ppm (C); IR (CHCl₃, 0.2 mm): n˜ =2933, 1738, 1715 cm^ꢁ1; MS

(ESI⁺): m/z (%): 473 (100) [M⁺+MeOH+Na]; HRMS (ESI⁺): m/z calcd

for C₂₀H₃₈NaO₉Si: 473.2183 [M⁺+MeOH+Na]; found: 473.2182; elemen-

tal analysis calcd (%) for C₁₉H₃₄O₈Si (418.55): C 54.52, H 8.19; found: C

54.53, H 8.19.

Photocyclization of 24:

A deoxygenated solution of diketone 24

(41.1 mg, 0.098 mmol) in dry C₆D₆(0.3 mL), was placed in a resonance

tube and irradiated with a daylight lamp at 36–408C for 3 h. The solution

was concentrated under reduced pressure and the residue purified by

silica gel column chromatography (hexanes/EtOAc 7:3) to give a mixture

of hemiketal diastereomers 31 (25.4 mg, 0.061 mmol, d.r., 10:3, 62%)

(major isomer: (2S,3aS,4S,5R,6S,6aR)-6a-[(tert-butyldimethylsilyl)oxy]-

methyl-5-ethoxy-2-hydroxy-4-methoxy-2-methyl-3-oxohexahydro-2H-cy-

clopenta[b]furan-6-yl acetate) as a colorless oil: [a]_D= +56 cm³g^ꢁ1dm^ꢁ1

1

(c=0.59 in CHCl₃); H NMR (500 MHz, CDCl₃): d (major isomer)=0.15

(s, 6H), 0.92 (s, 9H), 1.40 (d, J=1.0 Hz, 3H), 2.08 (s, 3H), 3.11 (dd, J=

2.1, 0.9 Hz, 1H), 3.34 (s, 3H), 3.38 (s, 3H), 3.74 (ddd, J=2.3, 2.3, 0.8 Hz,

1H), 3.77 (d, J=10.7 Hz, 1H), 3.80 (d, J=10.7 Hz, 1H), 3.87 (ddd, J=

2.1, 2.1, 0.9 Hz, 1H), 4.91 (d, J=1.0 Hz, 1H), 5.21 ppm (dd, J=2.5,

1.0 Hz, 1H); ¹³C NMR (125.7 MHz, CDCl₃): d (major isomer)=ꢁ5.64

(CH₃), ꢁ5.55 (CH₃), 18.4 (C), 20.0 (CH₃), 20.8 (CH₃), 25.8 (3 ꢆ CH₃),

52.7 (CH), 57.2 (CH₃), 57.3 (CH₃), 64.7 (CH₂), 80.5 (CH), 86.46 (CH),

86.58 (CH), 90.7 (C), 98.7 (C), 169.6 (C), 207.0 ppm (C); IR (CHCl₃,

0.2 mm): n˜ =2933, 1766, 1742 cm^ꢁ1; MS (ESI⁺): m/z (%): 441 (100) [M⁺

+Na]; HRMS (ESI⁺): m/z calcd for C₁₉H₃₄NaO₈Si: 441.1921 [M⁺+Na];

found: 441.1920; elemental analysis calcd (%) for C₁₉H₃₄O₈Si (418.55): C

54.52, H 8.19; found: C 54.55, H 8.14.

Compound 45: colorless oil, [a]_D=ꢁ15 cm³g^ꢁ1dm^ꢁ1(c=0.56 in CHCl₃);

¹H NMR (500 MHz, CDCl₃): d=1.07 (s, 9H), 1.50 (s, 3H), 1.77 (ddd, J=

12.8, 9.8, 9.8 Hz, 1H), 1.86 (s, 3H), 2.27 (ddd, J=12.9, 6.3, 2.2 Hz, 1H),

3.31 (dd, J=10.1, 2.2 Hz, 1H), 3.35 (s, 3H), 3.46 (s, 3H), 3.49 (m, 1H),

3.77 (d, J=10.1 Hz, 1H), 3.85 (d, J=9.8 Hz, 1H), 3.92 (d, J=7.6 Hz,

1H), 7.36–7.69 ppm (m, 10H); ¹³C NMR (100.6 MHz, CDCl₃): d=19.3

(C), 20.5 (CH₃), 21.9 (CH₃), 26.9 (3ꢆCH₃), 30.4 (CH₂), 46.8 (CH), 57.5

(CH₃), 59.5 (CH₃), 65.4 (CH₂), 84.5 (CH), 84.8 (CH), 88.5 (C), 101.2 (C),

127.7–135.7 (10ꢆCH), 132.9 (C), 133.0 (C), 169.5 (C), 211.0 ppm (C); IR

(film): n˜ =2931, 1768, 1744 cm^ꢁ1; MS (ESI⁺): m/z (%): 549 (100) [M⁺

+Na]; HRMS (ESI⁺): m/z calcd for C₂₉H₃₈NaO₇Si: 549.2285 [M⁺+Na];

found: 549.2288; elemental analysis calcd (%) for C₂₉H₃₈O₇Si (526.69): C

66.13, H 7.27; found: C 66.11, H 7.58.

4,8-Anhydro-9-O-(tert-butyldiphenylsilyl)-1,5-dideoxy-6,7-di-O-methyl-d-

manno-nono-2,3-diulose (38): Prepared from 32 (70 mg, 0.155 mmol) fol-

lowing the general procedure (Method B) using NaIO₄(132 mg,

0.62 mmol) and RuO₂·xH₂O (1.1 mg). The reaction mixture was stirred

at room temperature in the dark for 1 h. The residue was purified by

rapid silica gel column chromatography (hexanes/EtOAc 1:1) to give 38

(47 mg, 0.097 mmol, 63%) as a yellow oil: [a]_D= +13 cm³g^ꢁ1dm^ꢁ1(c=

0.94 in CHCl₃); ¹H NMR (500 MHz, C₆D₆): d=1.18 (s, 9H), 1.60 (ddd,

J=13.9, 9.8, 6.0 Hz, 1H), 1.86 (s, 3H), 2.22 (ddd, J=13.9, 4.4, 3.8 Hz,

1H), 3.11 (s, 3H), 3.23 (dd, J=7.9, 7.9 Hz, 1H), 3.35 (s, 3H), 3.41 (ddd,

J=9.8, 7.6, 4.4 Hz, 1H), 3.77 (ddd, J=7.9, 4.4, 2.8 Hz, 1H), 3.98 (dd, J=

11.0, 4.4 Hz, 1H), 4.02 (dd, J=11.0, 2.8 Hz, 1H), 4.89 (dd, J=6.0, 3.8 Hz,

1H), 7.21–7.86 ppm (m, 10H); ¹³C NMR (125.7 MHz, C₆D₆): d=19.5 (C),

24.4 (CH₃), 27.0 (3ꢆCH₃), 28.6 (CH₂), 56.6 (CH₃), 59.7 (CH₃), 63.6

(CH₂), 72.5 (CH), 77.6 (CH), 78.6 (CH), 79.0 (CH), 127.8–136.2 (10ꢆ

4,8-Anhydro-1,6-dideoxy-5,7,9-tri-O-methyl-d-altro-nono-2,3-diulose

(39): Prepared from 33 (111 mg, 0.486 mmol) following the general pro-

cedure (Method A) using dimethyl sulfide (71 mL, 0.970 mmol). The mix-

ture was stirred at room temperature in the dark for 6 h and concentrat-

ed under reduced pressure. The residue was purified by rapid silica gel

column chromatography (hexanes/EtOAc 7:3!6:4) to give 39 (83 mg,

0.315 mmol, 65%) as a yellow oil: [a]_D= +126 cm³g^ꢁ1dm^ꢁ1(c=1.3 in

CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=1.72 (ddd, J=13.2, 8.8, 7.6 Hz,

1H), 2.19 (ddd, J=13.2, 5.1, 3.8 Hz, 1H), 2.26 (s, 3H), 3.27 (s, 3H), 3.35

(s, 3H), 3.36 (m, 1H), 3.40 (s, 3H), 3.55 (dd, J=10.7, 4.7 Hz, 1H), 3.64

(dd, J=10.7, 2.2 Hz, 1H), 3.87 (ddd, J=10.7, 6.6, 3.8 Hz, 1H), 4.10 (ddd,

J=9.2, 4.7, 2.2 Hz, 1H), 5.38 ppm (d, J=6.9 Hz, 1H); ¹³C NMR

(100.6 MHz, CDCl₃): d=23.4 (CH₃), 28.7 (CH₂), 56.8 (CH₃), 56.9 (CH₃),

Chem. Eur. J. 2013, 00, 0 – 0

ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

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E. I. Leon, E. Suꢄrez et al.

59.2 (CH₃), 72.1 (CH₂), 73.4 (CH), 74.1 (CH), 74.7 (CH), 75.7 (CH),

197.7 (C), 199.4 ppm (C); IR (film): n˜ =2933, 1716 cm^ꢁ1; MS (EI): m/z

(%): 260 (<1) [M⁺]; HRMS (EI): m/z: calcd for: 260.1260 [M⁺]; found:

260.1261; elemental analysis calcd (%) for C₁₂H₂₀O₆(260.28): C 55.37, H

7.74; found: C 55.52, H 7.73.

and irradiated with a daylight lamp at 15–208C. The reaction was moni-

tored by ¹H NMR spectroscopy, complete consumption of starting mate-

rial 5 was observed after 12 h, leading to exclusive formation of photoen-

ol 50. The solution could be concentrated at low temperature under re-

duced pressure but 50 was not stable enough to withstand chromato-

graphic purification (silica gel or alumina). Notwithstanding, the crude

residue (colorless oil) was pure enough to allow the complete analytical

and spectroscopic characterization. [a]_D= +32.3 cm³g^ꢁ1dm^ꢁ1(c=1.28 in

CHCl₃); ¹H NMR (500 MHz, CDCl₃, 208C): d=0.94 (s, 9H), 0.95 (s,

9H), 1.63 (ddd, J=14.3, 6.6, 2.8 Hz, 1H), 2.10 (ddd, J=14.4, 10.6, 2.2 Hz,

1H), 2.24 (s, 3H), 3.03 (s, 3H), 4.20 (d, J=17.7 Hz, 1H), 4.38 (dd, J=6.3,

2.2 Hz, 1H), 4.52 (ddd, J=10.8, 8.0, 2.7 Hz, 1H), 4.53 (d, J=17.9 Hz,

1H), 5.34 (dd, J=8.2, 1.3 Hz, 1H), 6.49 (d, J=1.3 Hz, 1H), 7.16–7.34 (m,

10H), 7.43–7.57 ppm (m, 10H); ¹³C NMR (125.7 MHz, CDCl₃, 208C): d=

19.18 (C), 19.21 (C), 23.1 (CH₃), 26.7 (3ꢆCH₃), 26.9 (3ꢆCH₃), 34.5

(CH₂), 56.7 (CH₃), 68.3 (CH₂), 71.1 (CH), 74.6 (CH), 115.6 (CH), 127.6

(2ꢆCH), 127.68 (4ꢆCH), 127.71 (2ꢆCH), 129.67 (CH), 129.69 (CH),

129.86 (CH), 129.88 (CH), 133.6 (C), 133.8 (C), 133.06 (C), 134.12 (C),

135.5 (4ꢆCH), 135.7 (2ꢆCH), 135.8 (2ꢆCH), 148.4 (C), 194.9 (C),

208.6 ppm (C); IR (CHCl₃, 0.2 mm): n˜ =3441, 2246, 1733, 1684,

1661 cm^ꢁ1; UV/Vis (CH₂Cl₂): l_max(e)=271 (sh) (3055), 264 (3841), 261

(3877), 255 (sh) (3441), 227 (5628 mol^ꢁ1m³cm^ꢁ1); MS (EI): m/z (%): 665

(<1) [M⁺ꢁAc], 651 (4), 135 (100); HRMS (ESI⁺): m/z calcd for

C₄₂H₅₂NaO₆Si₂: 731.3200 [M⁺+Na]; found: 731.3198; elemental analysis

calcd (%) for C₄₂H₅₂O₆Si₂(709.03): C 71.15, H 7.39; found: C 71.02, H

7.40.

Photocyclization of 39: Method A: A deoxygenated solution of diketone

39 (41 mg, 0.156 mmol) in dry C₆D₆(0.6 mL), was placed in a resonance

tube and irradiated with a daylight lamp at 308C for 3 h. The reaction

1

was monitored by H NMR spectroscopy, complete transformation into a

mixture of the enol intermediate and the cyclized product 46 was ob-

served. The mixture was heated at 458C in the dark for 1 h, concentrated

under reduced pressure and the residue purified by Chromatotron chro-

matography (Al₂O₃, hexanes/EtOAc 9:1!7:3) to give 46 (23 mg,

0.089 mmol, 57%) as a colorless oil.

Method B: A deoxygenated solution of diketone 39 (34 mg, 0.131 mmol)

in dry C₆D₆(0.6 mL), was placed in a resonance tube and irradiated with

1

a daylight lamp at 458C for 7 h. The reaction was monitored by H NMR

spectroscopy, complete transformation into the cyclized product 46 was

observed. The mixture was concentrated under reduced pressure and the

residue purified by Chromatotron chromatography (Al₂O₃, hexanes/

EtOAc 9:1!7:3 as eluents) to give (2S,3aS,4R,6S,6aR)-2-hydroxy-4,6-di-

methoxy-6a-(methoxymethyl)-2-methyltetrahydro-2H-cyclopenta[b]fur-

an-3ACHTUNGTRENNUNG(3aH)-one (46) (20 mg, 0.077 mmol, 59%) as a colorless oil. [a]_D=

+139 cm³g^ꢁ1dm^ꢁ1(c=1.01 in CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=

1.35 (d, J=0.95 Hz, 3H, OH coupling), 1.95 (ddd, J=14.8, 6.0, 5.4 Hz,

1H), 2.13 (dddd, J=14.5, 3.2, 3.2, 1.3 Hz, 1H), 3.13 (dd, J=1.3, 1.3 Hz,

1H), 3.35 (s, 3H), 3.37 (s, 3H), 3.48 (s, 3H), 3.75 (d, J=10.1 Hz, 1H),

3.76 (dd, J=5.0, 3.4 Hz, 1H), 3.78 (d, J=10.4 Hz, 1H), 3.79 (ddd, J=5.7,

2.5, 2.5 Hz, 1H), 5.35 ppm (d, J=0.9 Hz, 1H, OH); ¹H NMR (500 MHz,

C₆D₆): d=1.60 (s, 3H), 1.72 (ddd, J=14.2, 5.7, 5.7 Hz, 1H), 1.89 (ddd,

J=14.2, 4.7, 4.7 Hz, 1H), 2.70 (s, 3H), 2.98 (s, 3H), 3.13 (s, 3H), 3.18 (d,

J=2.8 Hz, 1H), 3.507 (dd, J=5.0, 5.0 Hz, 1H), 3.513 (d, J=10.4 Hz, 1H),

3.54 (d, J=10.4 Hz, 1H), 3.66 (ddd, J=6.3, 3.8, 2.8 Hz, 1H), 5.47 ppm

(br s, 1H); ¹³C NMR (100.6 MHz, CDCl₃): d=21.1 (CH₃), 35.4 (CH₂),

55.8 (CH), 57.3 (CH₃), 57.8 (CH₃), 59.5 (CH₃), 73.9 (CH₂), 84.5 (CH),

87.5 (CH), 91.2 (C), 98.7 (C), 210.1 ppm (C); ¹³C NMR (125.7 MHz,

C₆D₆): d=21.6 (CH₃), 35.8 (CH₂), 55.6 (CH), 56.8 (CH₃), 57.1 (CH₃),

58.7 (CH₃), 74.3 (CH₂), 83.4 (CH), 87.6 (CH), 91.6 (C), 99.6 (C),

209.6 ppm (C); IR (film): n˜ =3348, 2936, 1760 cm^ꢁ1; MS (ESI⁺): m/z

(%): 283 (100) [M⁺+Na]; HRMS (ESI⁺): m/z calcd for C₁₂H₂₀NaO₆:

283.1158 [M⁺+Na]; found: 283.1147; elemental analysis calcd (%) for

C₁₂H₂₀O₆(260.28): C 55.37, H 7.74; found: C 55.38, H 7.74.

Kinetic studies: The unlabeled photoenol 50 (9.4 mg, 0.013 mmol) was

dissolved in [D₆]benzene (0.6 mL), transferred to an NMR tube and im-

mediately placed into the preheated probe (408C) of a 500 MHz NMR

spectrometer to minimize spontaneous cyclization of 50. The integral of

vinyl proton at 5.10 ppm (1H, dd, J=8.2, 1.3 Hz) were monitored over

14 h and data were collected every 30 min. The same procedure was car-

ried out for the deuterated photoenol [D₁]50 (11.5 mg, 0.016 mmol) dis-

solved in [D₆]benzene (0.6 mL), prepared by hydroxyl proton exchange

with D₂O. The vinyl proton now appears at 5.11 ppm (1H, d, J=8.2 Hz).

Since [D₁]50 was not isotopically pure (contained 11% of unlabeled 50)

the appropriate corrections were introduced during the concentration cal-

culations. The kinetic isotope effect (KIE) value (k_H/k_D=3.7) was com-

puted by plotting the selected concentration data against time and fitting

the data to a first-order simulation to obtain the rate constants for the

cyclization of both 50 (k_H=5.42ꢆ10^ꢁ5, R²=0.999) and [D₁]50 (k_D=1.48ꢆ

10^ꢁ5, R²=0.999).

4,8-Anhydro-7,9-bis-O-(tert-butyldiphenylsilyl)-1,6-dideoxy-5-O-methyl-

d-altro-nono-2,3-diulose (40): Prepared from 34 (101 mg, 0.15 mmol) fol-

lowing the general procedure (Method A) using dimethyl sulfide (22 mL,

0.3 mmol). The mixture was stirred at room temperature in the dark for

5 h and concentrated under reduced pressure. The residue was purified

by rapid silica gel column chromatography (hexanes/EtOAc 95:5!9:1)

Photocyclization of 40: A deoxygenated solution of diketone 40 (19 mg,

0.027 mmol) in dry C₆D₆(0.6 mL), was placed in a resonance tube and ir-

radiated with a daylight lamp at 258C for 7 h. The reaction was moni-

tored by ¹H NMR spectroscopy, complete transformation into the enol

intermediate 50 was observed. The enol was heated at 408C in the dark

for 8 h, leading to exclusive formation of carbocycle 47. The solution was

concentrated under reduced pressure and the residue purified by Chro-

matotron chromatography on alumina (hexanes/EtOAc 9:1) to give

(2S,3aS,4R,6S,6aR)-4-(benzyloxy)-6-[(tert-butyldiphenylsilyl)oxy]-6a-

[(tert-butyldiphenylsilyl)oxy]methyl-2-hydroxy-2-methyltetrahydro-2H-cy-

to give 40 (81.4 mg, 0.11 mmol, 77%) as

a yellow oil: [a]_D= +

57.9 cm³g^ꢁ1dm^ꢁ1(c=0.95 in CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=

0.98 (s, 9H), 1.01 (s, 9H), 1.56 (ddd, J=12.6, 9.3, 9.0 Hz, 1H), 1.91 (ddd,

J=12.5, 4.7, 4.7 Hz, 1H), 2.25 (s, 3H), 3.10 (s, 3H), 3.44 (ddd, J=10.4,

6.9, 4.6 Hz, 1H), 3.75 (dd, J=11.2, 4.9 Hz, 1H), 3.82 (ddd, J=10.1, 9.8,

4.5 Hz, 1H), 3.96 (dd, J=11.4, 2.2 Hz, 1H), 4.21 (ddd, J=10.7, 4.9,

2.9 Hz, 1H), 5.30 (d, J=6.7 Hz, 1H), 7.27–7.42 (m, 12H), 7.61–7.64 ppm

(m, 8H); ¹³C NMR (125.7 MHz, CDCl₃): d=19.2 (C), 19.3 (C), 23.5

(CH₃), 26.8 (6ꢆCH₃), 34.0 (CH₂), 56.9 (CH₃), 63.9 (CH₂), 66.3 (CH), 72.9

(CH), 75.8 (CH), 78.0 (CH), 127.5 (4ꢆCH), 127.6 (2ꢆCH), 127.7 (2ꢆ

CH), 129.42 (CH), 129.44 (CH), 129.7 (CH), 129.8 (CH), 133.3 (C), 133.6

(C), 133.9 (C), 134.1 (C), 135.7 (2ꢆCH), 135.76 (2ꢆCH), 135.78 (2ꢆ

CH), 135.82 (2ꢆCH), 197.9 (C), 200.3 ppm (C); IR (CHCl₃, 0.2 mm): n˜ =

2933, 1714 cm^ꢁ1; MS (EI): m/z (%): 708 (<1) [M⁺], 651 (18), 135 (100);

HRMS (EI): m/z calcd for C₄₂H₅₂O₆Si₂: 708.3302 [M⁺]; found: 708.3286;

elemental analysis calcd (%) for C₄₂H₅₂O₆Si₂(709.03): C 71.15, H 7.39;

found: C 71.48, H 7.00.

clopenta[b]furan-3ACTHNUTRGNE(NUG 3aH)-one (47) (14.8 mg, 0.021 mmol, 78%) as a crys-

talline solid: M.p. 105.7–107.98C (MeOH); [a]_D= +30.3 cm³g^ꢁ1dm^ꢁ1(c=

1.56 in CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=0.82 (s, 9H), 1.08 (s,

9H), 1.36 (s, 3H), 1.65 (dddd, J=13.9, 4.6, 4.6, 0.7 Hz, 1H), 1.76 (ddd,

J=14.2, 5.7, 5.7 Hz, 1H), 3.18 (dd, J=2.6, 0.7 Hz, 1H), 3.26 (s, 3H), 3.63

(ddd, J=5.9, 4.7, 2.9 Hz, 1H), 4.00 (d, J=11.7 Hz, 1H), 4.05 (d, J=

11.7 Hz, 1H), 4.14 (dd, J=5.4, 5.1 Hz, 1H), 5.38 (s, 1H), 7.24–7.29 (m,

4H), 7.35–7.51 (m, 12H), 7.64–7.67 ppm (m, 4H); ¹³C NMR (100.6 MHz,

CDCl₃): d=19.1 (C), 19.2 (C), 20.7 (CH₃), 26.7 (3ꢆCH₃), 26.9 (3ꢆCH₃),

40.0 (CH₂), 54.8 (CH), 56.8 (CH₃), 66.8 (CH₂), 79.6 (CH), 82.2 (CH), 93.3

(C), 99.0 (C), 127.5 (2ꢆCH), 127.6 (2ꢆCH), 128.0 (2ꢆCH), 128.1 (2ꢆ

CH), 129.8 (2ꢆCH), 130.1 (CH), 130.3 (CH), 131.4 (C), 131.5 (C), 132.8

(C), 133.5 (C), 135.6 (2ꢆCH), 135.76 (2ꢆCH), 135.81 (2ꢆCH), 135.89

ꢀ

G

(2ꢆCH), 209.9 ppm (C); IR (CHCl₃, 0.2 mm): n=3672, 3357, 2932,

1763 cm^ꢁ1; MS (EI): m/z (%): 651 (1) [M⁺ꢁtBu], 633 (4), 135 (100);

HRMS (ESI⁺): m/z calcd for C₄₂H₅₂NaO₆Si₂: 731.3200 [M⁺+Na]; found:

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www.chemeurj.org

ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 0000, 00, 0 – 0

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Synthesis of Polyhydroxylated Cyclopentitols

FULL PAPER

731.3213; elemental analysis calcd (%) for C₄₂H₅₂O₆Si₂(709.03): C 71.15,

H 7.39; found: C 71.21, H 7.40.

4,8-Anhydro-9-(tert-butyldiphenylsilyl)-1,6,7-trideoxy-5-O-methyl-d-ara-

bino-nono-2,3-diulose (42): Prepared from 36 (36.7 mg, 0.09 mmol) fol-

lowing the general procedure (Method B) using NaIO₄(56 mg,

0.26 mmol) and RuO₂·xH₂O (0.25 mg). The reaction mixture was stirred

at room temperature in the dark for 30 min. The residue was purified by

rapid silica gel column chromatography (EtOAc) to give 42 (28.1 mg,

0.06 mmol, 71%) as a yellow oil: [a]_D= +46 cm³g^ꢁ1dm^ꢁ1(c=1.53 in

4,8-Anhydro-6,7-dideoxy-5,9-di-O-methyl-d-arabino-nono-2,3-diulose

(41): Prepared from 35 (25.3 mg, 0.13 mmol) following the general proce-

dure (Method A) using dimethyl sulfide (40 mL, 0.54 mmol). The mixture

was stirred at room temperature in the dark for 2 h and concentrated

under reduced pressure. The residue was purified by rapid silica gel

column chromatography (hexanes/EtOAc 8:2) to give 41 (20.4 mg,

0.09 mmol, 69%) as a yellow oil. [a]_D= +116 cm³g^ꢁ1dm^ꢁ1(c=2.57 in

CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=1.48 (m, 1H), 1.65 (m, 1H),

1.75 (m, 1H), 1.97 (m, 1H), 2.27 (s, 3H), 3.27 (s, 3H), 3.38 (s, 3H), 3.39–

3.43 (m, 2H), 3.74 (ddd, J=9.2, 6.3, 4.0 Hz, 1H), 4.44 (m, 1H), 5.43 ppm

(d, J=6.3 Hz, 1H); ¹³C NMR (125.7 MHz, CDCl₃): d=23.50 (CH₂), 23.54

(CH₂), 24.1 (CH₂), 56.9 (CH₃), 59.2 (CH₃), 70.6 (CH), 74.1 (CH), 75.0

(CH₂), 76.3 (CH), 197.8 (C), 200.8 ppm (C); IR (CHCl₃, 0.2 mm): n˜ =

2934, 1771, 1714, 1099 cm^ꢁ1; MS (ESI⁺): m/z (%): 253 (100) [M⁺+Na],

229 (3); HRMS (ESI⁺): m/z calcd for C₁₁H₁₈NaO₅: 253.1052 [M⁺+Na];

found: 253.1042; elemental analysis calcd (%) for C₁₁H₁₈O₅(230.26): C

57.38, H 7.88; found: C 57.30, H 7.85.

1

CHCl₃); H NMR (500 MHz, CDCl₃): d=1.06 (s, 9H), 1.51 (m, 1H), 1.66

(m, 1H), 1.88 (m, 1H), 1.96 (m, 1H), 2.29 (s, 3H), 3.27 (s, 3H), 3.66 (dd,

J=10.5, 5.7 Hz, 1H), 3.72 (ddd, J=5.8, 4.7, 4.1 Hz, 1H), 3.74 (dd, J=

10.5, 4.9 Hz, 1H), 4.33 (m, 1H), 5.32 (d, J=5.8 Hz, 1H), 7.40 (m, 6H),

7.67 ppm (m, 4H); ¹³C NMR (125.7 MHz, CDCl₃): d=19.2 (C), 23.2

(CH₂), 23.6 (CH₂), 23.7 (CH₃), 26.8 (3ꢆCH₃), 56.8 (CH₃), 65.8 (CH₂),

72.5 (CH), 74.0 (CH), 76.2 (CH), 127.6 (4ꢆCH), 129.6 (2ꢆCH), 133.46

(C), 133.49 (C), 135.6 (4ꢆCH), 198.1 (C), 200.6 ppm (C); IR (CHCl₃,

0.2 mm): n˜ =2936, 1714 cm^ꢁ1; MS (EI): m/z (%): 397 (58) [M⁺ꢁtBu], 199

(75); HRMS (EI): m/z calcd for C₂₂H₂₅O₅Si: 397.1471 [M⁺ꢁtBu]; found:

397.1466; elemental analysis calcd (%) for C₂₆H₃₄O₅Si (454.63): C 68.69,

H 7.54; found: C 68.61, H 7.60.

AHCTUNGTERG(NNUN 3Z,5R)-9-[(tert-Butyldiphenylsilyl)oxy]-3-hydroxy-5-methoxy-3-nonene-

ACHTUNGTRENNUNG(3E,5R)-3-Hydroxy-5,9-dimethoxy-3-nonene-2,8-dione (51): A deoxygen-

2,8-dione (52): A solution of 42 (49.7 mg, 0.11 mmol) in purified CDCl₃

(0.3 mL), was placed in a resonance tube and irradiated with a daylight-

lamp at 30–358C for 3 h. The reaction was monitored by using ¹H NMR

spectroscopy to give the photoenol 52 (47.3 mg, 0.1 mmol, 96%) as a yel-

lowish oil that could not withstand chromatographic purification (silica

gel or alumina). Nevertheless, the crude residue was pure enough to

allow the complete analytical and spectroscopic characterization. [a]_D=

+4 cm³g^ꢁ1dm^ꢁ1(c=0.47 in CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=

1.10 (s, 9H), 1.84 (m, 1H), 1.96 (m, 1H), 2.36 (s, 3H), 2.58 (ddd, J=17.8,

8.2, 6.3 Hz, 1H), 2.67 (ddd, J=17.8, 8.5, 6.3 Hz, 1H), 3.29 (s, 3H), 4.19 (s,

2H), 4.26 (ddd, J=8.2, 7.3, 6.0 Hz, 1H), 5.47 (dd, J=8.2, 1.1 Hz, 1H),

6.60 (d, J=1.1 Hz, 1H), 7.37–7.44 (m, 6H), 7.64–7.67 ppm (m, 4H);

¹³C NMR (125.7 MHz, CDCl₃): d=19.2 (C), 23.1 (CH₃), 26.7 (3ꢆCH₃),

28.0 (CH₂), 34.3 (CH₂), 56.9 (CH₃), 69.7 (CH₂), 75.1 (CH), 115.5 (CH),

127.8 (4ꢆCH), 129.9 (2ꢆCH), 132.7 (2ꢆC), 135.5 (4ꢆCH), 148.7 (C),

194.8 (C), 209.6 ppm (C); IR (CHCl₃, 0.2 mm): n˜ =3435, 2933, 2249,

1714, 1681, 1662 cm^ꢁ1; UV/Vis (CH₂Cl₂): l_max(e)=272 (sh) (2914), 264

(3841), 261 (3877), 255 (sh) (3441), 227 nm (5628 mol^ꢁ1m³cm^ꢁ1); MS

(EI): m/z (%): 437 (5) [M⁺ꢁOH], 365 (38), 199 (100); HRMS (EI): m/z

calcd for C₂₆H₃₃O₄Si: 437.2148 [M⁺ꢁOH]; found: 437.2140; elemental

analysis calcd (%) for C₂₆H₃₄O₅Si (454.63): C 68.69, H 7.54; found: C

68.83, H 7.30.

ated solution of diketone 41 (37.0 mg, 0.16 mmol) in purified CDCl₃

(0.3 mL), was placed in a resonance tube and irradiated with a daylight

1

lamp at 30–338C. The reaction was monitored by H NMR spectroscopy;

complete consumption of starting material was observed after 4.5 h, lead-

ing to exclusive formation of intermediate photoenol 51. The solution

could be concentrated at low temperature under reduced pressure but 51

was not stable enough to withstand chromatographic purification (silica

gel or alumina). Notwithstanding, the crude residue (32.5 mg, 0.14 mmol,

88%) was pure enough to allow the complete analytical and spectroscop-

ic characterization.

Compound 51: colorless oil. [a]_D= +19 cm³g^ꢁ1dm^ꢁ1(c=0.32 in CHCl₃);

¹H NMR (500 MHz, CDCl₃): d=1.89 (m, 1H), 1.96 (m, 1H), 2.38 (s,

3H), 2.50 (ddd, J=17.4, 8.2, 6.1 Hz, 1H), 2.59 (ddd, J=17.4, 8.2, 6.6 Hz,

1H), 3.30 (s, 3H), 3.41 (s, 3H), 4.01 (s, 2H), 4.27 (ddd, J=8.3, 7.4,

5.6 Hz, 1H), 5.48 (dd, J=8.3, 1.2 Hz, 1H), 6.61 ppm (d, J=1.2 Hz, 1H);

¹³C NMR (125.7 MHz, CDCl₃): d=23.1 (CH₃), 28.2 (CH₂), 34.6 (CH₂),

56.9 (CH₃), 59.3 (CH₃), 75.1 (CH), 77.6 (CH₂), 115.5 (CH), 148.8 (C),

194.8 (C), 208.1 ppm (C); IR (CHCl₃, 0.2 mm): n˜ =3435, 2935, 2252,

1731, 1682, 1663, 1350 cm^ꢁ1

; UV/Vis (CH₂Cl₂): l_max(e)=260 nm

(8003 mol^ꢁ1m³cm^ꢁ1); MS (EI): m/z (%): 230 (1) [M⁺], 213 (1), 199 (1),

198 (12); HRMS (EI): m/z: calcd for C₁₁H₁₈O₅: 230.1154 [M⁺]; found:

230.1153; elemental analysis calcd (%) for C₁₁H₁₈O₅(230.26): C 57.38, H

7.88; found: C 57.58, H 7.91.

Photocyclization of 42:

A deoxygenated solution of diketone 42

(58.7 mg, 0.127 mmol) in dry C₆D₆(0.3 mL), was irradiated with a day-

light lamp at 36–408C for 5 h. The reaction was monitored by ¹H NMR

spectroscopy, complete transformation into the enol intermediate 52 was

observed. The enol was heated at 608C in the dark for 2 h, concentrated

under reduced pressure and the residue purified by column chromatogra-

phy (Al₂O₃, hexanes/EtOAc 95:5) to give an inseparable mixture of hem-

iketal diastereomers (35.9 mg, 0.078 mmol, d.r. 10:1, 61%) (major

Photocyclization of 41: A deoxygenated solution of diketone 41 (51.2 mg,

0.23 mmol) in dry C₆D₆(0.4 mL), was placed in a resonance tube and ir-

radiated with a daylight lamp at 308C for 4.5 h. The reaction was moni-

tored by ¹H NMR spectroscopy, complete transformation into the inter-

mediate photoenol 51 was observed. The mixture was heated at 608C in

the dark for 7 h, concentrated under reduced pressure and the residue

purified by Chromatotron chromatography (Al₂O₃, hexanes/EtOAc 8:2)

to give (2S,3aS,4R,6aR)-2-hydroxy-4-methoxy-6a-(methoxymethyl)-2-

isomer:

(2S,3aS,4R,6aR)-6a-[(tert-butyldiphenylsilyl)oxy]methyl-2-hy-

(3aH)-one

droxy-4-methoxy-2-methyltetrahydro-2H-cyclopenta[b]furan-3AHCTNUGTRENNNUG

methyltetrahydro-2H-cyclopenta[b]furan-3

A

(48)

(26.8 mg,

(49)) as a colorless oil: [a]_D= +62 cm³g^ꢁ1dm^ꢁ1(c=0.98 in CHCl₃);

¹H NMR (500 MHz, CDCl₃): d (major isomer) =1.07 (s, 9H), 1.45 (s,

3H), 1.52 (dddd, J=12.9, 12.9, 6.9, 4.1 Hz, 1H), 1.68 (ddd, J=12.9, 12.9,

6.6 Hz, 1H), 1.78 (ddd, J=13.2, 6.9, 0.0 Hz, 1H), 1.86 (dddd, J=13.5, 6.4,

1.3, 1.3 Hz, 1H), 3.10 (d, J=1.9 Hz, 1H), 3.22 (s, 3H), 3.48 (d, J=

11.0 Hz, 1H), 3.86 (br d, J=4.1 Hz, 1H), 3.99 (d, J=11.0 Hz, 1H), 5.35

(d, J=0.9 Hz, 1H), 7.38–7.49 (m, 6H), 7.66–7.69 ppm (m, 4H); ¹³C NMR

(100.6 MHz, CDCl₃;): d (major isomer)=19.1 (C), 20.3 (CH₃), 26.8 (3ꢆ

CH₃), 30.3 (CH₂), 33.9 (CH₂), 55.5 (CH), 56.2 (CH₃), 69.0 (CH₂), 85.5

(CH), 91.6 (C), 98.8 (C), 128.0 (2ꢆCH), 128.1 (2ꢆCH), 130.2 (CH),

130.4 (CH), 131.41 (C), 131.45 (C), 135.6 (2ꢆCH), 135.7 (2ꢆCH),

0.12 mmol, 52%) as a colorless oil: [a]_D= +101 cm³g^ꢁ1dm^ꢁ1(c=0.34 in

CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=1.37 (brd, J=1.4 Hz, 3H), 1.52

(dddd, J=13.5, 12.2, 8.0, 4.5 Hz, 1H), 1.87 (m, 2H), 1.94 (dddd, J=13.5,

5.8, 1.6, 1.6 Hz, 1H), 3.05 (d, J=1.9 Hz, 1H), 3.32 (s, 3H), 3.38 (d, J=

9.8 Hz, 1H), 3.48 (s, 3H), 3.74 (d, J=9.8 Hz, 1H), 3.86 ppm (d, J=

4.2 Hz, 1H); ¹H NMR (500 MHz, C₆D₆): d=1.26–1.35 (m, 1H), 1.61 (d,

J=0.95 Hz, 3H), 1.58–1.69 (m, 3H), 2.68 (s, 3H), 2.83 (d, J=9.8 Hz,

1H), 2.94 (s, 3H), 3.04 (br s, 1H), 3.24 (d, J=9.5 Hz, 1H), 3.80 (d, J=

4.1 Hz, 1H), 5.40 ppm (d, J=1.3 Hz, 1H, OH); ¹³C NMR (100.6 MHz,

CDCl₃): d=20.4 (CH₃), 29.9 (CH₂), 33.9 (CH₂), 55.4 (CH), 56.4 (CH₃),

59.2 (CH₃), 77.1 (CH₂), 85.7 (CH), 90.1 (C), 98.8 (C), 209.5 ppm (C); IR

(CHCl₃, 0.2 mm): n˜ =3364, 2936, 1762, 1094 cm^ꢁ1; MS (ESI⁺): m/z (%):

285 (28) [M⁺+MeOH+Na], 253 (100) [M⁺+Na]; HRMS (ESI⁺): m/z

calcd for C₁₁H₁₈NaO₅: 253.1052 [M⁺+Na]; found: 253.1047; elemental

analysis calcd (%) for C₁₁H₁₈O₅(230.25): C 57.38, H 7.88; found: C 57.43,

H 7.87.

209.3 ppm (C); IR (CHCl₃, 0.2 mm): n˜ =3356, 2935, 1762 cm^ꢁ1

; MS

(ESI⁺): m/z (%): 477 (100) [M⁺+Na]; HRMS (ESI⁺): m/z calcd for

C₂₆H₃₄NaO₅Si: 477.2073 [M⁺+Na]; found: 477.2076; elemental analysis

calcd (%) for C₂₆H₃₄O₅Si (454.63): C 68.69, H 7.54; found: C 68.64, H

7.76.

Chem. Eur. J. 2013, 00, 0 – 0

ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

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E. I. Leon, E. Suꢄrez et al.

4,8-Anhydro-9-O-(3,5-dinitrobenzoyl)-1,6,7-trideoxy-5-O-methyl-d-arabi-

no-nono-2,3-diulose (43): Prepared from 37 (65.5 mg, 0.17 mmol) follow-

ing the general procedure (Method B) using NaIO₄(111.1 mg,

0.52 mmol) and RuO₂·xH₂O (0.5 mg). The reaction mixture was stirred

at room temperature in the dark for 30 min. The residue was purified by

rapid silica gel column chromatography (EtOAc) to give 43 (28.1 mg,

0.06 mmol, 71%) as a yellow oil. [a]_D= +47 cm³g^ꢁ1dm^ꢁ1(c=0.59 in

CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=1.52 (m, 1H), 1.79–1.88 (m,

2H), 1.94 (m, 1H), 2.28 (s, 3H), 3.28 (s, 3H), 3.88 (ddd, J=7.6, 6.4,

3.6 Hz, 1H), 4.41 (dd, J=11.7, 3.3 Hz, 1H), 4.48 (dd, J=11.7, 7.5 Hz,

1H), 4.61 (m, 1H), 5.38 (d, J=6.4 Hz, 1H), 9.22 ppm (m, 3H); ¹³C NMR

(125.7 MHz, CDCl₃): d=22.2 (CH₂), 23.1 (CH₂), 23.5 (CH₃), 56.9 (CH₃),

67.9 (CH₂), 69.4 (CH), 75.0 (CH), 75.8 (CH), 122.4 (CH), 129.6 (2ꢆCH),

133.8 (C), 148.7 (2ꢆC), 162.5 (C), 197.6 (C), 199.2 ppm (C); IR (CHCl₃,

0.2 mm): n˜ =2945, 1732 cm^ꢁ1; MS (EI): m/z (%): 410 (3) [M⁺], 378 (4),

340 (14), 339 (85); HRMS (EI): m/z calcd for C₁₇H₁₈N₂O₁₀: 410.0961 [M⁺

]; found: 410.0957; elemental analysis calcd (%) for C₁₇H₁₈N₂O₁₀

(410.33): C 49.76, H 4.42, N 6.83; found: C 49.68, H 4.37, N 6.61.

mixture was concentrated under reduced pressure and the residue puri-

fied by silica gel column chromatography (hexanes/EtOAc 7:3) to give

(2S,3aR,4R,5R,6S,6aS)-6a-[(tert-butyldiphenylsilyl)oxy]methyl-4,5,6-trime-

thoxy-2-methyl-3-oxohexahydro-2H-cyclopenta[b]furan-2-yl acetate (62)

(13 mg, 0.023 mmol, 30%) as a colorless oil. The sensitive photoenol in-

termediate was detected by NMR spectroscopy but in this case could not

be obtained in pure state. Only clearly distinguished signals from the re-

1

action mixture are reported: H NMR (400 MHz, C₆D₆): d=1.26 (s, 9H),

1.77 (s, 3H), 2.90 (s, 3H), 3.10 (s, 3H), 3.6 (s, 3H), 4.71 (d, J=18.3 Hz,

1H), 4.85 (d, J=18.5 Hz, 1H), 5.33 (brd, J=9.3 Hz, 1H), 6.73 ppm (brs,

1H, OH).

Compound 62: [a]_D=ꢁ4 cm³g^ꢁ1dm^ꢁ1(c=1.00 in CHCl₃); ¹H NMR

(500 MHz, CDCl₃): d=1.07 (s, 9H), 1.52 (s, 3H), 1.85 (s, 3H), 3.41 (d,

J=1.9 Hz, 1H), 3.431 (dd, J=7.9, 4.7 Hz, 1H), 3.434 (s, 3H), 3.46 (s,

3H), 3.52 (s, 3H), 3.72 (d, J=10.4 Hz, 1H), 3.79 (dd, J=4.7, 2.1 Hz, 1H),

3.87 (d, J=10.1 Hz, 1H), 4.19 (d, J=8.2 Hz, 1H), 7.35–7.70 ppm (m,

10H); ¹³C NMR (125.7 MHz, CDCl₃): d=19.3 (C), 20.4 (CH₃), 22.4

(CH₃), 26.8 (3ꢆCH₃), 51.8 (CH), 57.5 (CH₃), 58.0 (CH₃), 60.1 (CH₃), 64.8

(CH₂), 79.5 (CH), 82.4 (CH), 85.6 (CH), 88.3 (C), 101.1 (C), 127.6–135.7

(10ꢆCH), 132.9 (C), 133.0 (C), 169.7 (C), 207.7 ppm (C); IR (film): n˜ =

2921, 1763, 1743 cm^ꢁ1; MS (ESI⁺): m/z (%): 579 (100) [M⁺+Na]; HRMS

(ESI⁺): m/z calcd for C₃₀H₄₀NaO₈Si; 579.2390 [M⁺+Na]; found:

579.2396; elemental analysis calcd (%) for C₃₀H₄₀O₈Si (558.72): C 64.72,

H 7.24; found: C 66.70, H 7.05.

ACHTUNGTRENNUNG(5R,6Z)-7-Hydroxy-5-methoxy-2,8-dioxo-6-nonenyl 3,5-dinitrobenzoate

(53): A deoxygenated solution of diketone 43 (47.6 mg, 0.12 mmol) in pu-

rified CDCl₃(0.3 mL) was placed in a resonance tube and irradiated with

1

a daylight lamp at 308C for 6 h. The reaction was monitored by H NMR

spectroscopy and complete transformation into the photoenol intermedi-

ate was observed. The solution was concentrated at low temperature

under reduced pressure to give 53, which was not stable enough to with-

stand chromatographic purification (silica gel or alumina). Notwithstand-

ing, the crude residue (yellowish oil) was pure enough to allow the com-

4,8-Anhydro-1-deoxy-5,6,7,9-tetra-O-methyl-d-glycero-l-gluco-nono-2,3-

diulose (59): Prepared from 55 (150 mg, 0.581 mmol) following the gener-

al procedure (Method A) using dimethyl sulfide (85 mL, 1.162 mmol).

The mixture was stirred at room temperature in the dark for 3 h and con-

centrated under reduced pressure. The residue was purified by rapid

silica gel column chromatography (hexanes/EtOAc 1:1) to give 59 as a

yellow oil (98 mg, 0.338 mmol, 58%), which was unstable on silica gel.

However, a small analytical sample could be obtained by rapid silica gel

column chromatography (hexanes/EtOAc 7:3). [a]_D=ꢁ30 cm³g^ꢁ1dm^ꢁ1

plete

analytical

and

spectroscopic characterization. [a]_D= +

8 cm³g^ꢁ1dm^ꢁ1(c=1.39, CDCl₃); ¹H NMR (400 MHz, CDCl₃): d=1.94

(m, 1H), 2.03 (m, 1H), 2.39 (s, 3H), 2.61 (m, 2H), 3.32 (s, 3H), 4.30

(ddd, J=8.2, 7.7, 5.6 Hz, 1H), 5.06 (s, 2H), 5.49 (dd, J=8.2, 1.3 Hz, 1H),

6.65 (d, J=1.3 Hz, 1H), 9.20 (d, J=2.1 Hz, 2H), 9.25 ppm (dd, J=2.1,

2.1, 1H); ¹³C NMR (100.6 MHz, CDCl₃): d=23.1 (CH₃), 28.3 (CH₂), 34.7

(CH₂), 57.0 (CH₃), 69.3 (CH₂), 74.9 (CH), 115.1 (CH), 122.7 (CH), 129.7

(2ꢆCH), 133.1 (C), 148.8 (2ꢆC), 148.9 (C), 161.9 (C), 194.7 (C),

201.3 ppm (C); IR (CHCl₃, 0.2 mm): n˜ =3103, 2934, 2258, 1736, 1682,

1

(c=2.14 in CHCl₃); H NMR (400 MHz, CDCl₃): d=2.35 (s, 3H), 3.32 (s,

3H), 3.36 (s, 3H), 3.39–3.56 (m, 3H), 3.44 (s, 3H), 3.51 (s, 3H), 3.83 (dd,

J=4.1, 1.9 Hz, 1H), 4.01 (dd, J=2.2, 1.9 Hz, 1H), 4.19 (dd, J=4.7,

4.4 Hz, 1H), 5.07 ppm (d, J=2.2 Hz, 1H); ¹³C NMR (100.6 MHz,

CDCl₃): d=25.6 (CH₃), 58.3 (CH₃), 58.4 (CH₃), 59.8 (CH₃), 60.0 (CH₃),

73.0 (CH₂), 80.4 (CH), 84.7 (CH), 85.2 (CH), 85.9 (CH), 87.6 (CH), 196.9

(C), 199.7 ppm (C); IR (film): n˜ =2931, 1728, 1714 cm^ꢁ1; MS (EI): m/z

(%): 291 (34) [M⁺+H]; HRMS (EI): m/z calcd for C₁₃H₂₃O₇: 291.1444

[M⁺+H]; found: 291.1414; elemental analysis calcd (%) for C₁₃H₂₂O₇

(290.31): C 53.78, H 7.64; found: C 53.67, H 7.62.

1664 cm^ꢁ1

;

UV/Vis (CH₂Cl₂): l_max(e)=255 (6229), 236 nm

(6110 mol^ꢁ1m³cm^ꢁ1); MS (EI): m/z (%): 410 (<1) [M⁺], 378 (2), 367 (1),

335 (17); HRMS (EI): m/z: calcd for C₁₇H₁₈N₂O₁₀: 410.0961 [M⁺]; found:

410.0967; elemental analysis calcd (%) for C₁₇H₁₈N₂O₁₀(410.33): C 49.76,

H 4.42, N 6.83; found: C 49.91, H 4.45, N 6.45.

4,8-Anhydro-9-O-(tert-butyldiphenylsilyl)-1-deoxy-5,6,7-tri-O-methyl-d-

glycero-d-talo-nono-2,3-diulosa (58): Prepared from 54 (50 mg,

0.103 mmol) following the general procedure (Method B) using NaIO₄

(88 mg, 0.412 mmol) and RuO₂·xH₂O (0.7 mg). The reaction mixture was

stirred at room temperature in the dark for 1 h. The residue was purified

by rapid silica gel column chromatography (hexanes/EtOAc 1:1) to give

58 (28 mg, 0.055 mmol, 53%) as a yellow oil: [a]_D= +16 cm³g^ꢁ1dm^ꢁ1

(c=1.50 in CHCl₃); ¹H NMR (400 MHz, C₆D₆): d=1.20 (s, 9H), 1.86 (s,

3H), 3.18 (s, 3H), 3.19 (s, 3H), 3.33 (s, 3H), 3.43 (dd, J=8.2, 3.2 Hz,

1H), 3.81 (dd, J=8.0, 8.0 Hz, 1H), 4.00 (dd, J=3.4, 3.4 Hz, 1H), 4.02–

4.06 (m, 3H), 5.28 (d, J=3.4 Hz, 1H), 7.21–7.89 ppm (m, 10H);

¹³C NMR (100.6 MHz, C₆D₆): d=19.6 (C), 24.0 (CH₃), 27.1 (3ꢆCH₃),

57.5 (CH₃), 57.7 (CH₃), 59.8 (CH₃), 63.8 (CH₂), 74.5 (CH), 75.8 (CH),

76.3 (CH), 78.2 (CH), 81.2 (CH), 128.1–132.6 (10ꢆCH), 133.9 (C), 134.2

(C), 198.2 (C), 198.9 ppm (C); IR (film): n˜ =2933, 1718 cm^ꢁ1; MS (ESI⁺):

m/z (%): 569 (100) [M⁺+MeOH+Na]; HRMS (ESI⁺): m/z: calcd for

C₂₉H₄₂NaO₈Si: 569.2547 [M⁺+MeOH+Na]; found: 569.2554; elemental

analysis calcd (%) for C₂₈H₃₈O₇Si (514.68): C 65.34, H 7.44; found: C

65.26, H 7.49.

Photolysis of 59:

A deoxygenated solution of diketone 59 (25 mg,

0.086 mmol) in dry C₆D₆(0.6 mL), was placed in a resonance tube and ir-

radiated with a daylight lamp at 308C. The reaction was monitored by

¹H NMR spectroscopy, complete consumption of starting material was

observed after 2 h, leading to exclusive formation of intermediate photo-

enol. The solution could be concentrated at low temperature under re-

duced pressure but the photoenol was not stable enough to withstand

chromatographic purification (silica gel or alumina). After silica gel

column chromatography (hexanes/EtOAc 40:60) only the known 2,3,4,6-

tetra-O-methyl-d-galactono-1,5-lactone^[46](16 mg, 0.068 mmol, 80%)

could be obtained.

4,8-Anhydro-9-O-(tert-butyldiphenylsilyl)-1-deoxy-5,6,7-tri-O-methyl-d-

glycero-l-gluco-nono-2,3-diulose (60): Prepared from 56 (50 mg,

0.104 mmol) following the general procedure (Method B) using NaIO₄

(89 mg, 0.416 mmol) and RuO₂·xH₂O (0.9 mg). The reaction mixture was

stirred at room temperature in the dark for 20 min. The residue was puri-

fied by rapid silica gel column chromatography (hexanes/EtOAc 4:6) to

Photocyclization of 58: A deoxygenated solution of diketone 58 (40 mg,

0.078 mmol) in dry C₆D₆(1 mL), was placed in a resonance tube and irra-

diated with a daylight lamp at 308C. The reaction was monitored by

¹H NMR spectroscopy, complete transformation of the starting material

was accomplished after 18 h. The solution was then heated at 508C in the

dark for 2 h, and concentrated under reduced pressure. The crude residue

in CH₂Cl₂(0.7 mL) was acetylated at 08C with Ac₂O (30 mL, 0.778 mmol)

and 4-dimethylaminopyridine (DMAP; 28 mg, 0.233 mmol) for 2 h. The

give 60 (34 mg, 0.066 mmol, 64%) as

a

yellow oil: [a]_D= +

61 cm³g^ꢁ1dm^ꢁ1(c=0.25 in CHCl₃); H NMR (500 MHz, CDCl₃): d=1.07

(s, 9H), 2.28 (s, 3H), 3.37 (s, 3H), 3.41 (dd, J=8.5, 2.6 Hz, 1H), 3.50 (s,

3H), 3.53 (s, 3H), 3.79 (d, J=2.4 Hz, 1H), 3.81 (d, J=1.1 Hz, 1H), 3.91

(dd, J=2.6, 2.4 Hz, 1H), 3.94 (dd, J=8.5, 6.9 Hz, 1H), 4.44 (m, 1H), 5.38

(d, J=6.9 Hz, 1H), 7.35–7.77 ppm (m, 10H); ¹³C NMR (100.6 MHz,

CDCl₃): d=19.2 (CH₃), 23.5 (C), 26.9 (3ꢆCH₃), 57.8 (CH₃), 59.5 (CH₃),

60.7 (CH₃), 61.2 (CH₂), 71.9 (CH), 74.6 (CH), 75.4 (CH), 78.4 (CH), 81.2

1

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16

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www.chemeurj.org

ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 0000, 00, 0 – 0

ÝÝ

These are not the final page numbers!

Synthesis of Polyhydroxylated Cyclopentitols

FULL PAPER

(CH), 127.7–135.6 (10ꢆCH), 133.3 (C), 133.4 (C), 197.0 (C), 200.1 ppm

(C); IR (film): n˜ =2936, 1716 cm^ꢁ1; MS (ESI⁺): m/z (%): 569 (100) [M⁺

+MeOH+Na]; HRMS (ESI⁺): m/z calcd for C₂₉H₄₂NaO₈Si: 569.2547

[M⁺+MeOH+Na]; found: 569.2556; elemental analysis calcd (%) for

C₂₈H₃₈O₇Si (514.68): C 65.34, H 7.44; found: C 65.49, H 7.36.

(%): 373 (100) [M⁺+MeOH+Na], 341 (21) [M⁺+Na]; HRMS (ESI⁺):

m/z: calcd for C₁₅H₂₆NaO₉: 373.1475 [M⁺+MeOH+Na]; found:

373.1465; elemental analysis calcd (%) for C₁₄H₂₂O₈(318.32): C 52.82, H

6.97; found: C 52.95, H 6.89.

Photocyclization of 61: A deoxygenated solution of diketone 61 (14 mg,

0.044 mmol) in dry C₆D₆(0.5 mL), was placed in a resonance tube and ir-

radiated with a daylight lamp at 308C. The reaction was monitored by

¹H NMR spectroscopy; complete transformation into the enol intermedi-

ate was observed after 2.5 h. The solution was heated at 708C in the dark

for 3 h and concentrated under reduced pressure. The residue was dis-

solved in CH₂Cl₂(0.4 mL), cooled at 08C, and acetylated with Ac₂O

(12 mL, 0.132 mmol) and DMAP (16 mg, 0.132 mmol). The solution was

stirred at room temperature for 2 h, concentrated under reduced pres-

sure, and the residue purified by silica gel column chromatography (hex-

anes/EtOAc 7:3) to give (2S,3aR,4S,5R,6R,6aS)-6a-(acetyloxy)methyl-

4,5,6-trimethoxy-2-methyl-3-oxohexahydro-2H-cyclopenta[b]furan-2-yl

acetate (66) and (2R,3aS,4S,5R,6R,6aR)-6a-(acetyloxy)methyl-4,5,6-trime-

thoxy-2-methyl-3-oxohexahydro-2H-cyclopenta[b]furan-2-yl acetate (65)

(12 mg, 0.033 mmol, d.r. 3:1, 76% from 61). The sensitive photoenol in-

termediate was detected by NMR spectroscopy but in this case could not

be obtained in pure state. Only clearly distinguished signals from the re-

Photocyclization of 60: A deoxygenated solution of diketone 60 (28 mg,

0.054 mmol) in dry C₆D₆(0.7 mL), was placed in a resonance tube and ir-

radiated with a daylight lamp at 308C. The reaction was monitored by

¹H NMR spectroscopy; complete transformation into the enol intermedi-

ate was observed after 2.5 h. The solution was heated at 608C in the dark

for 1.5 h and concentrated under reduced pressure. The residue was dis-

solved in CH₂Cl₂(0.6 mL), cooled at 08C, and acetylated with Ac₂O

(20 mL, 0.163 mmol) and DMAP (20 mg, 0.163 mmol). The solution was

stirred at room temperature for 2 h, concentrated under reduced pres-

sure, and the residue purified by silica gel column chromatography (hex-

anes/EtOAc 7:3) to give (2S,3aR,4S,5R,6R,6aS)-6a-[(tert-butyldiphenylsi-

lyl)oxy]methyl-4,5,6-trimethoxy-2-methyl-3-oxohexahydro-2H-cyclopen-

ta[b]furan-2-yl acetate (64) and (2R,3aS,4S,5R,6R,6aR)-6a-[(tert-butyldi-

phenylsilyl)oxy]methyl-4,5,6-trimethoxy-2-methyl-3-oxohexahydro-2H-cy-

clopenta[b]furan-2-yl acetate (63) (21 mg, 0.038 mmol, d.r. 2:1, 69%).

The sensitive photoenol intermediate was detected by NMR spectroscopy

but in this case could not be obtained in pure state. Only clearly distin-

guished signals from the reaction mixture are reported. ¹H NMR

(400 MHz, C₆D₆): d=1.25 (s, 9H), 1.85 (s, 3H), 2.89 (s, 3H), 3.13 (s, 3H),

3.15 (s, 3H), 4.68 (d, J=18.3 Hz, 1H), 4.74 (d, J=18.6 Hz, 1H), 5.54 (dd,

J=9.0, 1.1 Hz, 1H), 6.84 ppm (d, J=1.3 Hz, OH); ¹³C NMR (100.6 MHz,

C₆D₆): d=19.6 (C), 22.8 (CH₃), 27.0 (3ꢆCH₃), 57.0 (CH₃), 58.2 (CH₃),

59.9 (CH₃), 69.5 (CH₂), 111.7 (CH), 149.9 (C), 194.6 (C), 206.4 ppm (C).

1

action mixture are reported: H NMR (400 MHz, C₆D₆): d=1.79 (s, 3H),

1.87 (s, 3H), 3.13 (s, 3H), 3.14 (s, 3H), 3.24 (s, 3H), 4.92 (d, J=17.5 Hz,

1H), 5.07 (d, J=17.5 Hz, 1H), 5.52 (br d, J=9.3 Hz, 1H), 6.89 ppm (brs,

1H, OH); ¹³C NMR (100.6 MHz, C₆D₆): d=20.1 (CH₃), 22.7 (CH₃), 57.1

(CH₃), 58.7 (CH₃), 60.0 (CH₃), 67.7 (CH₂), 111.6 (CH), 150.0 (C), 169.8

(C), 194.6 (C), 202.7 ppm (C).

Compound 65: colorless oil, unstable, and decomposed on standing at

Compound 63: colorless oil. [a]_D= +14 cm³g^ꢁ1dm^ꢁ1(c=0.28 in CHCl₃);

¹H NMR (400 MHz, CDCl₃): d=1.08 (s, 9H), 1.54 (s, 3H), 1.87 (s, 3H),

3.27 (d, J=2.9 Hz, 1H), 3.36 (s, 3H), 3.45 (s, 3H), 3.48 (s, 3H), 3.70 (d,

J=10.3 Hz, 1H), 3.77 (dd, J=4.2, 4.2 Hz, 1H), 3.81 (dd, J=4.8, 2.9 Hz,

1H), 3.88 (d, J=10.1 Hz, 1H), 4.06 (d, J=4.0 Hz, 1H), 7.36–7.72 ppm

(m, 10H); ¹³C NMR (100.6 MHz, CDCl₃): d=19.3 (C), 20.7 (CH₃), 22.7

(CH₃), 26.8 (3ꢆCH₃), 53.3 (CH), 57.7 (CH₃), 57.8 (CH₃), 59.9 (CH₃), 65.4

(CH₂), 81.2 (CH), 83.3 (CH), 83.9 (CH), 89.2 (C), 102.0 (C), 127.7–135.7

(10ꢆCH), 132.97 (C), 133.00 (C), 169.8 (C), 207.4 ppm (C); IR (film):

n˜ =2930, 1766, 1745 cm^ꢁ1; MS (ESI⁺): m/z (%): 579 (100) [M⁺+Na];

HRMS (ESI⁺): m/z calcd for C₃₀H₄₀NaO₈Si: 579.2390 [M⁺+Na]; found:

579.2393; elemental analysis calcd (%) for C₃₀H₄₀O₈Si (556.72): C 64.72,

H 7.24; found: C 64.75, H 7.16.

room temperature preventing us from obtaining good 1D and 2D NMR

1

spectra. [a]_D= +15 cm³g^ꢁ1dm^ꢁ1(c=0.56 in CHCl₃); H NMR (500 MHz,

CDCl₃): d=1.57 (s, 3H), 2.04 (s, 3H), 2.11 (s, 3H), 3.29 (d, J=2.8 Hz,

1H), 3.34 (s, 3H), 3.43 (s, 3H), 3.51 (s, 3H), 3.71 (dd, J=4.1, 4.1 Hz,

1H), 3.76 (d, J=4.1 Hz, 1H), 3.82 (dd, J=4.1, 2.8 Hz, 1H), 4.20 (d, J=

11.7 Hz, 1H), 4.43 ppm (d, J=11.7 Hz, 1H); ¹³C NMR (125.7 MHz,

CDCl₃): d=21.7 (CH₃), 21.86 (CH₃), 21.9 (CH₃), 54.5 (CH), 58.5 (CH₃),

58.7 (CH₃), 60.7 (CH₃), 67.4 (CH₂), 83.2 (CH), 83.8 (CH), 83.9 ppm

(CH), (quaternary carbons not observed); IR (film): n˜ =2922, 1766, 1742,

1731 cm^ꢁ1; MS (ESI⁺): m/z (%): 383 (100) [M⁺+Na]; HRMS (ESI⁺): m/

z calcd for C₁₆H₂₄NaO₉: 383.1318 [M⁺+Na]; found: 383.1322; elemental

analysis calcd (%) for C₁₆H₂₄O₉(360.36): C 53.33, H 6.71; found: C 53.43,

H 6.46.

Compound 66: colorless oil. [a]_D= +25 cm³g^ꢁ1dm^ꢁ1(c=0.56 in CHCl₃);

¹H NMR (500 MHz, CDCl₃): d=1.54 (s, 3H), 2.05 (s, 3H), 2.09 (s, 3H),

3.26 (d, J=9.1 Hz, 1H), 3.47 (s, 3H), 3.48 (s, 3H), 3.56 (s, 3H), 3.68 (dd,

J=6.9, 4.1 Hz, 1H), 3.82 (d, J=3.8 Hz, 1H), 4.04 (dd, J=9.1, 6.9 Hz,

1H), 4.18 (d, J=11.7 Hz, 1H), 4.69 ppm (d, J=11.7 Hz, 1H); ¹³C NMR

(125.7 MHz, CDCl₃): d=20.8 (CH₃), 20.9 (CH₃), 21.7 (CH₃), 50.4 (CH),

58.8 (CH₃), 59.2 (CH₃), 60.6 (CH₃), 64.1 (CH₂), 83.1 (CH), 83.2 (CH),

85.2 (CH), 89.6 (C), 101.7 (C), 169.8 (C), 170.4 (C), 205.0 ppm (C); IR

(film): n˜ =2938, 1768, 1744 cm^ꢁ1; MS (ESI⁺): m/z (%): 383 (100) [M⁺

+Na]; HRMS (ESI⁺): m/z calcd for C₁₆H₂₄NaO₉: 383.1318 [M⁺+Na];

found: 383.1324; elemental analysis calcd (%) for C₁₆H₂₄O₉(360.36): C

53.33, H 6.71; found: C 53.35, H 6.68.

Compound 64: colorless oil; [a]_D= +29 cm³g^ꢁ1dm^ꢁ1(c=0.38 in CHCl₃);

¹H NMR (500 MHz, CDCl₃): d=1.06 (s, 9H), 1.59 (s, 3H), 1.63 (s, 3H),

3.14 (d, J=9.5 Hz, 1H), 3.47 (s, 3H), 3.50 (s, 3H), 3.58 (s, 3H), 3.71 (dd,

J=8.2, 3.5 Hz, 1H), 3.92 (d, J=11.0 Hz, 1H), 3.94 (d, J=3.5 Hz, 1H),

4.00 (d, J=11.4 Hz, 1H), 4.07 (dd, J=9.5, 8.2 Hz, 1H), 7.35–7.72 ppm

(m, 10H); ¹³C NMR (125.7 MHz, CDCl₃): d=19.4 (C), 20.8 (CH₃), 22.0

(CH₃), 26.9 (3ꢆCH₃), 49.6 (CH), 58.9 (CH₃), 59.2 (CH₃), 60.9 (CH₃), 64.9

(CH₂), 82.0 (CH), 83.8 (CH), 85.7 (CH), 92.2 (C), 101.9 (C), 127.6–137.8

(10ꢆCH), 129.59 (C), 129.60 (C), 169.5 (C), 205.5 ppm (C); IR (film):

n˜ =2923, 1766, 1747 cm^ꢁ1; MS (ESI⁺): m/z (%): 579 (100) [M⁺+Na];

HRMS (EI): m/z calcd for C₃₀H₄₀NaO₈Si: 579.2490 [M⁺+Na]; found:

579.2401; elemental analysis calcd (%) for C₃₀H₄₀O₈Si (556.72): C 64.72,

H 7.24; found: C 64.35, H 7.11.

4,7-Anhydro-8-O-tert-butyldiphenylsilyl-1-deoxy-5,6-O-isopropylidene-d-

altro-octo-2,3-diulosa (70): Prepared from 67 (27 mg, 0.057 mmol) follow-

ing the general procedure (Method B) using NaIO₄(37 mg, 0.171 mmol)

and RuO₂·xH₂O (0.3 mg). The reaction mixture was stirred at room tem-

perature in the dark for 50 min. The residue was purified by rapid silica

gel column chromatography (hexanes/EtOAc 97:3) to give 70 (19 mg,

0.039 mmol, 69%) as a yellow oil and the known lactone 73^[47](2 mg,

0.005 mmol, 6%).

Compound 70: [a]_D=ꢁ4 cm³g^ꢁ1dm^ꢁ1(c=1.01 in CHCl₃); ¹H NMR

(500 MHz, CDCl₃): d=1.09 (s, 9H), 1.27 (s, 3H), 1.36 (s, 3H), 2.37 (s,

3H), 3.70 (dd, J=11.4, 2.5 Hz, 1H), 3.88 (dd, J=11.4, 3.5 Hz, 1H), 4.35

(dd, J=2.8, 2.8 Hz, 1H), 4.82 (d, J=6.0 Hz, 1H), 5.31 (dd, J=5.7, 5.7 Hz,

1H), 5.57 (d, J=5.4 Hz, 1H), 7.38–7.65 ppm (m, 10H); ¹H NMR

(500 MHz, C₆D₆): d=1.08 (s, 3H), 1.13 (s, 9H), 1.35 (s, 3H), 1.99 (s, 3H),

3.39 (dd, J=11.0, 3.2 Hz, 1H), 3.66 (dd, J=11.4, 3.5 Hz, 1H), 4.31 (dd,

9-O-Acetyl-4,8-anhydro-1-deoxy-5,6,7-tri-O-methyl-d-glycero-l-gluco-

nono-2,3-diulose (61): Prepared from 57 (70 mg, 0.244 mmol) following

the general procedure (Method B) using NaIO₄(156 mg, 0.732 mmol)

and RuO₂·xH₂O (1.2 mg). The reaction mixture was stirred at room tem-

perature in the dark for 40 min. The residue was purified by rapid silica

gel column chromatography (hexanes/EtOAc 4:6) to give 61 (37 mg,

0.116 mmol, 48%) as a yellow oil. [a]_D= +82 cm³g^ꢁ1dm^ꢁ1(c=0.71 in

CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=2.05 (s, 3H), 2.28 (s, 3H), 3.34

(s, 3H), 3.47 (m, 1H), 3.48 (s, 3H), 3.49 (s, 3H), 3.72 (dd, J=3.2, 3.2 Hz,

1H), 3.98 (dd, J=6.9, 5.0 Hz, 1H), 4.15 (dd, J=12.0, 3.5 Hz, 1H), 4.42–

4.51 (m, 2H), 5.39 ppm (d, J=5.4 Hz, 1H); ¹³C NMR (100.6 MHz, C₆D₆):

d=20.8 (CH₃), 23.7 (CH₃), 58.4 (CH₃), 59.1 (CH₃), 59.6 (CH₃), 61.7

(CH₂), 71.6 (CH), 73.4 (CH), 75.2 (CH), 77.9 (CH), 78.7 (CH), 170.9 (C),

197.1 (C), 198.5 ppm (C); IR (film): n˜ =2936, 1739 cm^ꢁ1; MS (ESI⁺): m/z

Chem. Eur. J. 2013, 00, 0 – 0

ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

&

17

&

ÞÞ

These are not the final page numbers!

E. I. Leon, E. Suꢄrez et al.

J=3.5, 2.8 Hz, 1H), 4.65 (d, J=6.2, 1.1 Hz, 1H), 5.31 (dd, J=5.7, 5.7 Hz,

1H), 5.66 (d, J=5.4 Hz, 1H), 7.19–7.70 ppm (m, 10H); ¹³C NMR

(100.4 MHz, CDCl₃): d=19.1 (C), 23.6 (CH₃), 24.8 (CH₃), 25.7 (CH₃),

26.9 (3ꢆCH₃), 65.9 (CH₂), 82.7 (CH), 83.1 (CH), 84.7 (CH), 85.4 (CH),

113.3 (C), 127.9 (4ꢆCH), 129.9 (CH), 130.0 (CH), 132.5 (C), 132.6 (C),

135.5 (2ꢆCH), 135.6 (2 ꢆ CH), 192.2 (C), 197.7 ppm (C); ¹³C NMR

(100.4 MHz, C₆D₆): d=19.2 (C), 23.1 (CH₃), 24.9 (CH₃), 26.0 (CH₃), 27.0

(3ꢆCH₃), 65.9 (CH₂), 83.2 (CH), 83.5 (CH), 84.9 (CH), 85.2 (CH), 113.5

(C), 128.18 (2ꢆCH), 128.21 (2ꢆCH), 130.18, (CH), 130.20 (CH), 133.2

(C), 133.3 (C), 135.9 (2ꢆCH), 136.0 (2ꢆCH), 191.7 (C), 197.4 ppm (C);

IR (CHCl₃, 0.2 mm): n˜ =2936, 1717 cm^ꢁ1; MS (ESI⁺): m/z (%): 537 (100)

[M⁺+MeOH+Na], 505 (72) [M⁺+Na]; HRMS (ESI⁺): m/z calcd for

C₂₈H₃₈O₇NaSi: 537.2285 [M⁺+MeOH+Na]; found: 537.2288; calcd for

C₂₇H₃₄NaO₆Si [M⁺+Na]: 505.2022; found: 505.2025; elemental analysis

calcd (%) for C₂₇H₃₄O₆Si (482.64): C 67.19, H 7.10; found: C 67.32, H

7.11.

MS (ESI⁺): m/z (%): 537 (100) [M⁺+MeOH+Na], 505 (38) [M⁺+Na];

HRMS (ESI⁺): m/z calcd for C₂₈H₃₈O₇NaSi: 537.2285 [M⁺

+MeOH+Na]; found: 537.2293; calcd for C₂₇H₃₄NaO₆Si [M⁺+Na]:

505.2022; found: 505.2033; elemental analysis calcd (%) for C₂₇H₃₄O₆Si

(482.64): C 67.19, H 7.10; found: C 67.38, H 7.38.

Photolysis of 71:

A deoxygenated solution of diketone 71 (29 mg,

0.061 mmol) in dry C₆D₆(0.6 mL), was placed in a resonance tube and ir-

radiated with a daylight lamp at 308C for 2 h. The reaction was moni-

tored by ¹H NMR spectroscopy, leading to exclusive formation of the

photoenol mixture 74a (3:5). The mixture was concentrated under re-

duced pressure and the residue purified by silica gel column chromatog-

raphy (hexanes/EtOAc 9:1) to give the known lactone 73 (12 mg,

0.028 mmol, 64%) from the oxidation of the photoenol by oxygen.

4,7-Anhydro-8-O-tert-butyldiphenylsilyl-1-deoxy-5,6-O-isopropylidene-d-

talo-octo-2,3-diulose (72): Prepared from 69 (70 mg, 0.160 mmol) follow-

ing the general procedure (Method B) using NaIO₄(116 mg, 0.540 mmol)

and RuO₂·xH₂O (1 mg). The reaction mixture was stirred at room tem-

perature in the dark for 3 h. The residue was purified by rapid silica gel

column chromatography (hexanes/EtOAc 9:1) to give 72 (30 mg,

0.062 mmol, 39%) as a yellow oil. [a]_D= +3 cm³g^ꢁ1dm^ꢁ1(c=1.14 in

CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=1.05 (s, 9H), 1.32 (s, 3H), 1.42

(s, 3H), 2.37 (s, 3H), 3.93 (dd, J=10.4, 6.3 Hz, 1H), 3.99 (dd, J=10.4,

6.0 Hz, 1H), 4.08 (ddd, J=6.0, 6.0, 3.5 Hz, 1H), 4.73 (dd, J=6.0, 3.5 Hz,

1H), 4.94 (dd, J=6.0, 1.3 Hz, 1H), 5.10 (br s, 1H), 7.33–7.71 ppm (m,

10H); ¹³C NMR (125.7 MHz, CDCl₃): d=19.2 (C), 24.5 (CH₃), 25.3

(CH₃), 26.3 (CH₃), 26.8 (3ꢆCH₃), 61.8 (CH₂), 80.8 (CH), 82.1 (CH), 83.2

(CH), 84.4 (CH), 113.3 (C), 127.58 (2ꢆCH), 127.63 (2ꢆCH), 129.6 (2ꢆ

CH), 133.5 (C), 133.6 (C), 135.67 (2ꢆCH), 135.71 (2ꢆCH), 195.6 (C),

198.1 ppm (C); ¹H NMR (500 MHz, C₆D₆): d=1.12 (s, 3H), 1.19 (s, 9H),

1.32 (s, 3H), 1.80 (s, 3H), 4.14–4.25 (m, 3H), 4.35 (dd, J=6.0, 3.5 Hz,

1H), 4.69 (dd, J=6.0, 1.3 Hz, 1H), 5.16 (br s, 1H), 7.21–7.85 (m, 10H);

¹³C NMR (100.6 MHz, C₆D₆): d=19.5 (C), 23.7 (CH₃), 25.2 (CH₃), 26.4

(CH₃), 27.0 (3ꢆCH₃), 62.5 (CH₂), 81.2 (CH), 82.7 (CH), 83.6 (CH), 84.7

(CH), 113.1 (C), 127.97 (2ꢆCH), 128.0 (2ꢆCH), 129.93 (2ꢆCH), 133.9

(C), 134.0 (C), 136.06 (2ꢆCH), 136.12 (2ꢆCH), 195.8 (C), 197.5 ppm

(C); IR (CHCl₃, 0.2 mm): n˜ =2933, 1719 cm^ꢁ1; MS (ESI⁺): m/z (%): 537

(100) [M⁺+MeOH+Na]; 505 (39) [M⁺+Na]; HRMS (ESI⁺): m/z calcd

for C₂₈H₃₈NaO₇Si [M⁺+MeOH+Na]: 537.2285; found: 537.2287; calcd

for C₂₇H₃₄NaO₆Si [M⁺+Na]: 505.2022; found: 505.2027; elemental analy-

sis calcd (%) for C₂₇H₃₄O₆Si (482.64): C 67.19, H 7.10; found: C 66.80, H

7.51.

Photolysis of 70:

A deoxygenated solution of diketone 70 (21 mg,

0.044 mmol) in dry C₆D₆(0.6 mL), was placed in a resonance tube and ir-

radiated with a daylight lamp at 308C for 2 h. The reaction was moni-

tored by ¹H NMR spectroscopy, leading to exclusive formation of the

photoenol mixture 74a (4:1). The mixture was concentrated under re-

duced pressure and the residue purified by silica gel column chromatog-

raphy (hexanes/EtOAc 9:1) to give known lactone 73 (17 mg,

0.040 mmol, 65%) from the oxidation of the photoenol by oxygen.

Compound 74a: ¹H NMR (500 MHz, C₆D₆;): d (major isomer)=0.99 (s,

9H), 1.23 (s, 3H), 1.36 (s, 3H), 2.46 (s, 3H), 3.22 (dd, J=11.3, 2.2 Hz,

1H), 3.58 (dd, J=11.4, 2.5 Hz, 1H), 4.39 (m, 1H), 4.68 (d, J=6.3 Hz,

1H), 5.62 (d, J=6.3 Hz, 1H), 6.42 (brs, 1H), 7.18–7.68 ppm (m, 10H); d

(minor isomer)=1.00 (s, 9H), 1.27 (s, 3H), 1.46 (s, 3H), 2.37 (s, 3H),

3.26 (dd, J=11.4, 2.5 Hz, 1H), 3.41 (dd, J=11.4, 2.5 Hz, 1H), 4.39 (m,

1H), 4.60 (d, J=6.2 Hz, 1H), 5.76 (d, J=6.0 Hz, 1H), 6.06 (br s, 1H),

7.18–7.68 ppm (m, 10H); ¹³C NMR (125.7 MHz, CDCl₃;):

d (major

isomer)=19.1 (C), 25.9 (CH₃), 26.1 (CH₃), 26.74 (3ꢆCH₃), 26.9 (CH₃),

65.0 (CH₂), 80.6 (CH), 81.8 (CH), 87.3 (CH), 112.7 (C), 130.4–136.0 (10ꢆ

CH), 132.5 (C), 133.1 (C), 133.2 (C), 152.2 (C), 191.9 ppm (C); d (minor

isomer)=19.1 (C), 25.6 (CH₃), 25.7 (CH₃), 26.7 (3ꢆCH₃), 26.8 (CH₃),

65.1 (CH₂), 80.8 (CH), 82.0 (CH), 89.1 (CH), 112.9 (C), 130.35–135.99

(10ꢆCH), 132.5 (C), 133.0 (C), 133.2 (C), 152.3 (C), 192.2 ppm (C).

4,7-Anhydro-8-O-tert-butyldiphenylsilyl-1-deoxy-5,6-O-isopropylidene-d-

allo-octo-2,3-diulose (71): Prepared from 68 (47 mg, 0.102 mmol) follow-

ing the general procedure (Method B) using NaIO₄(73 mg, 0.340 mmol)

and RuO₂·xH₂O (0.6 mg). The reaction mixture was stirred at room tem-

perature in the dark for 2 h. The residue was purified by rapid silica gel

column chromatography (hexanes/EtOAc 97:3) to give 71 as a yellow oil

(33 mg, 0.069 mmol, 68%) and the known lactone 73 (3 mg, 0.007 mmol,

6%). [a]_D=ꢁ2 cm³g^ꢁ1dm^ꢁ1(c=1.88 in CHCl₃); ¹H NMR (500 MHz,

C₆D₆, 308C; conformer A): d=1.17 (s, 9H), 1.18 (s, 3H), 1.47 (s, 3H),

1.82 (s, 3H), 3.72 (m, 2H), 4.24 (dd, J=9.8, 5.0 Hz, 1H), 4.46 (d, J=

2.5 Hz, 1H), 4.67 (dd, J=6.3, 4.7 Hz, 1H), 5.00 (dd, J=6.6, 3.5 Hz, 1H),

7.21–7.78 (m, 10H); conformer B: d=1.13 (s, 9H), 1.17 (s, 3H), 1.46 (s,

3H), 2.04 (s, 3H), 3.74 (dd, J=11.0, 5.4 Hz, 1H), 3.81 (dd, J=11.0,

4.7 Hz, 1H), 4.33 (m, 1H), 4.63 (dd, J=6.3, 3.2 Hz, 1H), 4.86 (dd, J=6.3,

3.5 Hz, 1H), 5.18 (d, J=3.5 Hz, 1H), 7.21–7.78 ppm (m, 10H); ¹H NMR

(500 MHz, C₆D₆, 708C): d=1.14 (s, 9H), 1.19 (s, 3H), 1.45 (s, 3H), 1.86

(s, 3H), 3.74 (dd, J=11.0, 5.4 Hz, 1H), 3.78 (dd, J=11.0, 5.1 Hz, 1H),

4.30 (m, 1H), 4.65 (dd, J=6.3, 3.2 Hz, 1H), 4.86 (dd, J=6.3, 3.5 Hz, 1H),

5.10 (d, J=3.5 Hz, 1H), 7.22–7.76 ppm (m, 10H); ¹³C (100.6 MHz, C₆D₆,

308C): d (conformer A)=19.4 (C), 24.0 (CH₃), 25.5 (CH₃), 27.03 (CH₃),

27.4 (3ꢆCH₃), 64.4 (CH₂), 82.4 (CH), 82.7 (CH), 85.7 (CH), 86.5 (CH),

114.1 (C), 128.1–136.0 (10ꢆCH), 133.57–133.64 (2ꢆC), 195.3 (C),

197.3 ppm (C); d (conformer B)=19.4 (C), 23.1 (CH₃), 25.4 (CH₃), 27.0

(CH₃), 27.6 (3ꢆCH₃), 64.7 (CH₂), 81.6 (CH), 82.0 (CH), 86.3 (CH), 86.9

(CH), 114.1 (C), 128.1–136.0 (10ꢆCH), 133.67–133.64 (2ꢆC), 195.3 (C),

197.3 ppm (C); ¹³C NMR (125.7 MHz, C₆D₆, 708C): d=19.5 (C), 24.0

(CH₃), 25.6 (CH₃), 27.2 (CH₃), 27.4 (3ꢆCH₃), 64.6 (CH₂), 82.6 (CH), 82.9

(CH), 85.6 (CH), 86.8 (CH), 114.3 (C), 128.09 (2ꢆCH), 128.10 (2ꢆCH),

130.05 (CH), 130.06 (CH), 133.9 (C), 134.0 (C), 136.04 (4ꢆCH), 195.7

Photolysis of 72: A deoxygenated solution of diketone 72 (42.7 mg,

0.09 mmol) in purified CDCl₃(1 mL), was placed in a resonance tube

and irradiated with a daylight lamp at 308C for 9 h. The reaction was

1

monitored by H NMR spectroscopy, leading to exclusive formation of 75

besides a small amount of photoenol intermediate 74b. The mixture was

kept at room temperature in the dark for 14 h for the complete transfor-

mation of 74b into 75. The solution could be concentrated at low temper-

ature under reduced pressure to give 75 (41.4 mg) as a hemiketal mixture

(10:8). Compound 75 was not stable enough to withstand chromatograph-

ic purification (silica gel or alumina). Notwithstanding, the crude residue

(colorless oil) was pure enough to allow the complete analytical and

spectroscopic characterization.

1

Photoenol 74b: H NMR (400 MHz, CDCl₃): d=2.25 (s, 3H), 4.26 (d, J=

18.8 Hz, 1H), 4.39 (d, J=18.5 Hz, 1H), 4.96 (d, J=7.4 Hz, 1H), 5.37 (dd,

J=8.5, 1.3 Hz, 1H), 5.51 (dd, J=8.7, 7.4 Hz, 1H), 6.71 (brd, J=1.6 Hz,

1H).

Compound 75: ¹H (400 MHz, CDCl₃; major isomer): d=1.11 (s, 9H),

1.33 (s, 3H), 1.43 (s, 3H), 2.30 (s, 3H), 3.90 (d, J=10.6 Hz, 1H), 4.02 (d,

J=10.6 Hz, 1H), 4.17 (dd, J=5.8, 1.3 Hz, 1H), 4.87 (dd, J=5.8, 3.2 Hz,

1H), 5.95 (dd, J=3.3, 1.2 Hz, 1H), 7.35–7.76 ppm (m, 10H); d (minor

isomer)=1.08 (s, 9H), 1.33 (s, 3H), 1.43 (s, 3H), 2.31 (s, 3H), 3.85 (s,

2H), 4.30 (d, J=6.6 Hz, 1H), 4.70 (dd, J=6.4, 4.0 Hz, 1H), 6.16 (d, J=

4.0 Hz, 1H), 7.35–7.76 ppm (m, 10H); ¹³C NMR (100.6 MHz, CDCl₃): d

(major isomer)=19.2 (C), 25.9 (CH₃), 26.5 (CH₃), 26.7 (CH₃), 26.80 (3ꢆ

CH₃), 66.8 (CH₂), 69.3 (CH), 73.3 (CH), 98.0 (C), 107.6 (CH), 110.8 (C),

127.6–135.7 (10ꢆCH), 132.4 (C), 132.5 (C), 146.7 (C), 194.61 ppm (C); d

(minor isomer)=19.3 (C), 25.5 (CH₃), 26.78 (3ꢆCH₃), 65.7 (CH₂), 68.7

(C), 197.5 ppm (C); IR (CHCl₃, 0.2 mm): n<ꢄ= > =2936, 1721 cm^ꢁ1

;

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18

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ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 0000, 00, 0 – 0

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Synthesis of Polyhydroxylated Cyclopentitols

FULL PAPER

(CH), 72.1 (CH), 97.2 (C), 105.1 (CH), 109.7 (C), 127.6–135.7 (10ꢆCH),

132.6 (C), 132.7 (C), 149.0 (C), 194.57 ppm (C) (isopropylidene methyl

atoms not observed); UV/Vis (CH₂Cl₂): l_max(e)=262 nm (sh)

(2253 mol^ꢁ1m³cm^ꢁ1), 259 nm (2374 mol^ꢁ1m³cm^ꢁ1), 256 nm (sh)

(2274 mol^ꢁ1m³cm^ꢁ1), 228 nm (5844 mol^ꢁ1m³cm^ꢁ1); IR (CHCl₃, 0.2 mm):

n˜ =3520, 2936, 1790, 1727, 1710 cm^ꢁ1; MS (ESI⁺): m/z (%): 505 (100)

[M⁺+Na]; HRMS (ESI⁺): m/z calcd for C₂₇H₃₄NaO₆Si: 505.2022 [M⁺

+Na]; found: 505.2019; elemental analysis calcd (%) for C₂₇H₃₄O₆Si

(482.64): C 67.19, H 7.10; found: C 67.19, H 6.98.

(d, J=11.7 Hz, 1H), 4.74 (d, J=11.7 Hz, 1H), 7.19–7.4 (m, 21H), 7.65–

7.69 ppm (m, 4H); ¹³C NMR (125.7 MHz, CDCl₃): d=19.3 (C), 21.6

(CH₃), 26.8 (3ꢆCH₃), 51.6 (CH), 51.8 (CH₃), 62.8 (CH₂), 72.7 (CH₂), 72.8

(CH₂), 73.7 (CH₂), 82.2 (CH), 85.2 (CH), 86.5 (C), 86.7 (CH), 127.4

(CH), 127.5 (3ꢆCH), 127.6 (CH), 127.62 (4ꢆCH), 127.7 (2ꢆCH), 127.9

(2ꢆCH), 128.2 (2ꢆCH), 128.27 (2ꢆCH), 128.31 (2ꢆCH), 129.6 (CH),

129.7 (CH), 135.79 (2ꢆCH), 135.8 (2ꢆCH), 132.9 (C), 138.2 (C), 138.4

(C), 138.6 (C), 169.6 (C), 170.9 ppm (C); IR (CHCl₃, 0.2 mm): n˜ =2929,

1745 cm^ꢁ1; MS (FAB): m/z (%): 795 (10) [M⁺+Na]; HRMS (FAB): m/z

calcd for C₄₇H₅₂NaO₈Si, 795.3329 [M⁺+Na]; found: 795.3303; elemental

analysis calcd for C₄₇H₅₂O₈Si (772.99): C 73.03, H 6.78; found: C 73.16, H

6.99.

Methyl

(1S,2R,3S,4R,5S)-2-acetyloxy-3,4,5-trimethoxy-2-(methoxyme-

thyl)cyclopentane-1-carboxylate (76): H₅IO₆(23 mg, 0.101 mmol) was

added to a solution of 2 (17 mg, 0.059 mmol) in MeOH (3.5 mL). The

mixture was stirred for 2 h at room temperature and concentrated under

reduced pressure. A solution of the residue in Et₂O was treated with di-

azomethane at 08C. The mixture was then concentrated under reduced

pressure and the residue purified by silica gel column chromatography

(hexanes/EtOAc 7:3) to give 76 (16 mg, 0.05 mmol, 85%) as a colorless

oil: [a]_D= +32 cm³g^ꢁ1dm^ꢁ1(c=1.35 in CHCl₃); ¹H NMR (500 MHz,

CDCl₃): d=1.99 (s, 3H), 3.13 (d, J=8.8 Hz, 1H), 3.35 (s, 3H), 3.42 (s,

3H), 3.46 (s, 3H), 3.48 (s, 3H), 3.51 (dd, J=5.7, 5.0 Hz, 1H), 3.70 (s,

3H), 3.77 (d, J=9.5 Hz, 1H), 3.89 (brd, J=5.1 Hz, 1H), 3.94 (d, J=

9.8 Hz, 1H), 4.09 ppm (ddd, J=8.8, 5.7, 0.6 Hz, 1H); ¹³C NMR

(100.6 MHz, CDCl₃): d=21.7 (CH₃), 51.9 (CH), 52.2 (CH₃), 58.0 (CH₃),

58.3 (CH₃), 58.9 (CH₃), 59.3 (CH₃), 70.5 (CH₂), 84.7 (CH), 86.8 (CH),

86.9 (C), 88.6 (CH), 169.8 (C), 170.7 ppm (C); IR (film): n˜ =3013, 2936,

1740 cm^ꢁ1; MS (EI): m/z (%): 321 (<1) [M⁺+H], 260 (2); HRMS (EI):

m/z calcd for C₁₄H₂₅O₈: 321.1549; found [M⁺+H]: 321.1558; elemental

analysis calcd (%) for C₁₄H₂₄O₈(320.33): C 52.49, H 7.55; found: C 52.27,

H 7.49.

Methyl (1S,2R,3S,5R)-2-(acetyloxy)-3,5-dimethoxy-2-(methoxymethyl)cy-

clopentane-1-carboxylate (80): Method A: A solution of 46 (20.0 mg,

0.08 mmol) in MeOH (5 mL) containing H₅IO₆(35.4 mg, 0.16 mmol) was

stirred at room temperature for 5 h. The mixture was concentrated under

reduced pressure and the residue purified by silica gel column chroma-

tography (EtOAc!EtOAc/MeOH 95:5) to give acid 79 (19.9 mg,

0.072 mmol, 90%) as a colorless oil. [a]_D= +16 cm³g^ꢁ1dm^ꢁ1(c=0.55 in

CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=1.80 (ddd, J=14.2, 5.0, 5.0 Hz,

1H), 2.02 (s, 3H), 2.31 (ddd, J=14.2, 7.3, 5.6 Hz, 1H), 3.15 (d, J=6.3 Hz,

1H), 3.29 (s, 3H), 3.39 (s, 3H), 3.53 (s, 3H), 3.89 (d, J=10.7 Hz, 1H),

4.19 (dd, J=5.4, 5.0 Hz, 1H), 4.46 (m, 1H), 4.47 ppm (d, J=11.0 Hz,

1H); ¹³C NMR (125.7 MHz, CDCl₃): d=21.7 (CH₃), 34.3 (CH₂), 57.6

(CH₃), 57.8 (CH₃), 59.6 (CH₃), 60.0 (CH), 73.4 (CH₂), 80.7 (CH), 84.1

(CH), 89.2 (C), 169.2 (C), 169.9 ppm (C); IR (film): n˜ =3490, 2935,

1743 cm^ꢁ1; MS (ESI⁺): m/z (%): 299 (100) [M⁺+Na]; HRMS (ESI⁺):

m/z calcd for C₁₂H₂₀O₇Na: 299.1107 [M⁺+Na]; found: 299.1112; elemen-

tal analysis calcd (%) for C₁₂H₂₀O₇(276.28): C 52.17, H 7.30; found: C

52.12, H 7.39.

Methyl (1S,2R,3S,4R,5S)-2-acetyloxy-3,4,5-tris(benzyloxy)-2-(benzyloxy-

methyl)cyclopentane-1-carboxylate (77): H₅IO₆(12 mg, 0.054 mmol) was

added to a solution of 25 (16 mg, 0.027 mmol) in MeOH (1.6 mL). The

mixture was stirred for 1.5 h at room temperature and concentrated

under reduced pressure. A solution of the residue in Et₂O (0.5 mL) was

treated with diazomethane at 08C. The mixture was then concentrated

under reduced pressure and the residue purified by silica gel column

chromatography (hexanes/EtOAc 90:10) to give 77 (11 mg, 0.018 mmol,

65%) as a colorless oil: [a]_D= +14 cm³g^ꢁ1dm^ꢁ1(c=0.52 in CHCl₃);

¹H NMR (500 MHz, CDCl₃): d=1.95 (s, 3H), 3.37 (d, J=8.8 Hz, 1H),

3.63 (s, 3H), 3.94 (d, J=9.5 Hz, 1H), 3.96 (dd, J=5.5, 5.5 Hz, 1H), 4.12

(d, J=9.8 Hz, 1H), 4.29 (brd, J=5.1 Hz, 1H), 4.48 (dd, J=8.8, 6.0 Hz,

1H), 4.49 (d, J=12.6 Hz, 1H), 4.52 (d, J=12.0 Hz, 1H), 4.55 (d, J=

11.7 Hz, 1H), 4.58 (d, J=11.7 Hz, 1H), 4.61 (d, J=11.7 Hz, 1H), 4.63 (d,

J=11.4 Hz, 1H), 4.65 (d, J=11.4 Hz, 1H), 4.69 (d, J=11.7 Hz, 1H),

7.23–7.31 ppm (m, 20H); ¹³C NMR (125.7 MHz, CDCl₃): d=21.7 (CH₃),

51.9 (CH₃), 52.7 (CH), 68.7 (CH₂), 72.4 (CH₂), 72.8 (CH₂), 73.2 (CH₂),

73.4 (CH₂), 83.4 (CH), 85.2 (CH), 87.0 (C), 87.1 (CH), 127.39 (CH),

127.43 (2ꢆCH), 127.55 (CH), 127.58 (CH), 127.66 (3ꢆCH), 127.74 (2ꢆ

CH), 127.8 (2ꢆCH), 128.2 (2ꢆCH), 128.25 (2ꢆCH), 128.3 (4ꢆCH),

138.1 (C), 138.2 (2ꢆC), 138.3 (C), 169.9 (C), 170.7 ppm (C); IR (film):

n˜ =2928, 1738 cm^ꢁ1; MS (FAB): m/z (%): 647 (5) [M⁺+Na]; HRMS

(FAB): m/z: calcd for C₃₈H₄₀NaO₈: 647.2621 [M⁺+Na]; found: 647.2651;

elemental analysis calcd (%) for C₃₈H₄₀O₈(624.72): C 73.06, H 6.45;

found: C 72.65, H 6.82.

Method A and subsequent diazomethane esterification: A solution of 46

(19 mg, 0.072 mmol) in MeOH (4.5 mL) containing H₅IO₆(33 mg,

0.145 mmol) was stirred at room temperature for 6 h. The mixture was

concentrated under reduced pressure and the residue esterified with a

solution of diazomethane in Et₂O at 08C. The solvent was eliminated and

the residue purified by silica gel column chromatography (hexanes/

EtOAc 80:20) to give 80 (14 mg, 0.048 mmol, 67%) as a colorless oil:

1

[a]_D= +35 cm³g^ꢁ1dm^ꢁ1(c=0.87 in CHCl₃); H NMR (500 MHz, CDCl₃):

d=1.98 (s, 3H), 1.71 (ddd, J=14.5, 3.8, 3.8 Hz, 1H), 2.40 (ddd, J=14.2,

8.2, 6.0 Hz, 1H), 3.04 (d, J=7.3 Hz, 1H), 3.29 (s, 3H), 3.33 (s, 3H), 3.37

(s, 3H), 3.69 (s, 3H), 3.84 (d, J=10.1 Hz, 1H), 3.91 (dd, J=6.0, 3.5 Hz,

1H), 4.19 (d, J=10.1 Hz, 1H), 4.30 ppm (ddd, J=8.1, 8.1, 4.4 Hz, 1H);

¹³C NMR (125.7 MHz, CDCl₃): d=21.8 (CH₃), 34.6 (CH₂), 52.0 (CH₃),

54.8 (CH), 57.4 (CH₃), 57.9 (CH₃), 59.1 (CH₃), 69.6 (CH₂), 81.2 (CH),

84.0 (CH), 91.0 (C), 169.7 (C), 171.4 ppm (C); IR (film): n˜ =2935,

1737 cm^ꢁ1; MS (ESI⁺): m/z (%): 313 (100) [M⁺+Na]; HRMS (ESI⁺):

m/z calcd for C₁₃H₂₂NaO₇: 313.1263 [M⁺+Na]; found: 313.1261; elemen-

tal analysis calcd (%) for C₁₃H₂₂O₇(290.31): C 53.78, H 7.64; found: C

53.61, H 7.72.

Method B and subsequent diazomethane esterification: A solution of 46

(17 mg, 0.065 mmol) in dry CH₂Cl₂(1.3 mL), containing (diacetoxyiodo)-

benzene (25 mg, 0.078 mmol) and iodine (17 mg, 0.065 mmol) was irradi-

ated with a 80 W tungsten-filament lamp at room temperature under ni-

trogen for 2.5 h. The mixture was then poured into water and extracted

with CH₂Cl₂. The organic layer was washed with aqueous sodium thiosul-

fate, dried, and concentrated under reduced pressure. The residue was es-

terified with a solution of diazomethane in Et₂O at 08C. The solvent was

eliminated and the residue purified by silica gel column chromatography

(hexanes/EtOAc 8:2) to give 80 (13 mg, 0.045 mmol, 69%). Esterification

of the pure acid 79 (15.2 mg, 0.058 mmol) with an excess of diazomethane

in Et₂O at 08C afforded 80 (9.7 mg, 0.033 mmol, 58%).

Methyl (1S,2R,3S,4R,5S)-2-acetyloxy-3,4,5-tris(benzyloxy)-2-(tert-butyldi-

phenylsilyloxymethyl)cyclopentano-1-carboxylate (78): H₅IO₆(15 mg,

0.067 mmol) was added to a solution of 26 (25 mg, 0.034 mmol) in

MeOH (2.0 mL). The mixture was stirred for 3 h at room temperature

and concentrated under reduced pressure. A solution of the residue in

Et₂O (0.8 mL) was treated with diazomethane at 08C. The mixture was

then concentrated under reduced pressure and the residue purified by

silica gel column chromatography (hexanes/EtOAc 90:10) to give 78

(11 mg, 0.014 mmol, 42%) as a colorless oil: [a]_D= +17 cm³g^ꢁ1dm^ꢁ1(c=

0.40 in CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=1.03 (s, 9H), 1.88 (s,

3H), 3.610 (s, 3H), 3.611 (d, J=8.8 Hz, 1H), 3.93 (d, J=10.1 Hz, 1H),

4.13 (dd, J=7.1, 7.1 Hz, 1H), 4.23 (d, J=9.8 Hz, 1H), 4.39 (d, J=7.3 Hz,

1H), 4.52 (dd, J=8.8, 6.9 Hz, 1H), 4.62 (d, J=11.7 Hz, 1H), 4.65 (d, J=

12.0 Hz, 1H), 4.67 (d, J=12.3 Hz, 1H), 4.693 (d, J=11.0 Hz, 1H), 4.696

Methyl

(1S,2R,3S,5R)-2-acetyloxy-3-[(tert-butyldiphenylsilyl)oxy]-2-

[(tert-butyl diphenylsilyl)oxy]methyl-5-methoxycyclopentane-1-carboxy-

late (82): Method B: A solution of 47 (15.9 mg, 0.022 mmol) in dry

CH₂Cl₂

(0.5 mL),

containing

(diacetoxyiodo)benzene

(8.7 mg,

0.027 mmol) and iodine (5.7 mg, 0.022 mmol) was irradiated with a 80 W

tungsten-filament lamp at room temperature under nitrogen for 2 h. Sa-

turated aqueous sodium thiosulfate was then added until complete decol-

Chem. Eur. J. 2013, 00, 0 – 0

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www.chemeurj.org

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E. I. Leon, E. Suꢄrez et al.

orization of the iodine and the solvent was then evaporated at reduced

pressure. The residue was purified by silica gel column chromatography

(hexanes/EtOAc 1:1) to give acid 81 (13.0 mg, 0.019 mmol, 82%) as a

colorless oil. [a]_D=ꢁ9 cm³g^ꢁ1dm^ꢁ1(c=0.75 in CHCl₃); ¹H NMR

(500 MHz, CDCl₃): d=0.75 (s, 9H), 1.07 (s, 9H), 1.47 (ddd, J=12.9, 8.5,

8.5 Hz, 1H), 1.83 (s, 3H), 2.09 (ddd, J=13.3, 6.9, 6.9 Hz, 1H), 3.23 (d,

J=7.9 Hz, 1H), 3.31 (s, 3H), 3.92 (d, J=11.7 Hz, 1H), 4.29 (ddd, J=8.2,

8.2, 6.9 Hz, 1H), 4.33 (d, J=11.4 Hz, 1H), 4.65 (dd, J=8.2, 6.6 Hz, 1H),

7.19–7.64 ppm (m, 20H); ¹³C NMR (125.7 MHz, CDCl₃): d=18.9 (C),

19.2 (C), 21.4 (CH₃), 26.7 (3ꢆCH₃), 26.8 (3ꢆCH₃), 38.4 (CH₂), 57.8

(CH₃), 58.8 (CH), 69.2 (CH₂), 75.5 (CH), 78.9 (CH), 89.00 (C), 127.6–

135.8 (20ꢆCH), 131.05 (C), 131.2 (C), 132.5 (C), 133.1 (C), 169.0 (C),

169.7 ppm (C); IR (film): n˜ =2936, 1770, 1742 cm^ꢁ1; MS (ESI⁺): m/z

(%): 747 (100) [M⁺+Na]; HRMS (ESI⁺): m/z calcd for C₄₂H₅₂NaO₇Si₂:

747.3149 [M⁺+Na]; found: 747.3171; elemental analysis calcd (%) for

C₄₂H₅₂O₇Si₂(725.03): C 69.58, H 7.23; found: C 69.58, H 7.24.

(CH), 85.4 (C), 86.9 (CH), 127.67 (3ꢆCH), 127.71 (CH), 127.9 (3ꢆCH),

128.1 (2ꢆCH), 128.2 (2ꢆCH), 128.3 (2ꢆCH), 128.37 (2ꢆCH), 128.39

(2ꢆCH), 128.6 (CH), 128.8 (2ꢆCH), 135.7 (C), 137.7 (C), 138.0 (C),

138.3 (C), 169.3 (C), 169.9 ppm (C); IR (film): n˜ =2928, 1742, 1731 cm^ꢁ1

;

MS (ESI⁺): m/z (%): 633 (100) [M⁺+Na]; HRMS (ESI⁺): m/z calcd for

C₃₇H₃₈NaO₈: 633.2464 [M⁺+Na]; found: 633.2463; elemental analysis

calcd (%) for C₃₇H₃₈O₈(610.69): C 72.77, H 6.27; found: C 72.68, H 6.27.

(4aR,5S,6S,7R,7aS)-4a-(Acetyloxy)-6,7-dimethoxy-2,2-dimethylhexahy-

drocyclopenta[d]ACTHUNRGTNE[NUG 1,3]dioxine-5-carboxylic acid (84): A deoxygenated sol-

ution of diketone 22 (20.0 mg, 0.066 mmol) in dry C₆D₆(0.3 mL), was

placed in a resonance tube and irradiated with a daylight lamp at 36–

408C for 2.5 h. The mixture was concentrated under reduced pressure

and the residue dissolved in CH₂Cl₂(1.3 mL) and treated with (diacetox-

yiodo)benzene (24.6 mg, 0.076 mmol) and iodine (16.1 mg, 0.06 mmol).

The mixture was irradiated with an 80 W tungsten-filament lamp at room

temperature under nitrogen for 40 min. An excess of solid Na₂S₂O₃was

then added and the solvent concentrated under reduced pressure. The

residue was purified by silica gel column chromatography (hexanes/

EtOAc 8:2) to give 84 (17.4 mg, 0.054 mmol, 82%, from 22) as an amor-

phous solid. [a]_D=ꢁ19 cm³g^ꢁ1dm^ꢁ1(c=0.44 in CHCl₃); ¹H NMR

(400 MHz, CDCl₃): d=1.41 (s, 3H), 1.60 (s, 3H), 2.00 (s, 3H), 3.39 (s,

3H), 3.46 (s, 3H), 3.48 (d, J=3.2 Hz, 1H), 3.56 (d, J=9.3 Hz, 1H), 4.21

(d, J=11.9 Hz, 1H), 4.29 (ddd, J=9.3, 3.2, 1.1 Hz, 1H), 4.53 (d, J=

11.9 Hz, 1H), 4.79 ppm (d, J=1.0 Hz, 1H); ¹³C NMR (100.6 MHz,

CDCl₃): d=19.8 (CH₃), 21.6 (CH₃), 28.2 (CH₃), 52.1 (CH), 57.7 (CH₃),

58.2 (CH₃), 59.5 (CH₂), 73.8 (CH), 83.3 (C), 86.8 (CH), 89.9 (CH), 99.1

(C), 170.2 (C), 173.2 ppm (C); IR (CHCl₃, 0.2 mm): n˜ =3504, 3016, 1741,

1717 cm^ꢁ1; MS (ESI⁺): m/z (%): 341 (100) [M⁺+Na]; HRMS (ESI⁺):

m/z calcd for C₁₄H₂₂NaO₈: 341.1212 [M⁺+Na]; found: 341.1207; elemen-

tal analysis calcd (%) for C₁₄H₂₂O₈(318.32): C 52.82, H 6.97; found: C

52.86, H 6.92.

Method B and subsequent diazomethane esterification: A solution of 47

(19.0 mg, 0.027 mmol) in dry CH₂Cl₂(0.5 mL), containing (diacetoxyio-

do)benzene (10.4 mg, 0.032 mmol) and iodine (6.8 mg, 0.027 mmol) was

irradiated with a 80 W tungsten-filament lamp at room temperature

under nitrogen for 21 h. Saturated aqueous sodium thiosulfate was then

added until complete decolorization of the iodine and the solvent was

then evaporated at reduced pressure. The residue was esterified with a

solution of diazomethane in Et₂O at 08C. The solvent was eliminated and

the residue purified by silica gel column chromatography (hexanes/

EtOAc 9:1) to give 82 (11.9 mg, 0.016 mmol, 60%) as a colorless oil:

[a]_D= +7.6 cm³g^ꢁ1dm^ꢁ1(c=1.51 in CHCl₃);¹H NMR (500 MHz, CDCl₃):

d=0.92 (s, 9H), 1.10 (s, 9H), 1.63 (ddd, J=12.9, 8.2, 7.9 Hz, 1H), 1.81 (s,

3H), 2.09 (ddd, J=13.0, 7.2, 7.2 Hz, 1H), 3.26 (s, 3H), 3.48 (d, J=7.3 Hz,

1H), 3.56 (s, 3H), 4.10 (ddd, J=7.6, 7.6, 7.6 Hz, 1H), 4.18 (d, J=10.8 Hz,

1H), 4.27 (d, J=10.7 Hz, 1H), 4.71 (dd, J=7.9, 6.9 Hz, 1H), 7.26–7.44

(m, 12H), 7.54–7.58 (m, 4H), 7.70–7.71 ppm (m, 4H); ¹³C NMR

(100.6 MHz, CDCl₃): d=19.1 (C), 19.4 (C), 21.6 (CH₃), 26.9 (6ꢆCH₃),

37.8 (CH₂), 51.6 (CH₃), 54.0 (CH), 57.2 (CH₃), 65.0 (CH₂), 75.7 (CH),

80.0 (CH), 90.2 (C), 127.5 (2ꢆCH), 127.6 (6ꢆCH), 129.58 (CH), 129.62

(CH), 129.68 (CH), 129.72 (CH), 133.0 (C), 131.1 (C), 133.5 (C), 133.8

(C), 135.8 (2ꢆCH), 135.90 (2ꢆCH), 135.92 (2ꢆCH), 135.94 (2ꢆCH),

169.9 (C), 171.5 ppm (C); IR (film): n˜ =2933, 1737 cm^ꢁ1; MS (EI): m/z

(%): 681 (19) [M⁺ꢁtBu], 135 (100); HRMS (ESI⁺): m/z calcd for

C₄₃H₅₄NaO₇Si₂: 761.3306 [M⁺+Na]; found: 761.3325; elemental analysis

calcd (%) for C₄₃H₅₄O₇Si₂(739.06): C 69.88, H 7.36; found: C 70.07, H

7.42.

AHCTUNGTERG(NNUN 1S,2R,5R)-2-(Acetyloxy)-5-methoxy-2-[(tert-butyldiphenylsilyl)oxy]-

methyl-1-cyclopentanecarboxylic acid (85) from photocyclization-frag-

mentation of 42: A deoxygenated solution of 42 (40.8 mg, 0.090 mmol) in

dry C₆D₆(0.3 mL), was placed in a resonance tube and irradiated with a

daylight lamp at 36–408C for 5 h. The solution was heated to 608C for

2 h in the dark and concentrated under reduced pressure. The crude resi-

due in MeOH (3.0 mL), containing H₅IO₆(45.4 mg, 0.2 mmol), was stir-

red at room temperature for 3 h. The mixture was concentrated under re-

duced pressure and the residue purified by silica gel column chromatog-

raphy (hexanes/EtOAc 8:2!EtOAc) to give 85 (10.5 mg, 0.022 mmol,

46%) as an amorphous solid. [a]_D= +1 cm³g^ꢁ1dm^ꢁ1(c=0.52 in CHCl₃);

¹H NMR (400 MHz, CDCl₃): d=1.10 (s, 9H), 1.59 (m, 1H), 1.98 (s, 3H),

2.03–2.12 (m, 2H), 2.21 (m, 1H), 3.18 (d, J=6.3 Hz, 1H), 3.38 (s, 3H),

3.78 (d, J=10.4 Hz, 1H), 4.386 (d, J=10.4 Hz, 1H), 4.387 (ddd, J=6.3,

6.3, 6.3 Hz, 1H), 7.38–7.48 (m, 6H), 7.63–7.67 ppm (m, 4H); ¹³C NMR

(125.7 MHz, CDCl₃): d=19.2 (C), 21.8 (CH₃), 26.8 (3 ꢆ CH₃), 29.2

(CH₂), 32.1 (CH₂), 57.4 (CH₃), 59.0 (CH), 67.2 (CH₂), 82.5 (CH), 88.9

(C), 127.9 (2ꢆCH), 128.0 (2ꢆCH), 130.3 (2ꢆCH), 131.6 (C), 131.8 (C),

135.6 (2ꢆCH), 135.7 (2ꢆCH), 169.7 (C), 170.8 ppm (C); IR (CHCl₃,

0.2 mm): n˜ =2938, 1739 cm^ꢁ1; MS (ESI⁺): m/z (%): 493 (100) [M⁺+Na];

HRMS (ESI⁺): m/z calcd for C₂₆H₃₄NaO₆Si: 493.2022 [M⁺+Na]; found:

493.2021; elemental analysis calcd (%) for C₂₆H₃₄O₆Si (470.63): C 66.35,

H 7.28; found: C 66.12, H 7.03.

Method A and subsequent diazomethane esterification: A solution of 47

(40.7 mg, 0.057 mmol) in MeOH (3.4 mL) containing H₅IO₆(26.2 mg,

0.115 mmol) was stirred at room temperature for 20 h. The mixture was

concentrated under reduced pressure and the residue esterified with a

solution of diazomethane in Et₂O at 08C. The solvent was eliminated and

the residue purified by silica gel column chromatography (hexanes/

EtOAc 9:1) to give 81 (10.9 mg, 0.015 mmol, 26%). Esterification of

pure acid 81 (17.3 mg, 0.024 mmol) with an excess of diazomethane in

Et₂O at 08C afforded 82 (10.7 mg, 0.014 mmol, 60%).

(1S,2R,3S,4R,5S)-2-Acetyloxy-3,4,5-tris(benzyloxy)-2-(benzyloxymethyl)-

cyclopentanecarboxylic acid (83): A deoxygenated solution of 18 (80 mg,

0.135 mmol) in purified CDCl₃(2 mL), was placed in a resonance tube

and irradiated with a daylight lamp at 308C for 4 h. The mixture was con-

centrated under reduced pressure. The crude residue in EtOH (4 mL)

containing H₅IO₆(61 mg, 0.269 mmol) was stirred at room temperature

for 3 h. The mixture was concentrated under reduced pressure and the

residue purified by silica gel column chromatography (hexanes/EtOAc

9:1!1:1) to give 83 (48 mg, 0.079 mmol, 58% from 18) as an amorphous

solid: [a]_D= +11 cm³g^ꢁ1dm^ꢁ1(c=1.87 in CHCl₃); ¹H NMR (500 MHz,

CDCl₃): d=1.98 (s, 3H), 3.26 (d, J=9.1 Hz, 1H), 3.91 (dd, J=6.6, 6.6 Hz,

1H), 3.92 (d, J=10.7 Hz, 1H), 4.33 (d, J=10.7 Hz, 1H), 4.35 (d, J=

6.3 Hz, 1H), 4.61 (d, J=11.7 Hz, 2H), 4.63 (dd, J=9.1, 6.9 Hz, 1H), 4.66

(d, J=10.7 Hz, 2H), 4.67 (d, J=11.4 Hz, 1H), 4.68 (d, J=11.9 Hz, 1H),

4.73 (d, J=11.0 Hz, 1H), 4.87 (d, J=11.0 Hz, 1H), 7.27–7.37 ppm (m,

20H); ¹³C NMR (100.6 MHz, CDCl₃): d=21.6 (CH₃), 56.0 (CH), 71.6

(CH₂), 72.7 (CH₂), 73.6 (CH₂), 73.7 (CH₂), 74.3 (CH₂), 82.1 (CH), 85.2

Methyl (1S,2R,3S,4R,5S)-3,4,5-tris(benzyloxy)-2-(benzyloxy)methyl]cy-

clopentanecarboxylate (86): A solution of 83 (19 mg, 0.031 mmol) in

methanolic KOH (0.6 mL, 4 mg, 0.078 mmol) was stirred at room temper-

ature for 24 h. The mixture was neutralized with acid resin Dowex

50 Wꢆ8 (H⁺), filtered and concentrated under reduced pressure. A solu-

tion of the residue in Et₂O was treated with an excess of diazomethane

at 08C and concentrated under reduced pressure. The residue was puri-

fied by silica gel column chromatography (hexanes/EtOAc 8:2) to give 86

(18 mg, 0.031 mmol, 99%): colorless oil. [a]_D= +2 cm³g^ꢁ1dm^ꢁ1(c=0.25

1

in CHCl₃); H NMR (500 MHz, CDCl₃): d=3.11 (d, J=8.0 Hz, 1H), 3.64

(s, 3H), 3.69 (d, J=9.5 Hz, 1H), 3.75 (d, J=9.5 Hz, 1H), 3.89 (d, J=

3.7 Hz, 1H), 3.94 (dd, J=4.8, 4.0 Hz, 1H), 4.54 (m, 1H), 4.52–4.62 (m,

8H), 7.25–7.35 ppm (m, 20H); ¹³C NMR (125.7 MHz, CDCl₃): d=51.9

(CH₃), 54.0 (CH), 72.0 (CH₂), 72.30 (CH₂), 72.34 (CH₂), 72.8 (CH₂), 73.7

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Synthesis of Polyhydroxylated Cyclopentitols

FULL PAPER

(CH₂), 81.0 (C), 85.1 (CH), 86.6 (CH), 87.2 (CH), 127.6–128.3 (20ꢆCH),

137.9 (C), 138.05 (C), 138.09 (2ꢆC), 172.8 ppm (C); IR (film): n˜ =3499,

1732, 1068 cm^ꢁ1; MS (ESI⁺): m/z (%): 605 (100) [M⁺+Na]; HRMS

(ESI⁺): m/z calcd for C₃₆H₃₈NaO₇: 605.2515 [M⁺+Na]; found: 605.2513;

elemental analysis calcd (%) for C₃₆H₃₈O₇(582.68): C 74.21, H 6.57;

found: C 74.42, H 6.60.

J=2.6, 2.4 Hz, 1H), 4.37 (d, J=13.8 Hz, 1H), 4.45–4.71 (m, 8H), 4.63 (m,

1H), 4.69 (m, 1H), 4.83 (d, J=13.8 Hz, 1H), 7.26–7.36 ppm (m, 20H);

¹³C NMR (100.6 MHz, CDCl₃): d=51.6 (CH₃), 64.6 (CH₂), 71.8 (CH₂),

72.2 (CH₂), 72.6 (CH₂), 72.9 (CH₂), 85.8 (CH), 85.9 (CH), 87.8 (CH),

127.6–128.4 (20ꢆCH), 131.9 (C), 137.9 (C), 138.0 (C), 138.26 (C), 138.35

(C), 153.2 (C), 164.8 ppm (C); IR (film): n˜ =2922, 1722, 1070 cm^ꢁ1; MS

(ESI⁺): m/z (%): 587 (100) [M⁺+Na]; HRMS (ESI⁺): m/z calcd for

C₃₆H₃₆NaO₆: 587.2401 [M⁺+Na]; found: 587.2405; elemental analysis

calcd (%) for C₃₆H₃₆O₆(564.67): C 76.57, H 6.43; found: C 76.77, H 6.63.

(1S,2S,3R,4S,5R)-2,3,4-Tris(benzyloxy)-5-(benzyloxy)methyl-6-oxabi-

cycloACHTUNGTRENNUNG[3.2.0]heptan-7-one (87): A solution of 83 (15 mg, 0.025 mmol) in

methanolic KOH (0.5 mL, 4 mg, 0.071 mmol) was stirred at room temper-

ature for 24 h, neutralized with acid ion-exchange resin Dowex-50 Wꢆ8

(H⁺), filtered and concentrated under reduced pressure. Benzenesulfonyl

chloride (16 mL, 0.130 mmol) was added to a solution of the residue in

dry pyridine (0.1 mL) and the mixture stirred at 08C for 14 h. The solu-

tion was then poured into ice-water and extracted with Et₂O. The residue

was purified by silica gel column chromatography (hexanes/EtOAc 8:2)

to give 87 (10 mg, 0.018 mmol, 73%, two-step) as a colorless oil. [a]_D= +

2 cm³g^ꢁ1dm^ꢁ1(c=0.50 in CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=3.97

Acknowledgements

This work was supported by the Investigation Programs (CTQ2010-

18244) of the Ministerio de Economꢂa

(SolSub20081000192) of the Gobierno de Canarias. D.A.-D. thanks the

Ministerio de Economꢂa Competitividad for fellowship. C.R.-F.

y

Competitividad and

(d, J=12.0 Hz, 1H), 3.99 (d, J=11.7 Hz, 1H), 4.00 (dd, J=1.5 Hz, J_W

=

y

a

1.4 Hz, 1H), 4.16 (ddd, J=2.4, 2.0 Hz, J_W=1.4 Hz, 1H), 4.19 (d, J=

4.7 Hz, 1H), 4.22 (dd, J=1.9, 1.9 Hz, 1H), 4.47 (d, J=12.0 Hz, 1H), 4.48

(d, J=12.0 Hz, 1H), 4.52 (d, J=11.7 Hz, 1H), 4.52 (d, J=12.0 Hz, 1H),

4.53 (d, J=12.3 Hz, 1H), 4.57 (d, J=12.0 Hz, 1H), 4.60 (d, J=12.3 Hz,

1H), 4.63 (d, J=12.0 Hz, 1H), 7.22–7.36 ppm (m, 20H); ¹³C NMR

(100.6 MHz, CDCl₃): d=60.5 (CH), 67.6 (CH₂), 71.1 (CH₂), 72.1 (CH₂),

73.0 (CH₂), 73.8 (CH₂), 81.4 (CH), 82.9 (CH), 86.8 (CH), 88.1 (C), 127.6–

128.5 (20ꢆCH), 137.2 (C), 137.29 (C), 137.34 (C), 137.4 (C), 167.1 ppm

(C); IR (film): n˜ =2918, 1828, 1087 cm^ꢁ1; MS (ESI⁺): m/z (%): 573 (100)

[M⁺+Na]; HRMS (ESI⁺): m/z calcd for C₃₅H₃₄NaO₆: 573.2253 [M⁺

+Na]; found: 573.2249; elemental analysis (%) for C₃₅H₃₄O₆(550.64): C

76.34, H 6.22; found: C 76.29, H 6.47.

thanks the Programa I3P-CSIC for a postdoctoral contract.

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(1R,2S,3R,4S,5S)-2,3,4-Tris(benzyloxy)-1-(benzyloxy)methyl-5-(hydroxy-

methyl)cyclopentanol (88): LiAlH₄(6 mg, 0.082 mmol) was added to a

solution of 83 (25 mg, 0.041 mmol) in dry THF (1.6 mL) and the suspen-

sion stirred at 08C under nitrogen for 4 h. A saturated solution of

Na₂SO₄was then added, the white solid mass precipitate was filtered

through Celite, and the solvent concentrated under reduced pressure.

The residue was purified by silica gel column chromatography (hexanes/

EtOAc 1:1!4:6) to give 88 (18 mg, 0.032 mmol, 78%) as a colorless oil:

1

[a]_D=ꢁ8.2 cm³g^ꢁ1dm^ꢁ1(c=0.11 in CHCl₃); H NMR (500 MHz, CDCl₃):

d=2.21 (ddd, J=9.3, 6.0, 3.7 Hz, 1H), 3.61 (d, J=9.5 Hz, 1H), 3.76 (d,

J=9.1 Hz, 1H), 3.79 (dd, J=11.6, 6.0 Hz, 1H), 3.83 (d, J=4.7 Hz, 1H),

3.87 (dd, J=11.6, 3.5 Hz, 1H), 3.91 (dd, J=5.4, 5.4 Hz, 1H), 4.09 (dd, J=

8.8, 5.4 Hz, 1H), 4.45–4.73 (m, 8H), 7.25–7.38 ppm (m, 20H); ¹H NMR

(500 MHz, C₆D₆): d=2.24 (brs, 1H), 2.31 (ddd, J=4.7, 4.7, 9.5 Hz, 1H),

3.08 (brs, 1H), 3.51 (d, J=9.5 Hz, 1H), 3.68 (d, J=9.5 Hz, 1H), 3.84 (br

t, J=4.4 Hz, 2H), 3.93 (d, J=5.4 Hz, 1H), 4.05 (dd, J=5.7, 5.7 Hz, 1H),

4.22 (s, 2H), 4.25 (dd, J=6.0, 8.5 Hz, 1H), 4.54 (d, J=12.0 Hz, 1H), 4.57

(d, J=11.0 Hz, 1H), 4.57 (d, J=11.0 Hz, 1H), 4.62 (d, J=11.7 Hz, 1H),

4.64 (d, J=11.5 Hz, 1H), 4.67 (d, J=11.7 Hz, 1H), 7.05–7.36 ppm (m,

20H); ¹³C NMR (100.6 MHz, CDCl₃): d=49.9 (CH), 60.5 (CH₂), 72.2

(CH₂), 72.6 (CH₂), 72.6 (CH₂), 73.1 (CH₂), 73.9 (CH₂), 80.6 (C), 82.7

(CH), 86.9 (CH), 87.8 (CH), 127.7–128.5 (20ꢆCH), 137.4 (C), 138.1 (C),

138.2 (C), 138.4 ppm (C); ¹³C NMR (125.7 MHz, C₆D₆): d=50.0 (CH),

60.9 (CH₂), 72.2 (CH₂), 72.6 (CH₂), 72.8 (CH₂), 73.6 (CH₂), 73.7 (CH₂),

80.7 (C), 82.8 (CH), 87.7 (CH), 88.6 (CH), 127.6–128.6 (20ꢆCH), 138.3

(C), 139.0 (C), 139.2 (C), 139.3 ppm (C); IR (film): n˜ =3445, 2918,

1075 cm^ꢁ1; MS (ESI): m/z (%): 577 (100) [M⁺+Na]; HRMS (ESI⁺): m/z

calcd for C₃₅H₃₈NaO₆: 577.2566 [M⁺+Na]; found: 577.2564; elemental

analysis calcd (%) for C₃₅H₃₈O₆(554.67): C 73.79, H 6.91; found: C 73.39,

H 7.31.

Methyl (3R,4S,5S)-3,4,5-tris(benzyloxy)-2-(benzyloxy)methyl-1-cyclopen-

tene-1-carboxylate (89): Tf₂O (14 mL, 0.081 mmol) was added dropwise to

a solution of 86 (16 mg, 0.027 mmol) in dry CH₂Cl₂containing dry pyri-

dine (14 mL) at 08C. The mixture was stirred at room temperature for

24 h, and concentrated under reduced pressure. The residue was purified

by silica gel column chromatography (hexanes/EtOAc 8:2) to give 89

(14 mg, 0.025 mmol, 93%) as a colorless oil. [a]_D=ꢁ16 cm³g^ꢁ1dm^ꢁ1(c=

1.06 in CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=3.72 (s, 3H), 4.05 (dd,

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Chem. Eur. J. 2013, 00, 0 – 0

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Synthesis of Polyhydroxylated Cyclopentitols

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Sequential Norrish type II photoelimination and intramolecular aldol cyclization of α-diketones: Synthesis of polyhydroxylated cyclopentitols by ring contraction of hexopyranose carbohydrate derivatives

DOI: 10.1002/chem.201301230

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