D-Fructose- and L-sorbose-derived endo- and exo-hydroxyglycal esters and some of their chemistry

Article abstract of DOI:10.1016/j.tetasy.2004.07.018

Dehydrobrominations of benzoylated β-d-fructopyranosyl and α-l-sorbo-pyranosyl bromides have been examined to obtain suitable conditions for effecting the elimination toward the exo- as well as the endo-positions. In the fructose case, exposure to DBU in

Full text of DOI:10.1016/j.tetasy.2004.07.018

0
Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 2693–2701
D-Fructose- and L-sorbose-derived endo- and
exo-hydroxyglycal esters and some of their chemistryq
Andrea Boettcher and Frieder W. Lichtenthaler*
Clemens-Scho¨pf-Institut fu¨r Organische Chemie und Biochemie, Technische Universita¨t Darmstadt, Petersenstraße 22,
D-64287 Darmstadt, Germany
Received 26 June 2004; accepted 12 July 2004
Dedicated to Professor Karsten Krohn on the occasion of his 60th birthday
Abstract—Dehydrobrominations of benzoylated b-D-fructopyranosyl and a-L-sorbo-pyranosyl bromides have been examined to
obtain suitable conditions for effecting the elimination toward the exo- as well as the endo-positions. In the fructose case, exposure
to DBU in acetonitrile generates the exo-hydroxyfructal ester (81%) while refluxing in xylene gives the endo analog (53%). In the L-
sorbose case, the regioselectivities are the inverse. Simple reactions of exo- and endo-products provide a series of highly versatile
enantiopure six-carbon building blocks, together with a crystalline derivative of the fungal metabolite microthecin.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
elaborates the 2-ketohexosyl bromide 4,8 a most useful
glycosyl donor for the indirect generation of b-D-man-
nosidic linkages, since its glycosidation exclusively yields
b-D-glycosiduloses8,9 while the subsequent hydride
reduction can be performed in an essentially manno-
specific manner.9 This preparatively expedient sequence
1 ! 4 ! 5 constitutes as the essence of the ꢀulosyl donor
approachꢁ to b-D-mannosides,6c,10–13 which has been
carried to the hexasaccharide level14 and also applied
to the acquisition of C-glycosides.15 Treatment with
hydroxylamine in pyridine exclusively cleaves the enol
ester linkage to provide oxime 6,16 opening up, via
deoximation, a simple access to 1,5-anhydro-D-fructose
tribenzoate 7, and, through acetate-induced b-elimina-
tion of benzoic acid, to dihydropyranone 816––a most
useful enantiopure building block, as it has enabled
straightforward syntheses of the marine natural
products (S,S)-palythazin17 and (S,S)-bissetone.18 Of
similar preparative versatility are the readily accessible
six-carbon synthons 9,19 10 (this paper), and 11,20 in
which a useful functionality on one side of the pyranoid
ring is paired with chirality on the other, so that
addition reactions proceed with high stereo-
selectivity.6b,21
2-Hydroxyglycal esters, first encountered by Maurer and
Mahn in 1927,2 have become exceedingly well accessible
as the three steps required from a basic sugar––acyl-
ation, anomeric halogenation, and amine-promoted
dehydrohalogenation––can be combined into a continu-
ous one-pot operation allowing overall yields in the 70–
80% range.3,4 Their basic chemistry has already been
reviewed 50years ago,5 yet the vast potential toward the
generation of enantiomerically pure five- or six-carbon
building blocks has only been exploited within the last
20years.1,6 These recent developments are illustrated in
Scheme 1 with the ensuing reactions of the D-glucose-de-
rived perbenzoyl-1-deoxy-D-arabino-hex-1-enitol 1: BF3-
catalyzed peracid oxidation effectively elicits conversion
into enol lactone 2,7 due to elimination of the allylic ben-
zoyloxy group, the seizure of the pyranoid allyloxonium
ion by the peracid at the anomeric carbon, and the frag-
mentation of the perester. Acid-induced addition of an
alcohol smoothly affords 2,3-unsaturated glycosides,
for example, 3.3b Exposure to NBS/methanol efficiently
q Part 33 of the series ꢀSugar-Derived Building Blocksꢁ. For Part 32, see
Ref. 1.
In view of the wealth of synthetic uses that have been
found for D-glucose-based hydroxyglycal esters of type
1, it is somewhat surprising that not more attention
*
Corresponding author. Fax: +49 6151 166674; e-mail: lichtenthaler@
chemie.tu-darmstadt.de
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.07.018

2694
A. Boettcher, F. W. Lichtenthaler / Tetrahedron: Asymmetry 15 (2004) 2693–2701
BzO
OBz
OBz
MeO
O
OBz
3
OBz
OBz
OBz
OBz
BzO
O
O
b
O
2
Br
O
a
d
4
c
OBz
OBz
OBz
OBz
OBz
OBz
OBz
OBz
BzO
X
HO
e
OBz
O
O
1
O
iP2Gal
O
5
6 X = NOH
7 X = O
f
i
g
OBz
h
O
O
OBz
OBz
OBz
O
RO
O
O
10 R = Bz
11 R = iPr
8
OBz
BzO
O
9
Scheme 1. Reagents and yields: (a) 3-ClC6H4CO3H, BF3, 91%;7 (b) MeOH, BF3, 72%;3b (c) NBS, MeOH, 89%;8 (d) iP2Gal, Ag2CO3, then L-
selectride, 79%;9 (e) NH2OH, pyridine, 93%;16 (f) CH3CHO, HCl, 88%;16 (g) NaOAc, acetone, 92%;16 (h) Cl2 in toluene, À30ꢁC, then aq NaHCO3,
65%;19 (i) 10: BF3ÆOEt2, CH2Cl2, 62% (see Experimental); 11: iPrOH, SnCl4, 42%.20
has been paid to the analogs derived from well-accessi-
ble ketoses such as D-fructose and L-sorbose. The rea-
sons undoubtedly lie in their hitherto insufficient
preparative accessibility. L-Sorbose-derived endo-3-
hydroxyglycals have been encountered as side products
in the synthesis of L-sorbosyl-nucleosides,22–24 acetyl-
ated exo-analogs on thermolysis of D-fructose and L-sor-
bose peracetates in yields of 1–15%.25 As a consequence,
we herein report the development of viable procedures
for the acquisition of D-fructose-derived exo- 13 and
endo-hydroxyglycal esters 14, their preparatively ade-
quate generation and the first evaluation of their
chemistry.
which correlate well with the data found for the respec-
tive acetylated analog previously obtained in low yield
on thermolysis of fructopyranose pentaacetate, whilst
corresponding signals for the E-isomer appeared at dis-
tinctly lower field.25 Thus, the base-induced elimination
of HBr in 12 exclusively occurs from a conformation in
which O-1 and the ring oxygen are in a gauche disposi-
tion, utilizing the exocyclic hydrogen anti to the bromine
rather than the neighboring, equally anti-disposed ring
proton (Scheme 2).
OH
Br
OBz
H
OH
1. BzCl
2. HBr
O
O
OBz
OH
H1
OH
D
OBz
2. Results and discussion
H3
12
HO
BzO
-Fructose
2.1. exo- and endo-3-Hydroxyfructal esters
1. NaI/acetone
2. ∆ (xylene, 140oC)
53%
81% DBU/MeCN
Dehydrohalogenation of benzobromofructose 12,
readily prepared from the parent ketose in a two-step
one-pot procedure,26 may proceed either toward the
exo- or endo-product, depending on whether abstraction
of an exocyclic or a pyranoid ring hydrogen is involved.
Thus, conditions had to be found that steer the elimina-
tion exclusively or at least with high regioselectivity in
one or the other direction.
O
OBz
O
BzO
OBz
BzO
BzO
OBz
OBz
OBz
13
14
Scheme 2. Preparation of exo- and endo-hydroxyfructal esters.
Exposure of 12 to DBU in acetonitrile at ambient tem-
perature smoothly effected the elaboration of a single
product, isolable in 81% yield, which proved to be the
Z-exo-hydroxyfructal ester 13. The Z-configuration at
its double bond followed from the comparatively high
field signals for C-1 and C-2 (136.0 and 123.8ppm),
As the amine-induced dehydrobromination of 12 exclu-
sively elaborated the exo-product, the generation of the
endo-hydroxyfructal ester 14 required basically different
conditions. Refluxing of 12 or the respective chloride27
with mercuric cyanide in benzene24 or xylene (140ꢁC)

A. Boettcher, F. W. Lichtenthaler / Tetrahedron: Asymmetry 15 (2004) 2693–2701
2695
OBz
OBz
OBz
OBz
OBz
OBz
BzO
BzO
EtOH
75%
NH2OH
73%
HON
O
O
O
OEt
RON
13
15 R = H
17
16 R = Bz
MeCHO/H+
76%
OBz
OBz
OBz
OBz
OBz
OBz
CH2PPh3
65%
EtOH
78%
EtO
O
O
O
O
OEt
18
19
20
Scheme 3. Versatile enantiopure six-carbon building blocks from exo-hydroxyfructal ester 13.
OBz
invariably resulted in 1:1 to 2:1 mixtures of endo- 14 and
exo- 13 products (1H NMR), from which the former
could be isolated in yields of up to 35% only. After
extensive experimentation, optimum conditions were
found in refluxing the respective iodide, generated in situ
from bromide 12, for 4h in xylene, that is, without
Hg(CN)2. The 5:1 endo/exo mixture (1H NMR) thus
obtained allowed the isolation of the endo-product,
dihydropyran 14, in 53% yield.
OBz
BzO
BzO
OBz
BzO
BzO
MeOH/BF3
74%
O
O
MeO
14
MeOH
SnCl4
21
MeOH
SnCl4
-10˚C
88%
72%
r.t.
O
With the exo- and endo-hydroxyfructal esters 13 and 14
now in hand on a preparative scale––their obtention
from D-fructose requires three large scale-adaptable
steps feasible in 57% and 45% overall yield, respectively,
their chemistry could be studied.
BzO
BzO
O
O
MeO
O
24
22 R = Bz
23 R = H
H+
As enol ester cleavage in aldose-derived hydroxyglycal
esters can selectively be effected by hydroxylaminolysis
thus capturing the ketone liberated as its oxime,16 the
exo-hydroxyfructal ester 13 was expected to provide
the respective aldoxime. The reaction, however, went
further since the initially generated aldehyde, under
the slightly basic conditions, eliminated benzoic acid
prior to oximation to give the enal-oxime 15 (73%).
The underlying enal could readily be liberated by trans-
oximation with an acetaldehyde (15 ! 19), and could be
olefinated via a standard Wittig methodology (19 ! 20).
The enal-oxime 15 as well as the free enal readily under-
went addition of alcohols, with traces of acid in chloro-
form already being sufficient enough to generate either a
glycoside (15 ! 17) or the acetal of 2-formyldihydropy-
ran (19 ! 18) (Scheme 3).
O
O
HO
O
O
O
O
HO
26
25
microthecin
Scheme 4. Products derived from benzoylated endo-hydroxyfructal.
formation of 21 was followed by another elimination of
benzoic acid to give the well-crystallizing dihydropyra-
none 24––not only a uniquely functionalized six–carbon
building block, but de facto the first enantiopure, crys-
talline derivative of microthecin 26, a fungal metabolite,
which, due to its free anomeric center, is isolable from
natural sources28 in its racemic form only (Scheme 4).
The basic ensuing reactions of endo-hydroxyfructal ester
14 are expectedly different. When exposed at ambient
temperature to methanol in CH2Cl2 in the presence of
BF3-etherate, addition to the pro-anomeric carbon of
the double bond occurs stereoselectively from the side
opposite to the two chiral benzoyloxy substituents, elab-
orating through concomitant b-elimination, dihydropy-
ran 21 (74%). Performing the addition with a stronger
Lewis acid such as SnCl4, the outcome depended on
the conditions: at room temperature, a pyran ! furan
skeletal rearrangement was elicited to provide benzoyl-
oxyacetyl-furan 22 (88%), whereas at À10ꢁC, the initial
When subjected to SnCl4 in CHCl2 in the presence of
methanol, or on brief heating in aqueous solution with
a strongly acidic ion exchanger, 21 as well as 24 elabo-
rated the benzoyloxymethyl-furyl-ketone 22––as did
the previously prepared,29 albeit syrupy, microthecin
derivative 25 on the attempt to remove the isopropylid-
ene group by acid treatment (25 ! 23).
Attempts to subject 14 to hydroxylaminolysis for libera-
tion of the C-3 carbonyl as its oxime were not successful,
as the enol ester linkage proved to be stable toward

2696
A. Boettcher, F. W. Lichtenthaler / Tetrahedron: Asymmetry 15 (2004) 2693–2701
standard conditions (NH2OH/pyridine, rt), even after
prolonged exposure (7days), whereas at 50ꢁC, complex
product mixtures were formed, seemingly due to enol
ester cleavage and subsequent elimination of benzoic
acid.
ogous course involving hydride addition and subsequent
elimination to deliver the dihydropyran-building block
31 in a crystalline form. When using stronger Lewis
acids such as SnCl4 in CH2Cl2 in the presence of an
alcohol, or on brief heating with a strongly acidic ion
exchanger, ring contraction to the 2-(benzoyloxy-
acetyl)furan 22 prevailed.
2.2. endo-3-Hydroxysorbal
With L-sorbose being the 5-epimer of D-fructose, it was
anticipated that the conditions elaborated for the regio-
selective dehydrobromination of 12 toward the exo- or
endo-hydroxyfructal esters could also be applied to the
tetrabenzoyl-a-L-sorbopyranosyl bromide 27. Surpris-
ingly though, on in situ generation of the iodide by
exposure to NaI in acetone and subsequent addition of
DBU, the direction of the elimination was in favor of
the endo-product 28––obviously due to the fact that
the equatorially disposed 5-OBz in 27 exerts no steric
shielding on H-3 (as is the case in the fructose analog
12 with its axially oriented 5-OBz), thereby minimizing
the difference in the ease of abstraction of H-1 and
H-3 by base. Accordingly, mixtures of endo-28 and
exo-29 isomers are obtained, which are not appreciably
separable by chromatography due to nearly identical Rf
values. Most favorable conditions found for acquiring a
high proportion of the endo-hydroxysorbal ester 28
comprised in situ generation of the sorbosyl iodide fol-
lowed by DBU-promoted dehydrohalogenation. The
resulting 5:1 mixture of 28 and 29 (1H NMR) was sub-
jected to hydroxylaminolysis, which converted the exo-
isomer into ene-oxime 32, yet––in analogy to 14––left
the endo-isomer untouched. In this way, 28 was obtained
in its pure form with a yield of 54% (based on 27)
(Scheme 5).
3. Conclusion
In summary, practical protocols have been developed
for the dehydrohalogenation of perbenzoylated b-D-
fructopyranosyl bromide 12. A strong base (DBU in
acetonitrile) caused a 1,2-elimination to give the exo-
hydroxyfructal ester 13 (81%), while refluxing in xylene
resulted in the preferential 3,2-excision toward the
endo-product 14 (53%). The axially disposed 5-OBz in
12 was seen to impose a distinct control over the regio-
selectivity of the elimination by shielding H-3 from
abstraction by base. With a-L-sorbosyl bromide 27,
bearing the 5-OBz in an equatorial orientation, base
treatment preferentially utilizes the unshielded H-3 for
halide elimination to give the endo-hydroxysorbal ester
28 (54%).
In analogy to the aldose-derived 2-hydroxyglycal esters,
which have served as starting materials for a plethora
of enantiopure building blocks (cf. Scheme 1),5,6 the
ketose-derived endo- and exo-hydroxyglycals described
herein give a rich ensuing chemistry, as simple reactions
providing a set of highly versatile enantiopure six-car-
bon synthons. One has already been utilized to prepare
a
microthecin.
crystalline derivative of the fungal metabolite
The reactions of 28 paralleled those of the fructal ana-
log, for example, BF3-promoted addition of methanol
preferentially occurred from the side opposite to the
5-OBz group and was followed by the elimination of
the allylic 4-OBz to provide the (2R,5S)-dihydropyran
30, the enantiomer of fructose-derived 21. Exposure to
triethylsilane in the presence of BF3-etherate––condi-
tions that have successfully been used for the allylic
deoxygenation of glycals30––resulted in a sterically anal-
4. Experimental
4.1. General methods
Melting points were determined with a Bock hot-stage
microscope and are uncorrected. Optical rotations were
measured on a Perkin–Elmer 241 polarimeter at 20ꢁC
OBz
OBz
Br
OBz
1. NaI
acetone
OBz
OBz
BzO
BzO
BzO
BzO
H
O
BzO
+
OBz
1
2. DBU
H
BzO
O
O
H3
29
28
27
MeOH/BF3
Et3SiH
BF3
NH2OH
OBz
O
OBz
OBz
BzO
BzO
OBz
BzO
MeO
BzO
O
O
RON
30
32 R = H
33 R = Bz
31
Scheme 5. L-Sorbose-derived endo-hydroxyglycal esters and ensuing products.

A. Boettcher, F. W. Lichtenthaler / Tetrahedron: Asymmetry 15 (2004) 2693–2701
2697
using a cell of 1m path length; concentration (c) in
g/100mL and solvent are given in parentheses. 1H
and 13C NMR spectra were recorded on a Bruker
ARX-300 or a Bruker Avance 500 spectrometer in
CDCl3. Mass spectra were acquired on Varian MAT
311 and MAT 212 spectrometers. Microanalyses were
determined on a Perkin–Elmer 240 elemental analyzer.
Analytical thin layer chromatography (TLC) was per-
formed on precoated Merck plastic sheets (0.2mm silica
gel 60 F254) with detection by UV (254nm) and/or spray-
ing with H2SO4 (50%) and heating. Column and flash
chromatography was carried out on Fluka silica gel 60
(70–230 mesh) using the specified eluants.
EtOAc. Evaporation of the eluate to dryness yielded
20
7.15g (81%) of 13 as a colorless foam; ½aŠ ¼ À48:6
D
(c 1.0, CHCl3). 1H NMR (300MHz, CDCl3): d 4.36
(dd, 1H, H-6a), 4.40 (dd, 1H, H-6b), 5.84 (dd, 1H,
H-4), 5.94 (ddd, 1H, H-5), 6.14 (dd, 1H, H-3), 7.34 (d,
1H, H-1), 7.24–8.12 (m, 20H, 4C6H5); J1,3 = 0.7,
J3,4 = 6.7, J4,5 = 3.1, J5,6 = 4.2 and 6.2, J6,6 = 11.5Hz.
13C NMR (75.5MHz, CDCl3): d 67.0 (C-6), 67.3
(C-3), 67.4 (C-5), 69.7 (C-4), 123.8 (C-1), 128.5–
133.7 (C6H5), 136.0 (C-2), 162.9, 164.9, 165.2, 165.4
(4BzCO). MS (FD) m/z 578 (M+ÀBz). Anal. Calcd for
C34H26O9 (578.6): C, 70.58; H, 4.53. Found: C, 70.48;
H, 4.50.
Essential for the success is the use of an acetic acid-free
bromide 12, prepared by treatment of tetra-O-benzoyl-
b-D-fructopyranose with HBr in CH2Cl2.26 When gener-
ating 12 by exposure to HBr in acetic acid, it contains
0.25–0.3molequiv of acetic acid.32
4.2. (2R,6S)-2-Benzoyloxy-6-(benzoyloxymethyl)-2H-
pyran-3(6H)-one 10
BF3-etherate (0.24mL, 1.9mmol) was added dropwise
to a stirred solution of tetra-O-benzoyl-D-arabino-hex-
1-enitol 13 in CH2Cl2 (1.00g, 1.72mmol in 50mL), and
stirring at ambient temperature was continued for a
total of 3days with another BF3ÆEt2O portion
(0.24mL) having been added after 24h. The brownish
mixture was then poured into 50mL of satd NaHCO3
solution, followed, after stirring for 1h, by separation
of the organic layer, and repeated extraction of the
aqueous phase with CH2Cl2. Washing of the combined
CH2Cl2 extracts with HCl and water (2 · 25mL each),
drying over Na2SO4, and removal of the solvent in va-
cuo left a syrup, which was purified by elution from a sil-
ica gel column (2.5 · 30cm) with 20:1 toluene/EtOAc.
The major fraction contained 10 (Rf 0.33, toluene/
EtOAc, 10:1), which was isolated by evaporation to dry-
4.4. (3R,4R)-3,4,5-Tri(benzoyloxy)-6-benzoyloxymethyl-
3,4-dihydro-2H-pyran 14
To a stirred solution of fructosyl bromide 1226 (2.0g,
˚
3.0mmol) and freshly desiccated molecular sieves (4A)
in anhydrous acetone (50mL), sodium iodide (0.7g,
4.7mmol) was added and the mixture kept at ambient
temperature for 10h. The resulting suspension was fil-
tered through a layer of silica gel, followed by the re-
moval of the solvent in vacuo at a bath temperature
not exceeding 25ꢁC. The syrup thus obtained was taken
up in boiling xylene (50mL) and the solution stirred at
140ꢁC for 1.5h. The mixture was then allowed to return
to room temperature, whereafter water (20mL) was
added (to hydrolyze residual fructosyl iodide), followed
by filtration of the brown solution through a layer of sil-
ica gel, and removal of the solvent in vacuo. The result-
ing residue was dissolved in CHCl3 (50mL) and the
solution successively washed with water, NaHCO3 solu-
tion, and again with water (25mL each). Drying over
MgSO4, and concentration in vacuo gave a syrup con-
sisting of 13 (Rf 0.28, TLC in 10:1 toluene/EtOAc), 14
(major, Rf 0.20), and fructose tetrabenzoate (12, OH in-
stead of Br; Rf 0.12). Separation was effected on a silica
gel column (4 · 40cm) by elution with 10:1 toluene/
EtOAc. Removal of the solvents from the fraction
eluted first afforded 183mg (11%) of exo-olefin 13 as a
uniform foam.
ness, the solid residue crystallizing on trituration with
20
ether: 0.37g (62%); mp 96–97ꢁC; ½aŠ ¼ À168:8 (c 1,
D
CHCl3).31 1H NMR (500MHz, CDCl3): d 4.51 and
4.67 (two 1H-dd, CH2), 5.04 (oct, 1H, H-6), 6.41 (ddd,
1H, H-4), 6.48 (s, 1H, H-2), 7.23 (dd, 1H, H-5), 7.4–
8.1 (m, 10H, 2C6H5); J2,4 = 0.5, J4,5 = 10.7, J4,6 = 2.5,
J5,6 = 1.7, J6,CH = 4.8, JCH = 11.7Hz. 13C NMR
2
2
(75.5MHz, CDCl3): d 64.7 (CH2), 68.5 (C-6), 90.0 (C-
2), 126.7 (C-4), 128.5–133.9 (C6H5), 147.5 (C-5), 164.6
and 166.1 (BzCO), 186.7 (C-3); MS (FI) m/z 352 (M+).
Anal. Calcd for C20H16O6 (352.34): C, 68.18; H, 4.58.
Found: C, 68.10; H, 4.53.
4.3. 1,3,4,5-Tetra-O-benzoyl-2,6-anhydro-D-arabino-hex-
1-(Z)-enitol 13
Evaporation of the next major fraction eluted (Rf 0.20),
yielded 0.93g (53%) of endo-hydroxyfructal ester 14 as
To a stirred solution of 10.0g (15.2mmol) of 1,3,4,5-
tetra-O-benzoyl-b-D-fructopyranosyl bromide 1226 and
20
D
1
an amorphous powder; ½aŠ ¼ þ7:1 (c 2.7, CHCl3). H
˚
freshly desiccated molecular sieves (4A) in anhydrous
NMR (300MHz, CDCl3): d 4.35 (dd, 1H, H-2a),
4.43 (dd, 1H, H-2b), 4.96, 5.00 (two 1Hd, CH2OBz),
5.80 (ddd, 1H, H-3), 6.33 (dd, 1H, H-4), 7.25–8.05
(m, 20H, 4C6H5); J2,2 = 10.8, J2,3 = 3.8 and 9.1, J2,
acetonitrile (100mL), DBU (3.4mL, 22.7mmol) was
added dropwise and with care over the course of
30min, and stirring then continued for 1.5h. Concentra-
tion in vacuo of the resulting brown solution to about
one-third and subsequent dilution with CHCl3 (50mL)
were followed by washing with water, 2M HCl, satd
NaHCO3 solution, and water (2 · 50mL each). Drying
over MgSO4 and removal of the solvent in vacuo left a
yellowish syrup, which was purified by quick elution
from a silica gel column (3 · 30cm) with 10:1 toluene/
4 = 1.0,
J3,4 = 4.2,
JCH = 13.3Hz.
13C
NMR
2
(75.5MHz, CDCl3): d 59.0 (CH2OBz), 63.8 (C-2), 65.2
(C-4), 66.0 (C-3), 125.4 (C-5), 146.6 (C-6), 128.3–133.7
(C6H5), 165.1, 165.8, 166.0 (4BzCO). MS (FD) m/z
578 (M+À1), 457 (M+ÀHOBz). Anal. Calcd for
C34H26O9 (578.6): C, 70.58; H, 4.53. Found: C, 70.39;
H, 4.64.

2698
A. Boettcher, F. W. Lichtenthaler / Tetrahedron: Asymmetry 15 (2004) 2693–2701
The fraction eluted last contained 1,3,4,5-tetra-O-ben-
zoyl-b-D-fructopyranose (350mg, 19%), formed by the
hydrolysis of the unreacted in situ-generated fructosyl
iodide.
(4mL). Stirring at ambient temperature was continued
for 3days, whereafter TLC indicated absence of educt.
Concentration of the solution in vacuo left a syrup,
which was purified by elution from a silica gel column
(3 · 13cm) with 10:1 toluene/EtOAc to furnish, upon
evaporation of the eluant in vacuo, 17 (421mg, 75%)
4.5. (3S,4S)-Bis(benzoyloxy)-6-formyl-3,4-dihydro-2H-
pyran oxime 15
20
1
as a colorless foam; ½aŠ ¼ À152:8 (c 1.0, CHCl3). H
D
NMR (300MHz, CDCl3): d 1.24 (t, 3H, EtCH3), 2.35
(m, 2H, 3H2), 3.58 (two 1H-q, EtCH2), 4.07 (dd, 1H,
H-6a), 4.13 (dd, 1H, H-6b), 5.60 (m, 1H, H-5), 5.70
(m, 1H, H-4), 7.3–8.1 (m, 10H, 2C6H5), 7.47 (s, 1H,
CHN), 8.59 (s, 1H, NOH); J5,6 = 1.2 and 1.8,
J6,6 = 13.0Hz. MS (FD) m/z 413 (M+). Anal. Calcd for
C22H23NO7 (413.4): C, 63.91; H, 5.61; N, 3.39. Found:
C, 63.71; H, 5.46; N, 3.22.
Hydroxylamine hydrochloride (7.2g, 0.1mol) was added
to a solution of 7.5g (13mmol) of exo-hydroxyfructal
ester 13 in anhydrous pyridine (75mL) and the mixture
was stirred at 60ꢁC for 24h, whereafter TLC (toluene/
EtOAc, 10:1) indicated complete conversion. This was
followed by concentration in vacuo to about one-third,
dilution with water (250mL), extraction with Et2O
(3 · 150mL), and successive washing of the combined
ether extracts with water, 2M HCl, satd NaHCO3
solution (2 · 50mL each), and again with water
(50mL). Drying over Na2SO4 and removal of the
solvent in vacuo provided a syrup, which was purified
by quick elution from a short silica gel column with
4.8. (3R,4S)-3,4-Bis(benzoyloxy)-6-vinyl-3,4-dihydro-2H-
pyran 18
Methyl triphenylphosphonium bromide (734mg,
2.1mmol) was suspended in anhydrous THF (50mL),
and after thorough flushing with dry nitrogen (15min),
1.4mL (2.2mmol) of a 1.6M solution of n-butyl lithium
in n-hexane was added dropwise at ambient tempera-
ture. After 30min, the reaction mixture was cooled to
À10ꢁC, a solution of enal 19 (320mg, 0.9mmol) in
anhydrous THF (5mL) was added dropwise. Stirring
at À10ꢁC under N2 was continued for 24h, whereafter
TLC indicated complete conversion (19: Rf 0.59 in
20:1 CH2Cl2/EtOAc). The mixture was hydrolyzed with
water (40mL) followed by extraction with CH2Cl2
(3 · 25mL) and dried over Na2SO4. Removal of the sol-
vent in vacuo, followed by further purification of the
residue by quick elution from a silica gel column
(3 · 15cm) with CH2Cl2/EtOAc (19:1), and concentra-
tion of the fractions containing 18 gave a colorless syr-
toluene/EtOAc (20:1): 3.5g (73%) of 15 as a colorless
20
D
syrup; ½aŠ ¼ þ205:3 (c 1.0, CHCl3). 1H NMR
(300MHz, CDCl3): d 4.41 (m, 2H, 2CH2), 5.37 (d, 1H,
H-5), 5.62 (m, 1H, H-3), 5.94 (dd, 1H, H-4), 7.32–
8.00 (m, 10H, 2C6H5), 7.60 (s, 1H, CHN), 9.54 (br S,
1H, NOH); J2,4 = 0.4, J3,4 = 4.2, J4,5 = 4.8Hz. 13C
NMR (75.5MHz, CDCl3): d 64.0 (C-4), 64.1 (C-2),
65.9 (C-3), 103.5 (C-5), 128.4–133.4 (C6H5), 144.6
(CHN), 150.2 (C-6), 165.4, 165.9 (2BzCO). MS (FD)
m/z 367 (M+). Anal. Calcd for C20H17NO6 (367.4): C,
65.39; H, 4.66; N, 3.81. Found: C, 63.37; H, 4.68; N,
3.75.
4.6. (3R,4S)-3,4-Bis(benzoyloxy)-6-formyl-3,4-dihydro-
2H-pyran O-benzoyloxime 16
up, which crystallized from 10:1 iPrOH/Et2O: 174mg
20
Benzoylchloride (0.4mL, 3.4mmol) was added dropwise
to a vigorously stirred solution of 500mg (1.4mmol) of
oxime 15 in anhydrous pyridine (20mL). After 24h at
ambient temperature, the reaction mixture was
quenched with water (1mL). The residue obtained after
concentration in vacuo was diluted with CH2Cl2
(25mL), followed by filtration, and washing with 2M
HCl (3 · 25mL), NaHCO3 solution, and water
(2 · 15mL). The organic layer was dried over MgSO4
and evaporated to a slightly yellowish syrup, which crys-
(55%); mp 133–134ꢁC; ½aŠ ¼ þ322:6 (c 1.0, acetone).
D
1H NMR (300MHz, CDCl3): d 4.34 (m, 2H, 2H2),
5.11 (d, 1H, H-5), 5.26 (dd, 1H, H-8Z), 5.55 (m, 1H,
H-3), 5.70 (dd, 1H, H-8E), 5.89 (dd, 1H, H-4), 6.13
(dd, 1H, H-7), 7.3–8.0 (m, 10H, 2C6H5); J3,4 = 4.8,
J4,5 = 5.2, J7, (Z) = 10.9, J7,8(E) = 17.2, J8,8 = 1.4Hz. MS
(FD) m/z 350 (M+). Anal. Calcd for C21H18O5
(350.37): C, 71.99; H, 5.18. Found: C, 72.07; H, 5.19.
4.9. (3R,4S)-3,4-Bis(benzoyloxy)-6-formyl-3,4-dihydro-
2H-pyran 19
tallized on trituration with Et2O: 510mg (79%) 16 as col-
20
orless needles; mp 162–165ꢁC, ½aŠ ¼ þ205:5 (c 1.3,
D
CHCl3). 1H NMR (300MHz, CDCl3): d 4.48 (ddd,
1H, H-2a), 4.51 (dd, 1H, H-2b), 5.65 (d, 1H, H-5),
5.67 (ddd, 1H, H-3), 5.99 (dd, 1H, H-4), 7.35–8.12 (m,
15H, 3C6H5), 8.02 (s, 1H, CHN); J2,2 = 10.7, J2,3 = 4.6
and 5.2, J2b,4 = 0.5, J3,4 = 3.9, J4,5 = 4.5Hz; MS (FD)
m/z 471 (M+). Anal. Calcd for C27H21NO7 (471.5): C,
68.78; H, 4.49; N, 2.96. Found: C, 68.75; H, 4.47; N,
2.97.
A solution of oxime 15 (5.8g, 15.8mmol) in acetonitrile
(100mL) and HCl (50mL) was stirred for 20min at
room temp whereafter 70mL of acetaldehyde were
added dropwise. After 3days at ambient temperature,
the reaction mixture was diluted with 1L of water, fol-
lowed by continuous extraction with EtOAc (1L), and
dried over MgSO4. Removal of the solvent in vacuo left
a syrup, which contained 19 as the main product (Rf
0.45 in 4:1 toluene/acetone) apart from small amounts
of a second compound (Rf 0.23). Purification by elution
from a silica gel column (4.5 · 45cm) with 10:1 toluene/
EtOAc, removal of the solvent from the eluate, and sev-
4.7. (2S,4S,5R)-4,5-Bis(benzoyloxy)-2-ethoxy-2-formyl-
tetrahydropyran oxime 17
Oxime 15 (500mg, 1.4mmol) was solved in a stirred mix-
ture of anhydrous CHCl3 (4mL) and absolute EtOH
eral coevaporations with toluene (ꢀ100mL) afforded
20
4.2g (76%) of enal 19 as a solid foam; ½aŠ ¼ þ148:2
D

A. Boettcher, F. W. Lichtenthaler / Tetrahedron: Asymmetry 15 (2004) 2693–2701
2699
(c 1.4, CHCl3). 1H NMR (300MHz, CDCl3): d 4.42
(ddd, 1H, H-2a), 4.49 (dd, 1H, H-2b), 5.69 (ddd, 1H,
H-3), 6.00 (dd, 1H, H-5), 6.07 (ddd, 1H, H-4), 7.20–
7.99 (m, 10H, 2C6H5), 9.30 (s, 1H, CHO); J2,2 = 11.8,
J2,3 = 3.0 and 6.5, J2b,4 = 1.2, J3,4 = 4.0, J3,5 = 0.5,
J4,5 = 3.8Hz. 13C NMR (75.5MHz, CDCl3): d 63.9 (C-
4), 65.0 (C-3), 65.1 (C-2), 114.8 (C-5), 128.2–133.5
(C6H5), 153.2 (C-6), 165.3, 165.5 (2BzCO), 185.9
(CHO). MS (FD) m/z 352 (M+). Anal. Calcd for
C20H16O6 (352.3): C, 57.39; H, 4.58. Found: C, 57.42;
H, 4.65.
C28H24O8 (488.5): C, 68.85; H, 4.95. Found: C, 69.09;
H, 5.02.
4.12. 2-(2-Benzoyloxyacetyl)furan 22
To a cooled (À5ꢁC) solution of endo-hydroxyfructal
ester 14 (400mg, 0.7mmol) in CH2Cl2 (20mL) was
added with stirring 0.15mL (3.5mmol) of dry methanol
followed by 0.1mL (0.85mmol) of SnCl4. The mixture
was then allowed to warm to room temperature. Con-
version of the educt was in favor of 17 (Rf 0.33, TLC
in 10:1 toluene/EtOAc) being reached within 1h. Dilu-
tion with CH2Cl2 (30mL), thorough washing with NaH-
CO3 solution (2 · 50mL) and brine (50mL), drying over
Na2SO4 of the organic phase, and evaporation to dry-
ness gave a residue, which was purified by elution from
a silica gel column (3 · 15cm) with 10:1 toluene/EtOAc.
Evaporation of the eluate to dryness and crystallization
of the residue from diethyl ether furnished 139mg (88%)
of 22 as colorless needles; mp 76–77ꢁC. 1H NMR
(300MHz, CDCl3): d 5.41 (s, 2H, BzOCH2), 6.58 (dd,
1H, H-4), 7.31 (dd, 1H, H-3), 7.44–8.15 (m, 5H,
C6H5), 7.63 (dd, 1H, H-5); J3,4 = 3.6, J3,5 = 0.6,
4.10. (3R,4S)-3,4-Bis(benzoyloxy)-6-(diethoxy)methyl-
3,4-dihydro-2H-pyran 20
Enal 19 (700mg, 2mmol) was dissolved in dry CHCl3
(5mL) and anhydrous EtOH (5mL) and the mixture
stirred for 4d at room temp. After completion of the
addition (monitoring by TLC in 20:1 toluene/EtOAc),
the solvents were removed in vacuo, and the residue
purified by elution from a silica gel column with 20:1 tol-
uene/EtOAc. Concentration of the appropriate eluate
furnished 660mg (78%) of 20 as a colorless syrup;
20
D
½aŠ ¼ þ145:3 (c 1.0, CHCl3). 1H NMR (300MHz,
J4,5 = 1.7Hz. 13C NMR (75.5MHz, CDCl3):
d
CDCl3): d 1.25, 1.26 (two 3H-t, 2EtCH3), 3.63 (m, 4H,
2EtCH2), 4.32 (m, 2H, 2H2), 4.90 (s, 1H, CH(OEt)2),
5.40 (d, 1H, H-5), 5.56 (m, 1H, H-3), 5.88 (dd, 1H,
H-4, 7.30–8.00 (m, 10H, 2C6H5); J3,4 = 4.4,
J4,5 = 4.8Hz; MS (FD) m/z 426 (M+). Anal. Calcd for
C24H26O7 (426.4): C, 67.59; H, 6.14. Found: C, 67.46;
H, 6.04.
65.8 (BzOC), 112.5 (C-4), 117.9 (C-3), 128.5–133.4
(C6H5), 146.8 (C-5), 150.6 (C-2), 166.0 (BzCO), 181.6
(CO). MS (FI) m/z 230 (M+). Anal. Calcd for
C13H10O4 (230.2): C, 67.82; H, 4.38. Found: C, 67.63;
H, 4.37.
4.13. 2-(2-Hydroxyacetyl)furan 23
4.11. (2R,5S)-3,5-Bis(benzoyloxy)-2-(benzoyloxymethyl)-
2-methoxy-5,6-dihydro-2H-pyran 21
An aqueous solution of spirocyclic dihydropyranon 2529
(555mg, 3mmol, in 20mL) was refluxed in the presence
of 1mL of amberlite 120 (H+-form) for 1h, followed by
filtration, evaporation to dryness in vacuo, and purifica-
tion of the brownish residue by elution from a silica gel
column (2 · 30cm) with 25:1 CHCl3/MeOH). Removal
of the solvents left 23 (355mg, 93%), as colorless crystals
of mp 78ꢁC. Lit.:28 mp 78ꢁC.
To a solution of endo-hydroxyfructal ester 14 (520mg,
0.9mmol) in CH2Cl2 (20mL) was added dry methanol
(0.18mL, 4.4mmol) and freshly desiccated molecular
˚
sieves (4A), and the mixture cooled to 0ꢁC. BF3-ether-
ate (0.46mL, 3.9mmol) was then added dropwise in sev-
eral portions. The mixture was then stirred at ambient
temperature for 2days, after which TLC (10:1 toluene/
EtOAc), indicated the absence of educt. Quenching by
pouring into satd NaHCO3 solution (50mL), followed
by extraction with CH2Cl2 (3 · 30mL), and subjection
of the combined organic extracts to washing with 2M
HCl and water (2 · 20mL each), gave after drying over
Na2SO4 and concentration in vacuo, approximately a
5:1 mixture (1H NMR) of 16 and its 2-epimer (a-ano-
mer). Separation was effected on a silica gel column
(3.0 · 25cm) by elution with toluene/EtOAc (35:1).
The main eluate (Rf 0.30, TLC in 10:1 toluene/EtOAc)
afforded upon removal of the solvents in vacuo 320mg
4.14. (2R)-2-(Benzoyloxymethyl)-2-methoxy-2H-pyran-
3(6H)-one 24
˚
Molecular sieves (4A) and methanol (0.2mL) were
added to a CH2Cl2 solution of endo-hydroxyfructal ester
14 (390mg in 30mL), and after cooling to À10ꢁC, SnCl4
(0.20mL, 2.5molarequiv) was added in several portions
with stirring, which was continued for 1.5h at À10ꢁC.
The mixture was then poured into satd NaHCO3 solu-
tion and processed as described for 16. The eluate with
Rf 0.24 (TLC, 10:1 toluene/EtOAc) was evaporated to
dryness in vacuo. Trituration of the residue with diethyl
20
1
(74%) of syrupy 21; ½aŠ ¼ À60:6 (c 1.0, CHCl3). H
ether resulted in crystallization of 24 (127mg, 72%) as
D
20
D
NMR (300MHz, CDCl3): d 3.48 (s, 3H, OCH3), 4.17
(ddd, 1H, H-6a), 4.37 (dd, 1H, H-6b), 4.63, 4.79 (two
1H-d, CH2OBz), 5.57 (ddd, 1H, H-5), 6.36 (dd, 1H,
H-4), 7.14–8.06 (m, 15H, 3C6H5); J4,5 = 6.1, J4,6b = 0.6,
colorless platelets of mp 106–108ꢁC; ½aŠ ¼ À74:3 (c
1
1.1, CHCl3). H NMR (500MHz, CDCl3): d 3.50 (s,
3H, OCH3), 4.42 and 4.57 (two 1H-ddd, 6H2), 4.66,
4.75 (two 1H-d, CH2OBz), 6.18 (ddd, 1H, H-4), 7.07
(ddd, 1H, H-5), 7.4–8.0 (m, 5H, C6H5); J4,5 = 10.5,
J4,6 = 1.8 and 2.5, J5,6 = 1.9 and 3.8, J6,6 = 19.0,
J5,6 = 1.2 and 2.6, J6,6 = 12.9, JCH = 11.2Hz. 13C
2
NMR (75.5MHz, CDCl3): d 50.4 (OCH3), 62.8 (C-6),
63.5 (CH2OBz), 65.7 (C-5), 96.3 (C-2), 113.6 (C-4),
128.3–133.8 (C6H5), 148.8 (C-3), 163.3, 165.9, 166.1
(3BzCO). MS (FD) m/z 488 (M+). Anal. Calcd for
JCH = 11.4Hz. 13C NMR (75.5MHz, CDCl3): d 51.3
2
(OCH3), 60.7 (C-6), 62.4 (CH2OBz), 97.5 (C-2), 124.7
(C-4), 128.3–133.1 (C6H5), 147.7 (C-5), 165.9 (BzCO),

2700
A. Boettcher, F. W. Lichtenthaler / Tetrahedron: Asymmetry 15 (2004) 2693–2701
188.7 (C-3); MS (FI) m/z 262 (M+). Anal. Calcd for
C14H14O5 (262.3): C, 64.12; H, 5.38. Found: C, 64.14;
H, 5.36.
4.16. (2S,5R)-3,5-Bis(benzoyloxy)-2-benzoyloxymethyl-
2-methoxy-5,6-dihydro-2H-pyran 30
To a CH2Cl2 solution of 28 (580mg, 1mmol, in 20mL)
˚
was added methanol (0.2mL), molecular sieves (4A).
After cooling to 0ꢁC, BF3-etherate (0.5mL) and the
mixture were stirred at room temperature for 2days.
4.15. (3S,4R)-3,4,5-Tri(benzoyloxy)-6-benzoyloxymethyl-
3,4-dehydro-2H-pyran 28
Sodium iodide (3.4g, 22.7mmol) on freshly desiccated
˚
molecular sieves (4A) was added to a solution of
Processing as described for 14 ! 21 (vide supra)
20
afforded 335mg (69%) of syrupy 30; ½aŠ ¼ þ63:1 (c
D
1.1, CHCl3). Spectroscopic data corresponded to those
of its enantiomer 21.
10.0g (15.2mmol) 1,3,4,6-tetra-O-benzoyl-a-L-sorbopy-
ranosyl bromide 2726 in dry acetone (100mL). After stir-
ring for 15h, the suspension was cooled to À10ꢁC and
DBU (3.4mL, 23mmol) added dropwise, followed by
stirring overnight at 10ꢁC and for 24h at ambient tem-
perature (TLC monitoring with 10:1 toluene/EtOAc).
The mixture was then taken to dryness in vacuo, sus-
pended in CHCl3 (200mL), filtered, and the filtrate
washed successively with water, 2M HCl, satd NaHCO3
solution, and again with water. Drying over Na2SO4
and removal of the solvent in vacuo left a syrup, which
was purified by fast elution from silica gel (3 · 25cm col-
umn) with 35:1 toluene/Et2O. Concentration of the elu-
ate gave 6.75g (77%) of a solid foam, which had an Rf of
0.59 in 20:1 toluene/Et2O, yet proved (1H NMR) to be a
5:1 mixture of endo-28 and exo-29 products.
4.17. (2S,5R)-3,5-Bis(benzoyloxy)-2-benzoyloxymethyl-
5,6-dihydro-2H-pyran 31
Triethylsilane (0.13mL, 0.82mmol) and BF3-etherate
(0.17mL, 1.35mmol) were added to a cooled (10ꢁC)
solution of 28 in CH2Cl2 (400mg, 0.69mmol in 20mL)
˚
containing 1.5g of molecular sieves (4A). After stirring
for 6h, the mixture was poured into satd NaHCO3 solu-
tion, followed by separation of the organic layer, and
two extractions of the aqueous phase with CH2Cl2
(25mL each). The combined organic phases were succes-
sively washed with 2M HCl and water, dried over
Na2SO4, and taken to dryness in vacuo. The residue
was purified by elution from silica gel (3 · 15cm col-
umn) with 35:1 toluene/ether. Removal of the solvents
and trituration of the solid residue with Et2O gave
205mg (65%) of 31 in the form of colorless needles;
As appreciable separation by chromatography could not
be effected due to nearly identical Rf values, thus the
exo-isomer 29 was removed by a reaction with
hydroxylamine.
20
D
1
mp 131–132ꢁC; ½aŠ ¼ þ6:2 (c 1.0, CHCl3). H NMR
(300MHz, CDCl3): d 3.98 (dd, 1H, H-6a), 4.22 (d, 1H,
H-6b), 4.54 and 4.60 (two 1H-dd, CH2OBz), 4.70 (m,
1H, H-2), 5.49 (m, 1H, H-5), 6.13 (d, 1H, H-4), 7.1–
Hydroxylamine hydrochloride (1.4g, 20mmol) was
added to a solution of 5.20g (9mmol) of the 5:1 mixture
of hydroxysorbal esters 28/29, as obtained above, in
pyridine (60mL). After stirring for 2d at ambient tem-
perature, the mixture was poured into water (500mL),
followed by five extractions with 100mL portions of
CHCl3, and washing of the combined organic phases
with water (2 · 100mL), 2M HCl (2 · 100mL), NaH-
CO3 solution, and again water (2 · 100mL each). Dry-
ing over Na2SO4 and evaporation to dryness in vacuo
left a residue comprising of an approximate 5:1 mixture
of 28 (Rf = 0.60 in 20:1 toluene/EtOAc) and ene-oxime
32 (Rf 0.21). Separation was readily effected by elution
from a silica gel column (3 · 20cm) with 5:1 toluene/
EtOAc. The first fraction contained the endo-product
28, which was isolated as a colorless foam on removal
8.0 (m, 15H, 3C6H5), J2,CH = 2.9 and 4.1, J4,5 = 5.9,
2
J5,6a = 2.4, J6,6 = 12.0Hz. 13C NMR (75.5MHz,
CDCl3): d 63.4 (CH2OBz), 66.5 (C-5), 67.4 (C-6), 72.5
(C-2), 112.8 (C-4), 128.4–134.1 (C6H5), 151.2 (C-3),
164.1, 166.3, and 166.3 (COC6H5); MS (FD) m/z 458
(M+), 353 (M+ÀBz). Anal. Calcd for C27H22O7
(458.47): C, 70.73; H, 4.84. Found: C, 70.68; H, 4.82.
4.18. (3S,4S)-3,4-Bis(benzoyloxy)-6-formyl-3,4-dihydro-
2H-pyran oxime 32
The second fraction obtained on column separation of
the 5:1 mixture of 28 and 32 (cf. above) contained the
product with Rf 0.21 (20:1 toluene/EtOAc), which was
isolated by removal of the solvents as a colorless solid
of the solvents (2.84g, 54% based on bromide 27, 86%
20
based on the mixture 28/29); ½aŠ ¼ þ173:1 (c 1,
(425mg, 11% based on sorbosyl bromide 27);
D
20
D
CHCl3).33 1H NMR (300MHz, CDCl3): d 4.34 (dd,
1H, H-2a), 4.59 (ddd, 1H, H-2b), 4.93 and 5.05 (two
1H-d, CH2OBz), 5.46 (m, 1H, H-3), 5.96 (m, 1H, H-
4), 7.3–8.2 (m, 20H, 4C6H5), J2,2 = 12.3, J2,3 = 1.3 and
2.5, J2,4 = 1.4, JCH = 12.8. 13C NMR (75.5MHz,
CDCl3): d 59.3 (CH22OBz), 64.4 (C-2), 65.7 (C-4), 68.0
(C-3), 125.7 (C-5), 147.1 (C-6), 128.4–133.7 (C6H5),
165.3, 165.3, 166.1 (BzCO). MS (FD) m/z 578 (M+).
Anal. Calcd for C34H26O9 (578.6): C, 70.58; H, 4.53.
Found: C, 70.47; H, 4.50.
½aŠ ¼ þ243:5 (c 1.1, CHCl3). 1H NMR (300MHz,
CDCl3): d 4.35 (dd, 1H, H-2a), 4.59 (ddd, 1H, H-2b),
5.43 (m, 1H, H-4), 5.49 (dd, 1H, H-5), 5.54 (m, 1H,
H-3), 7.4–8.1 (10H-m, 2C6H5), 7.59 (s, 1H, CHN),
8.40 (s, 1H, NOH), J2,2 = 12.3, J2,3 = 1.7 and 3.0,
J2b,4 = 1.6, J3,5 = 1.4, J4,5 = 5.1Hz. MS (FD) m/z 367
(M+). Anal. Calcd for C20H17NO4 (357.36): C, 65.39;
H, 4.66; N, 3.81. Found: C, 65.28; H, 4.70; N, 3.69.
4.19. (3S,4S)-3,4-Bis(benzoyloxy)-6-formyl-3,4-dihydro-
2H-pyran O-benzoyloxime 33
The second fraction eluted contained the minor prod-
uct, ene-oxime 32. Isolation and characterization cf.
below.
To a cooled solution (0ꢁC) of oxime 32 (200mg,
0.56mmol) in CH2Cl2 (10mL) and pyridine (10mL)

A. Boettcher, F. W. Lichtenthaler / Tetrahedron: Asymmetry 15 (2004) 2693–2701
2701
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14. Nitz, M.; Bundle, D. R. J. Org. Chem. 2001, 66,
8411–8423.
15. Lichtenthaler, F. W.; Lergenmuller, M.; Schwidetzky, S.
¨
Eur. J. Org. Chem. 2003, 3094–3103.
16. Lichtenthaler, F. W.; Jarglis, P. Tetrahedron Lett. 1980,
21, 1429–1432.
17. Jarglis, P.; Lichtenthaler, F. W. Angew. Chem. 1982, 94,
140–141; Angew. Chem. Int., Ed. Engl. 1982, 21, 141–142;
Angew. Chem. Suppl. 1982, 175–184.
18. Brehm, M.; Dauben, W. G.; Ko¨hler, P.; Lichtenthaler,
F. W. Angew. Chem. 1987, 99, 1318–1319; Angew. Chem.
Int., Ed. Engl. 1987, 26, 1271–1273.
19. Lichtenthaler, F. W.; Kraska, U. Carbohydr. Res. 1977,
58, 363–377.
was added benzoyl chloride (0.2mL, 0.17mmol) with
stirring. The mixture was then allowed to stand at room
temperature for 24h, followed by processing as de-
scribed for the fructose-derived analog (15 ! 16):
223mg (84%) of 33 as colorless needles; mp 176–
20
177ꢁC; ½aŠ ¼ þ183:7 (c 1.0, CHCl3). 1H NMR
D
(300MHz, CDCl3): d 4.39 (dd, 1H, H-2a), 4.68 (ddd,
1H, H-2b), 5.47 (m, 1H, H-3), 5.58 (ddd, 1H, H-4),
5.77 (dd, 1H, H-5), 8.00 (s, 1H, CHN), 7.4–8.1 (m,
15H, 3C6H5); J2,2 = 12.4, J2,3 = 1.6 and 2.9, J2b,4 = 1.8,
J3,5 = 1.2, J4,5 = 5.1Hz. Anal. Calcd for C27H21NO7
(471.47): C, 68.78; H, 4.49; N, 2.97. Found: C, 68.65;
H, 4.50; N, 3.00.
20. DeFina, G. M.; Varela, O.; de Lederkremer, R. M.
Synthesis 1988, 891–893.
Acknowledgements
21. Lichtenthaler, F. W.; Nishiyama, S.; Ko¨hler, P.; Lindner,
H. J. Carbohydr. Res. 1985, 136, 13–26.
22. Tokuyama, K.; Katsuhara, M. Bull. Chem. Soc. Jpn. 1966,
39, 2728–2733.
Support of this work by the Fonds der Chemischen
Industrie is gratefully acknowledged.
23. Paulsen, H.; Ko¨ster, H.; Heyns, K. Chem. Ber. 1967, 100,
2669–2680.
References
24. Katsuhara, M.; Wakahara, S.; Tokuyama, K. Bull. Chem.
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4. (a) For generation of 2-hydroxyglycals with highly acid- or
base-sensitive O-protection recent procedures comprising
b-elimination of anomeric sulfoxide4b or selenoxide4c
substituents are likely to be more appropriate; (b) Liu,
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In Modern Synthetic Methods; Scheffold, R., Ed.; VCH
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8. Lichtenthaler, F. W.; Kla¨res, U.; Lergenmuller, M.;
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Schwidetzky, S. Synthesis 1992, 179–184.
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10. Lichtenthaler, F. W.; Kaji, E.; Weprek, S. J. Org. Chem.
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11. (a) Lichtenthaler, F. W.; Schneider-Adams, T. J. Org.
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29. Lichtenthaler, F. W.; Doleschal, W.; Hahn, S. Liebigs
Ann. Chem. 1985, 2454–2464.
30. Grynkiewicz, G. Carbohydr. Res. 1984, 128, C9–C10.
31. The high negative rotation of (2R,6S)-dihydropyranone 10
(À168.8 in CHCl3) contrasts with the considerably smaller
value for its isopropyl analog 11 (À720) and the equally
small positive rotation of enolone ester 9 (+3.619).
Compound 10 nevertheless has a (2R,6S)- or a-D-config-
uration followed from the small allylic J5,6 couplings of
1.7–1.8Hz uniformly observed for 9–11, whilst the b-D-
anomers invariably have J5,6 values in the 3–3.5Hz
range.19 Moreover, the acetylated analog of 10 had
an [a]D of À87.6 and J5,6 of 1.6Hz, the 2-epimeric b-D-
analog À116.4 and 3.0Hz. Ko¨ll, P.; Klenke, K.;
Eisermann, D. J. Carbohydr. Chem. 1984, 3, 403–415;
Obviously, in peracylated dihydropyranones of type
10 unlike those carrying 2-alkoxy substituents––the usual
0E-conformation (cf. Lichtenthaler, F. W.; Ro¨nninger, S.;
Lindner, H. J.; Immel, S. Carbohydr. Res. 1993, 249,
305–324, is substantially distorted toward the 0H2
halfchair).
32. Ness, R. K.; Fletcher, H. G., Jr. J. Org. Chem. 1968, 33,
181–184.
33. For a side product obtained on HgCl2-promoted adenyl-
ation of 27, believed to be 28, a substantially lower
20
rotation {½aŠ ¼ þ121 in CHCl3} was reported;23 obvi-
D
ously the product was impure, containing substantial
amounts of the exo-isomer 30.
12. Lichtenthaler, F. W.; Kla¨res, U.; Szurmai, Z.; Werner, B.
Carbohydr. Res. 1997, 305, 293–303.