Stereocontrolled synthesis of 1,3,5-triols by an iteration of asymmetric dihydroxylation and deoxygenation

FULL PAPER

DOI: 10.1002/ejoc.201000280

Stereocontrolled Synthesis of 1,3,5-Triols by an Iteration of Asymmetric

Dihydroxylation and Deoxygenation

Patrick Walleser^[a]and Reinhard Brückner*^[a]

Dedicated to Professor Bernd Giese on the occasion of his 70th birthday

Keywords: Asymmetric dihydroxylation / Asymmetric synthesis / Deoxygenation / Diastereoselectivity / Samarium

reagents / Skipped polyols

Asymmetric dihydroxylation of the C^γ=C^δbonds in trans-con-

figured α,β,γ,δ-unsaturated esters, carbonate formation, and

Pd⁰-catalyzed deoxygenation of C^γprovided α,β-unsaturated

δ-hydroxy esters. Protection and chain-extension provided

the corresponding α,β-unsaturated ketones. Their asymmet-

ric dihydroxylation in the presence of phenylboronic acid de-

livered dioxaborolanes. SmBr₂-mediated deoxygenation of

C^α, followed by Narasaka–Prasad and Claisen–Tishchenko

reductions, respectively, selectively provided monoprotected

^1,3syn,^3,5syn-, ^1,3syn,^3,5anti-, ^1,3anti,^3,5syn-, and ^1,3anti,^3,5anti-

configured 1,3,5-triols. Enones with a bulky OSiR₃group at

C^δwere dihydroxylated with significantly poorer syn (vs.

anti) selectivities. Dominating reagent control modulated by

opposing (“mismatched case”) or enhancing (“matched

case”) substrate control, respectively, might be responsible.

Introduction

1,3,5-Polyols without substituents at their C², C⁴, C⁶, etc.

centers represent the core structure of the polyol/polyene

macrolide antibiotics.^[1]Although the OH groups are inter-

spersed regularly, they are configured irregularly, forming

random sequences of syn- and anti-configured 1,3-diol

units.^[2]Synthesizing larger arrays of such polyols in a ste-

reocontrolled manner is a challenge – particularly when

striving for convergency. In our laboratory, Körber and

Risch approached this problem in an unprecedented man-

ner^[3,4](Scheme 1, left-hand column),^[5]starting by sub-

jecting the α,β-unsaturated ketones trans-1 to an asymmet-

ric dihydroxylation (“AD”), which delivered α,β-dihydroxy

ketones with almost 100% ee. Samarium(II) iodide was

added, with or without prior protection of the OH group,

to cleave the C^α–O bond while leaving the C^β–O bond in-

tact. The β-hydroxy ketones 5 resulted, which upon further

reduction gave syn- or anti-configured 1,3-diols.

The current study was undertaken in order to extend the

described strategy – which has recently been embellished^[6]

–

to the vinylogous case (Scheme 1, right-hand column): the

α,β,γ,δ-unsaturated ketones (“dienones”) trans,trans-2

should be convertible by γ,δ-selective AD, protection

Scheme 1. Left: Körber/Risch strategy for the synthesis of the enan-

tiomerically pure β-hydroxy ketones 5 from the enones trans-1.

Right: extendability to the vinylogous case: that is, the synthesis of

enantiomerically pure δ-hydroxy enones (unprotected: 6; protected:

6-PG) from the trans,trans-dienones 2.

[a] Institut für Organische Chemie und Biochemie,

Albert-Ludwigs-Universität,

Albertstr. 21, 79104 Freiburg, Germany

Fax: +49-761-2036100

E-mail: reinhard.brueckner@organik.chemie.uni-freiburg.de

View this journal online at

wileyonlinelibrary.com

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Eur. J. Org. Chem. 2010, 4802–4822

1,3,5-Triols by Asymmetric Dihydroxylation and Deoxygenation

(optional), and γ-selective C–O bond rupture into the α,β-

unsaturated δ-hydroxy ketones (“δ-hydroxy enones”) 6.

Protection of the OH group should furnish the function-

alized enones 6-PG. These would be a subset of substrates

of type 1 and so should be amenable to the reaction se-

quence previously discussed for the simple enones 1.

This plan warrants a few comments. One prerequisite for

achieving it was fulfilled, because the all-trans-configured

α,β,γ,δ-unsaturated ketones undergo ADs with the required

regioselectivity.^[7]The same is true from analogous starting

esters and Weinreb amides.^[7b,7i]These findings were re-

assuring in view of the possibility that we might be forced –

as eventually we were – to modify the original idea. The

second prerequisite for tackling the dienones trans,trans-2

as envisaged was that their AD products – whether pro-

tected (4) or unprotected (not shown) – should lose their

C^γ–O bonds when combined with a reductant. No such re-

action based on Sm^IIreagents had been described, although

Pd⁰-catalyzed hydrogenolysis was an established means for

breaking C^γ–O bonds in cyclic carbonates derived from γ,δ-

dihydroxylation products of α,β,γ,δ-unsaturated esters (“di-

enoates”). The same kind of carbonates, as well as the anal-

ogous sulfites or acetonides, also undergo SmI₂-induced

C^γ–O bond cleavage but their C^α=C^βbonds migrate to be-

come C^γ=C^δbonds.^[8]

Depending on whether the dihydroxylation of the pro-

tected δ-hydroxy enones 6-PG were to be performed with

AD mix-β or AD mix-α, the resulting C^α–O/C^β–O bond

pair would be syn- or anti-oriented, respectively, relative to

the C^δ–O bond (Scheme 2). If our AD reaction could be

executed under Muñiz’s and Hövelmann’s conditions^[9]it

would yield the boronates syn- and anti-7 rather than the

parent glycols. The Muñiz–Hövelmann procedure extends

Narasaka’s vic-cis-dihydroxylation/diol phenylboronylation

protocol from racemic products^[10]to materials of Ն98% ee.

In our laboratory it was applied to α,β-unsaturated ketones

for the first time.^[6]The attractiveness of the Muñiz–Hövel-

mann 1-pot transformation in this context is due to the

susceptibility of the resulting ketoboronate to reduction by

Scheme 2. Elaboration of protected (6-PG) δ-hydroxy enones into

the syn,syn-, syn,anti-, anti,syn-, and anti,anti-1,3,5-triols 9.

showed up^[3]or did not^[3,16b,16c]or were obscured by the

competing effect of another remote stereocenter.^[16a]ADs

of free or O-protected δ-hydroxy enoates have been studied

more frequently^[17]but with no emphasis on investigation

of C^δ-OPG or C^δ-OH effects.

Results and Discussion

The generic trans,trans-2 structure of the dienone sub-

Sm^IIreagents: a SmI₂-mediated C^α–O rather than C^β–O strates for this study was accessed with the substitution pat-

cleavage in the boronates syn- and anti-7 would lead to the terns trans,trans-14a and trans,trans-14b (Table 1). These are

hemiprotected β,δ-dihydroxy ketones syn- and anti-8, methyl ketones with either a propyl (a) or an isopropyl sub-

respectively. Their free OH groups should control inter- or stituent (b) at C^δ. A Wittig reaction between hex-2-enal

intramolecular hydride deliveries such that the ^1,3syn- and (11a) and the corresponding ylide gave the desired dienone

^1,3anti-configured monoprotected 1,3,5-triols 9, respectively, 14a as a 97:3 mixture of the ^α,βtrans,^γ,δtrans and the

would be produced. Specifically, Narasaka–Prasad re- ^α,βtrans,^γ,δcis isomers. The corresponding Horner–Wads-

ductions were expected to deliver the triols ^1,3syn,^3,5syn- worth–Emmons reaction produced these isomers in a 93:7

and ^1,3syn,^3,5anti-9^[11,12]and Claisen–Tishchenko^[13,14]or ratio. None of the mixtures was separable by flash

Evans^[15]reductions the ^1,3anti,^3,5syn- and ^1,3anti,^3,5anti-9 chromatography on silica gel.^[18]Surprisingly, Horner–

epimers.

Wadsworth–Emmons reactions^[19]performed in otherwise

Contemplating how well the transformations shown in analogous manner furnished the elusive dienone 14a’s dien-

Scheme 1–Scheme 2 might be turned into practice, we real- oate counterparts 12a and 12b as pure ^α,βtrans,^γ,δtrans iso-

ized that the AD step 6-PGǞ7 was critical: 100% reagent mers (Table 1). From the esters 12a and 12b we proceeded

control of diastereoselectivity was desired – but might the to the ketones 14a and 14b – which were isomerically pure

OPG group at the C^δstereocenter interfere by contributing when prepared in this manner – in two steps and 71% and

some substrate control of diastereoselectivity? We are aware 79% yields, respectively. The intermediates en route were

of the stereochemical outcomes of very few ADs of δ-oxy- the Weinreb amides (“dieneamides”) 13a and 13b^[20]and

genated enones 6 or 6-PG.^[3,16]C^δ-OPG effects variously the source of the methyl group was MeLi.^[21]

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P. Walleser, R. Brückner

FULL PAPER

Table 1. Synthesis of the trans,trans-configured α,β,γ,δ-unsaturated

esters 12, Weinreb amides 13, and ketones 14.^[a]

Table 2. AD of the trans,trans-configured α,β,γ,δ-unsaturated esters

12, Weinreb amides 13, and ketones 14 under Sharpless’ condi-

tions.^[a]

[a] Reagents and conditions: a) NaH (60% dispersion in mineral oil,

1.8 equiv.), THF, –10 °C, addition of 10 (1.7 equiv.), 1 h; addition

of 11, 1 h. b) 12, Me(MeO)NH·HCl (3.0 equiv.), THF, –30 °C, ad-

dition of iPrMgCl·LiCl (6.0 equiv.), 30 min. c) THF, –20 °C, ad-

dition of MeLi (2.2 equiv.), 1 h;Ǟ0 °C, 2 h.

[a] Reagents and conditions: a) “Improved”^[22]AD mix-β [i.e.,

K₂OsO₂(OH)₄(1 mol-%), (DHQD)₂PHAL (5 mol-%), K₃Fe(CN)₆

(3.0 equiv.), K₂CO₃(3.0 equiv.)], NaHCO₃(3.0 equiv.), MeSO₂NH₂

(1.0 equiv.), tBuOH/H₂O (1:1, v/v), 0 °C, 4 d. [b] Separated from

initial 98:2 mixture with the C^α=C^β-dihydroxylation product.

[c] Separated from initial 96:4 mixture with the C^α=C^β-dihydrox-

ylation product.

The dienoates trans,trans-12a and trans,trans-12b and the

dieneamides trans,trans-13a and trans,trans-13b being as

handy as the dienones trans,trans-14a and trans,trans-14b,

we decided to subject each compound to as many as pos-

sible of the seven or so key transformations shown in

Schemes 1 and 2 (round #1 transformations: γ,δ-AD, in situ

or explicit diol protection, γ-defunctionalization, alcohol

protection; round #2 transformations: α,β-AD, in situ or

explicit diol protection, α-defunctionalization; terminating

step: ketone reduction, i.e., triol production). This broad

approach should allow identification of the best suited sub-

strate for our endeavor in terms of chemical yield, regiose-

lectivity, and enantioselectivity.

(Scheme 3). Coincidentally, the last transformation was also

a plausible prerequisite for a C^γ–O bond scission by Pd⁰-

catalyzed hydrogenolysis as described by O’Doherty et

al.^[26]These workers obtained the highest yields with the

cyclic carbonates rather than with open-chain mixed car-

bonates or dibenzoates of γ,δ-dihydroxy enoates.

The AD reactions summarized in Table 2 were effected

under Sharpless’ “improved” conditions^[22][i.e., with em-

ployment of 1 mol-% rather than 0.2 mol-% of K₂OsO₂-

(OH)₄as an Os^VIIIprogenitor and 5 mol-% rather than

1 mol-% of (DHQD)₂PHAL as a chiral auxiliary^[23]]. This

saved costs relative to the conditions of O’Doherty and

Zhang; their ADs of conjugated dienoates used 10 mol-%

OsO₄and 11 mol-% (DHQD)₂PHAL or (DHQ)₂PHAL.^[7i]

The γ,δ-dihydroxy enoates 15a(b) were obtained from the

dienoates 12a(b) in 66% (78%) yield and with 98%

(98.5%) ee after separation from their initial 98:2 (96:4)

mixtures with the α,β-dihydroxy enoates. Perfect regiocon-

trol was observed in the ADs of the dieneamides 16a and

16b (58–84%, 96.6–98.9% ee) and of the dienones 17a and

Scheme 3. Synthesis of the γ,δ-dihydroxy enones 20, 18, and 25a.

Reagents and conditions: a) PhB(OH)₂(1.2 equiv.), CH₂Cl₂, room

temp., 24 h; 85%. b) Triphosgene (1.1 equiv.), pyridine (5.0 equiv.),

CH₂Cl₂, 0 °C, 1.5 h; 95%. c) “Improved”^[22]AD mix-β [i.e., K₂-

OsO₂(OH)₄(1.0 mol-%), (DHQD)₂PHAL (5 mol-%), K₃Fe(CN)₆

17b (52–55%, 97.2–98.2% ee values). The absolute configu- (3.0 equiv.), K₂CO₃(3.0 equiv.)], NaHCO₃(3.0 equiv.), MeSO₂NH₂

(1.0 equiv.), tBuOH/H₂O (1:1, v/v), 0 °C, 20 h; 70%. d) Cam-

phorsulfonic acid (5 mol-%), 2,2-dimethoxypropane (36 equiv.), no

additional solvent, room temp., 3 h; 66%.

ration of each product is assumed to comply with

“Sharpless’ mnemonic”.^[24]

Earlier experiences had taught that α,β-dihydroxy

ketones can be, but do not need to be, derivatized before

In exploratory experiments (Table 3), γ-defunctionali-

SmI₂cleaves their C^α–O bond efficiently.^[5]Nevertheless, the zation of the dihydroxy enone derivatives 20 (acetonide), 18

unprotected γ,δ-dihydroxy enone 21 decomposed when it (phenylboronate), or 25a (carbonate) discussed above failed

–

+

was exposed to SmI₂.^[25]Accordingly we derived the aceton- in two cases [20 + SmI₂; 18 + HCO₂HNEt₃+ cat.

ide 20 from this diol, and both the phenylboronate 18 and Pd(PPh₃)₄] but worked in the third case: when 25a and

–

+

the carbonate 25a from the γ,δ-dihydroxy enone 17a HCO₂HNEt₃were allowed to react in the presence of

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1,3,5-Triols by Asymmetric Dihydroxylation and Deoxygenation

cat. Pd₂(dba)₃·CHCl₃/PPh₃the desired hydroxy enone 28a

Table 5 lists the ensuing Pd₂(dba)₃·CHCl₃-catalyzed

resulted. It was the major constituent of a 89:11 mixture C^γ–O bond scissions in the γ,δ-carbonatoesters 23a and

(72% yield) with the isomer with a C^β=C^γrather a C^α=C^β23b, the γ,δ-carbonatoenamides 24a and 24b, and the γ,δ-

bond (iso-28a; formula in Table 5) and could not be sepa- carbonatoenones 25a and 25b. Yields were highest for the

rated therefrom. In O’Doherty’s γ-defunctionalization of esters (Ǟ 71–73%), somewhat lower for the ketones (Ǟ55–

the carbonates of dihydroxy enoates the C=C bond stayed 72%), and smallest for the amides (Ǟ30–65%). The inter-

fixed.^[26]That carbonate 25a was attacked by Pd⁰but the ference of C^α=C^βǞC^β=C^γshifts was almost negligible for

corresponding phenylboronate 18a was not was no real sur- the esters (Ǟ3–4% bond-shift) but sizable for the Weinreb

prise: enoate-containing phenylboronates are obtained in the amides (Ǟ10–11% bond-shift) and still greater for the

presence of Pd(PPh₃)₄from γ,δ-epoxy enoates and phen- ketones (Ǟ11–18% bond-shift). Purification by flash

ylboronic acid.^[27]

chromatography on silica gel^[18]allowed us to isolate the

corresponding mixtures of C^α=C^β(26a/b^[28]–28a/b) and

C^β=C^γ(iso-26a/b–iso-28a/b) isomers but turned out to be

insufficient for obtaining the desired major components iso-

merically pure. As a consequence we considered the “genu-

ine” mixtures of the Weinreb δ-hydroxy enamides 27a/27b/

iso-27a/iso-27b or of the δ-hydroxy enones 28a/28b/iso-28a/

iso-28b to be less well suited than the δ-hydroxy enoates

26a/26b with their “tiny” isomer contents for perusal in our

proceedings. Accordingly, we disregarded processing of 27a/

27b/iso-27a/iso-27b or 28a/28b/iso-28a/iso-28b any further

and focused on 26a (as a 97:3 mixture with iso-26a) and

26b (as a 96:4 mixture with iso-26b) as the sources of our

1,3,5-triols.

Table 3. Attempted γ-deoxygenation of the γ,δ-dihydroxy enones

18, 20, and 25a.^[a]

X

R

Reagent(s)

Yield

[%]

C^α=C^β

:

C^β=C^γ

[b]

20

18

CMe₂Ph

BPh Pr

25a C=O

SmI₂

22

28a

–

[c]

Pd(PPh₃)₄

Pd₂(dba)₃·CHCl₃,

PPh₃

–

72

89:11

Table 5. Palladium catalyzed γ-deoxygenation of carbonates 23–

25.^[a]

[a] Reagents and conditions: a) SmI₂(2.2 equiv.), THF, –78 °C, ad-

dition of substrate in THF/MeOH/HMPA (10:1:5, v/v/v);Ǟroom

temp., 30 min. b) Pd(PPh₃)₄(2.5 mol-%), NEt₃(3.1 equiv.),

HCO₂H (3.1 equiv.), THF, reflux, 2 h. c) Pd₂(dba)₃·CHCl₃

(2.5 mol-%), PPh₃(6.3 mol-%), NEt₃(3.1 equiv.), HCO₂H

(3.1 equiv.), THF, reflux, 2 h. [b] Decomposition, no 20 reisolated.

[c] Partial decomposition, 51% 18 reisolated.

The screening results shown in Table 3 allowed us to con-

vert not only the γ,δ-dihydroxy enone 17b but also the γ,δ-

dihydroxy enoates 15a and 15b and their Weinreb amides

16a and 16b into cyclic carbonates (Table 4). This occurred

in 72–95% yields under O’Doherty’s conditions for carbon-

ate formation from γ,δ-dihydroxy enoates^[26a](i.e., by expo-

sure to triphosgene and pyridine in CH₂Cl₂).

Table 4. Carbonate formation from the α,β-unsaturated γ,δ-dihy-

droxy esters 15, the Weinreb amides 16, and the ketones 17.^[a]

[a] Reagents and conditions: a) HCO₂H (3.1 equiv.), NEt₃

(3.1 equiv.), Pd₂(dba)₃·CHCl₃(2.5 mol-%), PPh₃(6.3 mol-%), THF,

reflux, 2 h.

It was gratifying to find that protection of the OH groups

of the δ-hydroxy enoates 26a/26b/iso-26a/iso-26b delivered

the mixed acetals 29a and 29b (“BOM ethers”), the para-

methoxybenzyl ethers 30a and 30b (“PMB ethers”), and the

tert-butyldiphenylsilyl ethers 31a and 31b (“TBDPS

ethers”) in 70–98% yields and that flash chromatography on

silica gel^[18]removed the C^β=C^γ-containing contaminant in

each instance (Table 6). Benzylation was successful only

with PMB-OC(=NH)CCl₃, but the reaction, lasting 11

days, was still tedious. The O-protected δ-hydroxy enoates

29a/b–31a/b were carried on via the Weinreb amides^[20]32a/

b–34a/b to the corresponding methyl ketones^[21]35a/b–37a/

b in good to excellent overall yields.

[a] Reagents and conditions: a) Triphosgene (1.1 equiv.), pyridine

(5.0 equiv.), CH₂Cl₂, 0 °C, 1.5 h.

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P. Walleser, R. Brückner

FULL PAPER

Table 6. Protection of the δ-oxygenated α,β-unsaturated esters 26a

and 26b and their subsequent conversion into isomer-free protected

α,β-unsaturated Weinreb amides and ketones.^[a]

Table 7. AD of the protected δ-hydroxy enones 35–37 under Muñ-

iz’s conditions.^[a]

[a] Reagents and conditions: a) BOM-Cl (4.0 equiv.), NEt₃

(4.0 equiv.), 1,2-dichlorethane, reflux, 4 h. b) PMB-OC(=NH)CCl₃

(2.3 equiv.), pyridinium p-toluenesulfonate (0.6 equiv.), CH₂Cl₂,

room temp., 11 d. c) TBDPS-Cl (2.0 equiv.), imidazole (4.0 equiv.),

DMF, 65 °C, 2 d. d) Me(MeO)NH·HCl (3.0 equiv.), THF, –30 °C,

addition of iPrMgCl·LiCl (6.0 equiv.), 30 min. e) 32–34, THF,

–20 °C, addition of MeLi (2.2 equiv.), 1 h; Ǟ0 °C, 2 h. [b] Incom-

plete conversion, 15% 26a reisolated. [c] Incomplete conversion,

21% 26b reisolated.

[a] Reagents and conditions: a) “Improved”^[22]AD mix-α [i.e.,

K₂OsO₂(OH)₄(1 mol-%), (DHQ)₂PHAL (5 mol-%), K₃Fe(CN)₆

(3.0 equiv.), K₂CO₃(3.0 equiv.)], NaHCO₃(3.0 equiv.), PhB(OH)₂

(1.2 equiv.), tBuOH/H₂O (1:1, v/v), 0 °C, 2 d. b) Same as (a), but

with (DHQD)₂PHAL instead of (DHQ)₂PHAL.

in this group of compounds. Accordingly the stereochemi-

cal identities of compounds syn- and anti-38–40 are based

solely on the validity of Sharpless’ mnemonic.^[24]

The enone BOM ethers 35a and 35b, PMB ethers 36a

and 36b, and tert-butyldiphenylsilyl ethers 37a and 37b were

subjected to the AD reactions summarized in Table 7. With

(DHQD)₂PHAL on the one hand and with (DHQ)₂PHAL

on the other for controlling the facial selectivity of C=C

attack, we expected^[24]the newly formed C^α–O and C^β–O

bonds to be syn- and anti-oriented, respectively, relative to

the previously introduced C^δ–O bond. The inherently low

reactivities of the electron-deficient C=C bonds in our sub-

strates were overcome by use of the “improved” condi-

tions^[22]that we had already used for the ADs shown in

Table 2. Moreover, we added phenylboronic acid to our

AD mixtures^[9]so that we obtained the phenylboronates

38a/b–40a/b rather than the parent diols. Except in the case

of the sterically most hindered substrate (37b), yields were

between 59 and 82%.

The syn- and anti-configured boronates 38a/b–40a/b were

isolated as mixtures. Depending on whether they had been

formed by the action of “improved” AD mix-α^TMor

AD mix-β^TMthe major products prevailed to a significant

extent (71–94%). This allowed us to extract unequivocally

the ¹H and ¹³C NMR shifts of all nuclei in the stereochemi-

cally differentiating string C^5Ј(-H)–C^1ЈЈ(-H_A)(-H_B)–C^2ЈЈ(-H).

The bottom rows of Table 8 and Table 9 list the average

chemical shift difference for each nucleus of this string in

the syn and the anti diastereomer. No single one of these

Table 8. Characteristic ¹H NMR shifts for the syn- and anti-config-

ured dioxaborolanes 38a/b–40a/b in CDCl₃solutions (400 MHz).

PG

R

δ_5Ј–H

δ_1ЈЈ–Hδ_1ЈЈ–Hδ_2ЈЈ–H

A B

[ppm] [ppm] [ppm] [ppm]

syn-

anti-

syn-

anti-

38a BOM

Pr

4.65

4.71

4.68

4.71

1.69

1.86

1.93

1.79

2.06

1.95

2.05

1.89

3.92

4.03

3.67

3.89

38b

iPr

syn-

anti-

syn-

anti-

39a PMB

Pr

4.67

4.71

4.70

1.94

1.87

1.90

1.81

2.07

1.94

2.03

1.86

3.68

3.77

3.45

3.62

39b

iPr

syn-

anti-

syn-

anti-

40a TBDPS Pr

40b iPr

4.61

4.60

4.42

4.48

1.87

1.79

1.68

1.91

1.88

1.91

1.82

4.07

4.10

3.94

3.99

Average value δ_syn-δ_anti

–0.03 +0.12 –0.12 –1.16

The diastereoselectivities of the AD reactions listed in

average values correctly describes the corresponding shift Table 7 are 90–92% for the BOM ethers 35a and 35b and

order in all the compounds. In other words, there is no 92–93% for the PMB ethers 36a and 36b. In the syn series

NMR shift criterion for assigning syn or anti configurations this statement is as valid as in the anti series. The anti-dihy-

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1,3,5-Triols by Asymmetric Dihydroxylation and Deoxygenation

Table 9. Characteristic ¹³C NMR shifts for the syn- and anti-con- 43 and ^1,3syn,^3,5anti-44 when syn-41 was reduced and the

triprotected 1,3,5-triols ^1,3anti,^3,5syn-45 and ^1,3anti,^3,5anti-46

figured dioxaborolanes 38a/b–40a/b in CDCl₃solutions (100 MHz).

when anti-42 was reduced.

PG

R

δ_C–5Ј

[ppm]

δ_C–1ЈЈ

[ppm]

δ_C–2ЈЈ

[ppm]

syn- 38a BOM

anti-

syn- 38b

anti-

Pr

77.39

77.19

79.96

79.91

41.25

42.41

37.83

38.05

74.62

74.08

77.82

77.37

iPr

syn- 39a PMB

anti-

syn- 39b

anti-

Pr

77.47

79.99

80.10

40.61

42.10

36.74

37.88

75.07

75.26

77.94

77.34

iPr

syn- 40a TBDPS

Pr

70.14

69.73

74.38

73.99

43.20

44.13

41.33

39.61

77.04

77.02

77.00

anti-

syn- 40b

anti-

iPr

Average value δ_syn-δ_anti

+0.19

–1.16

+0.30

droxylations of the TBDPS ethers 37a and 37b exhibit vir-

tually identical diastereoselectivities: ds = 89 and 94%,

respectively. In marked contrast, the syn-dihydroxylations

of the TBDPS ethers 37a and 37b revealed no more than 76

and 71% ds.^[29]In principle each substrate of Table 7 allows

stereocontrol through double stereodifferentiation,^[30]so it

appears plausible to invoke matched (Ǟanti-40a/b) vs. mis-

matched (Ǟ syn-40a/b) substrate/reagent pairs to explain

the diastereoselectivities of the ADs of the TBDPS ethers

37a and 37b. Quite differently, there is no such effect in the

ADs of the BOM (35a, 35b) and PMB ethers (36a, 36b), in

which the ds values are invariant to swapping of the addi-

tive. It is tempting to suggest that our combined observa-

tions mean that AD diastereocontrol is completely due to

reagent control with respect to the BOM and PMB ethers

but only partly with respect to the TBDPS ethers. However,

such an interpretation neglects the fact that the diastereo-

selectivities of Table 7 distinctly lag behind typical enantio-

selectivities of ADs of “simple” – and achiral – enones:^[6]

these deliver at least 97% of the preferred enantiomer and

not infrequently Ͼ99%. Accordingly, an attenuation of ste-

reocontrol in AD reactions of enones with increased steric

demand must be diagnosed.

Scheme 4. SmBr₂-mediated α-reductions of the dioxaborolanes syn-

39a and anti-40b to the corresponding monoprotected β,δ-dihy-

droxy ketones syn-41 and anti-42 and subsequent syn- and anti-

selective reductions. Reagents and conditions: a) SmBr₂[0.1  in

THF, 3.2 equiv.; prepared overnight from Sm powder (2.05 equiv.)

and 1,1,2,2-tetrabromoethane (0.5 equiv.)], THF, –78 °C, addition

of substrate in THF/MeOH (2:1, v/v), 90 min. b) BEt₃(1.1 equiv.),

THF/MeOH (4:1, v/v), room temp., 1 h, then –78 °C, addition of

dioxaborolane in THF, 2 h, addition of NaBH₄(1.2-fold molar

quantity), 16 h. c) Isobutyraldehyde (4.0 equiv.), THF, –10 °C, ad-

dition of SmI₂[0.1  in THF, 10 mol-%; prepared overnight from

Sm powder (1.05 equiv.) and 1,2-diiodoethane (1.0 equiv.)], 1 h.

With the finish line approaching, the phenylboronates

syn-39a (92:8 mixture with anti-39a) and anti-40b (94:6 mix-

ture with syn-40b) – those obtained with the highest dia-

stereoselectivities – were deoxygenated at C^α(Scheme 4).

With use of SmBr₂as established by Zörb^[6]this furnished

the δ-protected β,δ-dihydroxy ketones syn-41 and anti-42 in

45% and 60% yields, respectively. These species were chro-

matographically inseparable 91:9 and 93:7 mixtures with

In detail, reductions by the Narasaka procedure^[11,12]did

their corresponding diastereomers. Compound syn-41 was not provide the expected syn-1,3-diol moiety but the derived

then subjected to a pair of highly diastereoselective car- cis-B-ethyldioxaborinanes ^1,3syn,^3,5syn-43 (80% from syn-

bonyl reductions, and anti-42 was treated likewise. As a re- 41; inseparable 92:8 mixture with ^1,3syn,^3,5anti-43) and

sult we completed the diprotected 1,3,5-triols ^1,3syn,^3,5syn- ^1,3syn,^3,5anti-44 (77% from anti-42; inseparable 94:6 mix-

Eur. J. Org. Chem. 2010, 4802–4822

www.eurjoc.org

4807

P. Walleser, R. Brückner

FULL PAPER

ture with ^1,3syn,^3,5syn-44). We are aware of a single litera-

ture report on the formation at all of a 1,3,2-dioxaborinane

under the conditions of a Narasaka–Prasad reduction: the

cis-substituted B-ethylated heterocycle and the syn-config-

ured 1,3-diol arose in a 1:1 ratio.^[12i]At room temp. the

former product gave the latter after 3 h of a K₂CO₃-medi-

ated methanolysis in methanol/ether 3:1.^[31]anti-Selective

Claisen–Tishchenko reductions in the presence of isobutyr-

aldehyde and SmI₂^[13,14]converted syn-41 into ^1,3anti,^3,5syn-

45 (59%) and anti-42 into ^1,3anti,^3,5anti-46 (61%); both

products were 89:11 mixtures with an inseparable dia-

stereomer. In this step the already present protecting group

on O⁵is preserved and an isobutyrate moiety is introduced

on O³.

burg. IR spectra: Perkin–Elmer FT-IR Paragon 1000. Optical rota-

tions (α_exp) were measured with a Perkin–Elmer 341 MC polarime-

ter at 589 nm, 578 nm, 546 nm, 436 nm, and 365 nm/20 °C and cal-

culated according to the Drude equation {[α]_D= (α_expϫ 100)/

(cϫd)}; rotational values are the averages of five measurements of

α_expin a given solution of the sample.

Ethyl (2E,4E)-Octa-2,4-dienoate (12a): NaH [60% dispersion in

mineral oil (3.10 g, 77.6 mmol, 1.8 equiv.)] was suspended in THF

(72 mL) and cooled to –20 °C. Triethyl phosphonoacetate (10,

16.4 g, 73.3 mmol, 1.7 equiv.) was added over a period of 30 min.

After the mixture had been stirred for 30 min at this temperature,

trans-hex-2-enal (5.00 mL, 4.23 g, 43.1 mmol) was added slowly

and the mixture was kept for 20 min at –20 °C. The reaction mix-

ture was then quenched cautiously with satd. aq. NH₄Cl (35 mL).

The phases were separated and the aq. phase was extracted with

MTBE (tert-butyl methyl ether, 3ϫ40 mL). The combined organic

phases were washed with brine (10 mL) and dried with MgSO₄.

After removal of the solvent under reduced pressure, flash

chromatography (4ϫ20 cm, 20 mL, cyclohexane/EtOAc 100:1)

provided the title compound (fractions 8–29, 6.53 g, 90%) as a col-

Conclusions

The Körber/Risch strategy for synthesizing sterically

homogeneous 1,3-diols (including monoprotected variants)

from conjugated enones was elaborated into a vinylogous

strategy of sorts. It leads from conjugated dienoates to steri-

cally homogeneous di- or triprotected 1,3,5-triols. A center-

piece of our approach is the iteration of Sharpless’ enantio-

selective AD reaction – which establishes two C–O bonds –

and a regioselective reduction – which removes one C–O

bond. The last step is a Narasaka–Prasad or Claisen–Tish-

chenko reduction.

orless oil. ¹H NMR (400 MHz, C₆D₆/C₆D₅H): δ = 0.71 (t, J_8,7

=

7.4 Hz, 8-H₃), 1.00 (t, J_2Ј,1Ј= 7.1 Hz, 2Ј-H₃), 1.13 (qt, J_7,8= 7.4,

J_7.6= 7.4 Hz, 7-H₂), 1.75 (m_c, approximately interpretable as tdd,

4

J_6,7= J_6,5= 7.3, J_6,4= 1.3 Hz, 6-H₂), 4.01 (q, J_1Ј,2Ј= 7.1 Hz, 1Ј-

H₃), 5.64 (dt, J_5,4= 15.2, J_5,6= 7.2 Hz, 5-H), 5.86 (m, 5-H), 5.87

(d, J_4,5= 15.4 Hz, 4-H), 7.45 ppm (dd, J_3,2= 15.3 Hz, J_3,4

=

11.2 Hz, 3-H). ¹³C NMR (100 MHz, C₆D₆): δ = 13.64 (C-8), 14.35

(C-2Ј), 22.06 (C-7), 35.01 (C-6), 60.02 (C-1Ј), 120.00 (C-2), 128.91

(C-4), 143.83 (C-5), 145.07 (C-3), 166.76 ppm (C-1). IR (film): ν =

˜

In the resulting 1,3,5-triols (or rather their derivatives)

the configurations of two C–O bonds are imposed by the

choice of the ligand (AD mix-α^TMor AD mix-β^TM). The

configuration of the third C–O bond is determined by sub-

strate control. Importantly, each of the stereochemical con-

trols operates such that it is left entirely to the experiment-

er’s judgement to decide which stereoisomer to go for. This

was illustrated by making a complete set (“library”) of dif-

ferently protected 1,3,5-triols 43–46 with the four possible

accessible combinations of the next-to-vicinal syn or anti

relationships.

3415, 2960, 2935, 2875, 1715, 1645, 1620, 1510, 1465, 1370, 1330,

1305, 1265, 1220, 1180, 1140, 1100, 1040, 1000, 865, 805, 770,

715 cm^–1. HRMS (EI, 70 eV): calcd. for C₁₀H₁₆O₂168.11503

[M]⁺; found 168.11510 (+0.4 ppm).

Ethyl (2E,4E)-6-Methylhepta-2,4-dienoate (12b): This compound

was prepared from (E)-4-methylpent-2-enal (0.90 mL, 0.76 g,

7.74 mmol) as described for 12b. Flash chromatography

(2.5ϫ19 cm, 20 mL, cyclohexane/EtOAc 100:1) provided the title

compound (fractions 5–26, 1.29 g, 99%) as a colorless oil. ¹H

NMR (400 MHz, C₆D₆/C₆D₅H): δ = 0.76 [d, J_7,6and alternatively

J_6-Me,6= 6.7 Hz, 6-(CH₃)₂], 1.00 (t, J_2Ј,1Ј= 7.1 Hz, 2Ј-H₃), 2.02

(qqdd, J_6,5= J_6,6-Me= J_6.7= 6.8, ⁴J_6.4= 1.2 Hz, 6-H), 4.07 (q, J_1Ј,2Ј

= 7.1 Hz, 1Ј-H₂), 5.63 (br. dd, J_5,4= 15.1, J_5,6= 6.9 Hz, 5-H), 5.86

(dddd, J_4,5= 15.4, J_4,3= 10.8, ⁴J_4.6= 1.3, ⁴J_4.2= 0.6 Hz, 4-H), 5.88

(dd, J_2,3= 15.3, ⁴J_2,4= 1.2 Hz, 2-H), 7.44 ppm (ddd, J_3,2= 15.2 Hz,

Experimental Section

General Information: Reactions were performed in oven-dried

(110 °C) glassware under N₂. THF was freshly distilled from K;

CH₂Cl₂was distilled from CaH₂. Products were purified by flash

chromatography^[18](column diameter, filling height, fraction vol-

ume, and eluents are given in parentheses; fractions containing the

isolated product are indicated in each description as “fractions xx–

yy”) on Acros silica gel 60 (0.035–0.060 mm). Yields refer to analyt-

ically pure samples. ¹H NMR [CHCl₃(δ = 7.26 ppm) as internal

standard in CDCl₃or C₆D₅H (δ = 7.16 ppm) as internal standard

in C₆D₆]: Varian Mercury VX 300, Bruker AM 400, and Bruker

DRX 500. Integrals agree with the given assignments. Coupling

constants are given in Hz. ¹³C NMR [CDCl₃(δ = 77.10 ppm) as

internal standard in CDCl₃or C₆D₆(δ = 128.06 ppm) as internal

standard in C₆D₆]: Bruker AM 400 and Bruker DRX 500. Assign-

ments of ¹H and ¹³C NMR resonances refer to the IUPAC no-

menclature except for substituents (where primed position numbers

are used). Combustion analyses: E. Hickl and F. Tönnies. Chiral

HPLC: G. Fehrenbach. MS: Dr. J. Wörth and C. Warth, all at the

Institut für Organische Chemie und Biochemie, Universität Frei-

4

J_3,4= 11.0 Hz, J_3,5= 0.6 Hz, 3-H). ¹³C NMR (100 MHz, C₆D₆):

δ = 14.35 (C-2Ј), 21.70 [6-(CH₃)₂], 31.56 (C-6), 60.02 (C-1Ј), 120.18

(C-2), 125.89 (C-4), 145.30 (C-5), 150.51 (C-3), 166.71 ppm (C-1).

IR (film): ν = 3410, 2965, 2870, 1715, 1645, 1620, 1465, 1365, 1300,

˜

1280, 1260, 1240, 1190, 1145, 1110, 1045, 1000, 875, 830 cm^–1.

HRMS (EI, 70 eV): calcd. for C₁₀H₁₆O₂168.11503 [M]⁺; found

168.11480 (–1.4 ppm).

(2E,4E)-N-Methoxy-N-methylocta-2,4-dienamide (13a): Compound

12a (2.50 g, 14.9 mmol) and Me(MeO)NH·HCl (4.35 g, 23.5 mL,

44.6 mmol, 3.0 equiv.) were dissolved in THF (270 mL) and cooled

to –30 °C. iPrMgCl·LiCl (1.9  in THF, 47.0 mL, 9.2 mmol,

6.0 equiv.) was then added over a period of 1 h. After 30 min at

–30 °C the reaction mixture was quenched cautiously with satd. aq.

NH₄Cl (120 mL), the phases were separated, and the aq. phase was

extracted with MTBE (3ϫ150 mL). The combined organic phases

were washed with brine (120 mL) and dried with MgSO₄. After

removal of the solvent under reduced pressure, flash chromatog-

raphy (3.5ϫ18 cm, 10 mL, cyclohexane/EtOAc 6:1) provided the

4808

www.eurjoc.org

Eur. J. Org. Chem. 2010, 4802–4822

1,3,5-Triols by Asymmetric Dihydroxylation and Deoxygenation

4

title compound (fractions 14–39, 2.16 g, 79%) as a colorless oil. ¹H

10.6, J_5.7= 1.2, J_5.3= 0.6 Hz, 5-H), 5.94 (d, J_3,4= 15.7 Hz, 3-

NMR (400 MHz, C₆D₆/C₆D₅H): δ = 0.73 (t, J_8,7= 7.4 Hz, 8-H₃), H), 6.90 ppm (dd, J_4,3= 15.6 Hz, J_4,5= 10.4 Hz, 4-H). ¹³C NMR

1.18 (qt, J_7,8= J_7,6= 7.4 Hz, 7-H₂), 1.82 (tdd, J_6,7= J_6.5= 7.2, ⁴J_6.4

= 1.4 Hz, 6-H₂), 2.97 (s, NCH₃), 3.08 (s, OCH₃), 5.72 (dt, J_5,4

(100 MHz, C₆D₆): δ = 21.76 [7-(CH₃)₂], 27.04 (C-1), 31.69 (C-7),

126.40 (C-3), 129.51 (C-5), 143.07 (C-6), 150.86 (C-4), 196.46 ppm

=

4

15.1, J_5,6= 7.1 Hz, 5-H), 6.07 (ddtd, J_4,5= 15.1, J_4.3= 11.1, J_4.6

(C-2). IR (film): ν = 3320, 2960, 2930, 2870, 1670, 1635, 1595,

˜

4

= 1.5, J_4.2= 0.7 Hz, 4-H), 6.50 (d, J_2,3= 15.2 Hz, 2-H), 7.71 ppm

1465, 1425, 1360, 1275, 1255, 1235, 1155, 1110, 995 cm^–1. HRMS

(EI, 70 eV): calcd. for C₉H₁₄O 138.1045 [M]⁺; found 138.1045

(+0.2 ppm).

(ddd, J_3,2= 15.2 Hz, J_3,4= 11.2 Hz, ⁴J_3.5= 0.8 Hz, 3-H). ¹³C NMR

(100 MHz, C₆D₆): δ = 13.67 (C-8), 22.14 (C-7), 32.25 [N(CH)

₃(OCH₃)], 35.11 (C-6), 61.02 [N(CH)₃(OCH₃)], 118.11 (C-2),

129.51 (C-4), 143.00 (C-5), 143.88 (C-3), 167.46 ppm (C-1). IR

Ethyl (4R,5R,E)-4,5-Dihydroxyoct-2-enoate (15a): Compound 12a

(1.54 g, 9.13 mmol) was added at 0 °C to a stirred mixture of K₂O-

sO₂(OH)₄(33.7 mg, 1 mol-%), (DHQD)₂PHAL (357 mg, 5 mol-%),

K₃Fe(CN)₆(9.02 g, 27.4 mmol, 3.0 equiv.), K₂CO₃(3.78 g,

27.4 mmol, 3.0 equiv.), NaHCO₃(2.30 g, 27.4 mmol, 3.0 equiv.),

and MeSO₂NH₂(0.87 mg, 9.13 mmol, 1.0 equiv.) in a mixture of

tBuOH and H₂O (1:1, 90 mL). After the system had been kept for

4 d at this temperature, EtOAc (40 mL) was added and the phases

were separated. The aq. phase was extracted with EtOAc

(3ϫ30 mL). The combined organic phases were dried with MgSO₄.

(film): ν = 3405, 2960, 2935, 2875, 1665, 1635, 1465, 1415, 1385,

˜

1180, 1120, 1000 cm^–1. HRMS (EI, 70 eV): calcd. for C₁₀H₁₇NO₂

183.1259 [M]⁺; found 183.1258 (–0.7 ppm).

(2E,4E)-N-Methoxy-N,6-dimethylhepta-2,4-dienamide (13b): This

compound was prepared from 12b (670 mg, 3.98 mmol) as de-

scribed for 13a. Flash chromatography (2ϫ18.5 cm, 10 mL, cyclo-

hexane/EtOAc 5:1) provided the title compound (fractions 13–33,

584 mg, 80%) as a colorless oil. ¹H NMR (400 MHz, C₆D₆/

C₆D₅H): δ = 0.80 (d, J_7,6and alternatively J_6-Me,6= 6.7 Hz, 7-H₆), Removal of the solvent under reduced pressure and flash

4

2.08 (qqdd, J_6,5= J_6,6-Me= J_6,7= 6.8, J_6.4= 1.3 Hz, 6-H), 2.97 (s,

NCH₃), 3.11 (s, OCH₃), 5.72 (br. dd, J_5,4= 15.2, J_5,6= 6.8 Hz, 5-

chromatography (3ϫ14 cm, 20 mL, cyclohexane/EtOAc 4:1) pro-

vided the title compound (fractions 20–38, 1.44 g, 78%) as a color-

less oil. [α]₅²₈⁰₉= +29.3, [α] = +30.8, [α] = +35.2, [α] = +63.2,

4

20

H), 6.06 (dddd, J_4,5= 15.3, J_4,3= 11.1, J_4.6= 1.4, J_4.2= 0.7 Hz,

4-H), 6.51 (d, J_2,3= 15.2 Hz, 2-H), 7.67 ppm (ddd, J_3,2= 15.2 Hz,

578 546 436

20

[α] = +108.2 (c = 0.60, CHCl₃). The ee (98.5%) was determined

365

J_3,4= 10.9 Hz, J_3,5= 0.8 Hz, 3-H). ¹³C NMR (100 MHz, C₆D₆):

by chiral HPLC [Chiralpak AD-H, n-heptane/EtOH (70:30),

4

δ = 21.81 [6-(CH₃)₂], 31.58 (C-6), 32.24 [N(CH)₃(OCH₃)], 61.02 0.8 mLmin^–1, 215 nm]: t_r(4R,5R)= 10.7 min, t_r(4S,5S)= 7.1 min (de-

[N(CH)₃(OCH₃)], 118.31 (C-2), 126.45 (C-4), 14.05 (C-5), 149.71

(C-3), 167.41 ppm (C-1). IR (film): ν = 3480, 2960, 2870, 1660, CHCl₃): δ = 0.93 (dd, J_8,7-H(A)= J_8,7-H(B)= 7.0 Hz, 8-H₃), 1.28 (t,

termined with racemic material). ¹H NMR (400 MHz, CDCl₃/

˜

1630, 1610, 1465, 1415, 1380, 1340, 1215, 1180, 1115, 1090, 1005,

J_2Ј,1Ј= 7.1 Hz, 2Ј-H₃), 1.31–1.58 (m, 6-H₂, 7-H₂), 2.28 (d, J_5-OH,5

875, 820, 775, 700 cm^–1. HRMS (EI, 70 eV): calcd. for C₁₀H₁₇NO₂= 4.7 Hz, 5-OH), 2.64 (d, J_4-OH,4= 5.3 Hz, 4-OH), 3.56 (m_c, 5-H),

183.1259 [M]⁺; found 183.1261 (+0.9 ppm).

4.11 (dddd, J_4,3= J_4,4-OH= J_4,5= 5.2, J_4,2= 1.7 Hz, 4-H), 4.19 (q,

4

J_1Ј,2Ј= 7.1 Hz, 1Ј-H), 6.12 (dd, J_2,3= 15.7, J_2,4= 1.7 Hz, 2-H),

(3E,5E)-Nona-3,5-dien-2-one (14a): Compound 13a (1.80 g,

9.82 mmol) was dissolved in THF (18 mL) and cooled to –20 °C.

MeLi (1.6  in Et₂O, 13.5 mL, 21.6 mmol, 2.2 equiv.) was then

added over 10 min. After 1 h at this temperature the reaction mix-

ture was warmed to 0 °C and stirred for an additional 2 h. The

reaction mixture was then quenched cautiously with satd. aq.

NH₄Cl (10 mL) and the phases were separated. The aq. phase was

extracted with MTBE (3ϫ10 mL) and the combined organic

phases were washed with brine (10 mL) and dried with MgSO₄.

After removal of the solvent under reduced pressure, flash

chromatography (3ϫ17 cm, 20 mL, cyclohexane/EtOAc 40:1) pro-

vided the title compound (fractions 33–57, 1.22 g, 90%) as a

slightly yellow oil. ¹H NMR (400 MHz, C₆D₆/C₆D₅H): δ = 0.74 (t,

6.92 ppm (dd, J_3,2= 15.7 Hz, J_3,4= 5.1 Hz, 3-H). ¹³C NMR

(100 MHz, CDCl₃): δ = 14.02 (C-2Ј), 14.29 (C-8), 18.87 (C-7), 35.26

(C-6), 60.69 (C-1Ј), 73.85 (C-5), 74.26 (C-4), 122.59 (C-2), 146.89

(C-3), 166.41 ppm (C-1). IR (film): ν = 3430, 2960, 2935, 2875,

˜

1705, 1660, 1465, 1395, 1370, 1305, 1275, 1220, 1180, 1130, 1080,

1035, 985, 870, 770 cm^–1. C₁₀H₁₈O₄(202.25): calcd. C 59.39, H

8.97; found C 59.09, H 8.98.

Ethyl (4R,5R,E)-4,5-Dihydroxy-6-methylhept-2-enoate (15b): This

compound was prepared from 12b (2.0 g, 12 mmol) as described for

15a. Flash chromatography (3ϫ16 cm, 20 mL, cyclohexane/EtOAc

4:1) provided the title compound (fractions 25–44, 1.59 g, 66%) as

20

a colorless oil. [α] = +15.5, [α] = +16.8, [α] = +19.0, [α]

589

578

546

436

20

J_9,8= 7.3 Hz, 9-H₃), 1.19 (qt, J_8,9= J_8,7= 7.4 Hz, 8-H₂), 1.80 (tdd,

= +35.2, [α]

= +61.1 (c = 0.61, CHCl₃). The ee (98.0%) was

365

4

J_7,8= J_7.6= 7.2, J_7.5= 1.4 Hz, 7-H₂), 1.89 (s, 1-H₃), 5.67 (dt, J_6,5determined by chiral HPLC [Chiralpak AD-H, n-heptane/EtOH

= 15.0, J_6,7= 7.1 Hz, 6-H), 5.84 (ddtd, J_5,6= 15.2, J_5.4= 10.7, ⁴J_5.7

(80:20), 0.8 mLmin^–1, 215 nm]: t_r(4R,5R)= 16.4 min, t_r(4S,5S)

=

4

= 1.4, J_5.3= 0.7 Hz, 5-H), 5.93 (d, J_3,4= 15.7 Hz, 3-H), 6.91 ppm

10.3 min (determined with racemic material). ¹H NMR (400 MHz,

(ddd, J_4,3= 15.7 Hz, J_4,5= 10.7 Hz, ⁴J_4.6= 0.5 Hz, 4-H). ¹³C NMR

CDCl₃/CHCl₃): δ = 0.92 and 0.93 [2ϫd, J_6-Me,6= 6.8 Hz, 6-

(100 MHz, C₆D₆): δ = 13.66 (C-9), 22.13 (C-8), 27.06 (C-1), 35.14 (CH₃)₂], 1.28 (t, J_2Ј,1Ј= 7.2 Hz, 2Ј-H₃), 1.79 (qqd, J_6,7= J_6,6-Me

(C-7), 129.31 (C-3), 129.44 (C-5), 142.82 (C-6), 144.17 (C-4), 6.7, J_6,5= 5.8 Hz, 6-H), 2.00, (d, J_4-OH,4= 4.9 Hz, 4-OH), 2.37 (d,

=

196.50 ppm (C-2). IR (film): ν = 3325, 2960, 2930, 2875, 1690,

J_5-OH,5= 5.7 Hz, 5-OH), 3.24 (m_c, approximately interpretable as

ddd, J_5,5-OH= 5.2, J_5,4= J_5,6= 4.9 Hz, 5-H), 4.14 (q, J_1Ј,2Ј= 7.1 Hz,

1Ј-H), 4.25 (dddd, J_4,3= J_4,4-OH= J_4,5= 4.9, J_4,2= 1.7 Hz, 4-H),

˜

1635, 1595, 1460, 1435, 1360, 1330, 1310, 1295, 1255, 1185, 1150,

1110, 1045, 1000, 960, 895, 855, 740 cm^–1. HRMS (EI, 70 eV):

calcd. for C₉H₁₄O 138.1045 [M]⁺; found 138.1045 (+0.2 ppm).

4

6.07 (dd, J_2,3= 15.7, J_2,4= 1.7 Hz, 2-H), 6.87 ppm (dd, J_3,2

=

16.0 Hz, J_3,4= 4.9 Hz, 3-H). ¹³C NMR (100 MHz, CDCl₃): δ =

14.30 (C-2Ј), 17.10 and 19.72 [6-(CH₃)₂], 30.10 (C-6), 60.66 (C-2Ј),

71.90 (C-4), 78.75 (C-5), 122.41 (C-2), 147.39 (C-3), 166.39 ppm

(3E,5E)-7-Methylocta-3,5-dien-2-one (14b): This compound was

prepared from 13b (1.45 g, 7.89 mmol) as described for 14a. Flash

chromatography (3ϫ15 cm, 20 mL, cyclohexane/EtOAc 60:1) pro-

vided the title compound (fractions 34–62, 1.08 g, 99%) as a

slightly yellow oil. ¹H NMR (400 MHz, C₆D₆/C₆D₅H): δ = 0.81 (d,

(C-1). IR (film): ν = 3420, 2960, 2875, 1715, 1655, 1465, 1370,

˜

1305, 1275, 1175, 1115, 1090, 1040, 980, 940, 875, 820, 770 cm^–1.

C₁₀H₁₈O₄(202.25): calcd. C 59.39, H 8.97; found C 59.16, H 8.99.

J_8,7and alternatively J_7-Me,7= 6.7 Hz, 8-H₆), 1.90 (s, 1-H₃), 2.06

4

(qqdd, J_7,6= J_7.7-Me= J_7.8= 6.8, J_7.5= 0.6 Hz, 7-H), 5.65 (br. dd, (4R,5R,E)-4,5-Dihydroxy-N-methoxy-N-methyloct-2-enamide (16a):

J_6,5= 15.3, J_6,7= 6.8 Hz, 6-H), 5.83 (dddd, J_5,6= 15.2, J_5,4

=

This compound was prepared from 13a (120 mg, 0.65 mmol) as

Eur. J. Org. Chem. 2010, 4802–4822

www.eurjoc.org

4809

P. Walleser, R. Brückner

FULL PAPER

described for 15a. Flash chromatography (1ϫ10 cm, 4.5 mL, cy-

clohexane/EtOAc 1:1) provided the title compound (fractions 32–

190.1443 [M – NH₄]⁺; found 190.1447 (+2.0 ppm). C₉H₁₆O₃

(172.22): calcd. C 62.77, H 9.36; found C 62.90, H 9.38.

20

55, 82.5 mg, 58%) as a slightly yellow oil. [α] . = –33.8, [α]

=

589

578

20

(5R,6R,E)-5,6-Dihydroxy-7-methyloct-3-en-2-one (17b): This com-

pound was prepared from 14b (738 mg, 5.34 mmol) as described for

15a. Flash chromatography (2ϫ12 cm, 20 mL, cyclohexane/EtOAc

3:1) provided the title compound [fractions 24–42, 506 mg, 55% (in

a 80:20 mixture (w/w) with MeSO₂NH₂, which co-chromato-

graphed with 17b; an analytically pure sample of 17b was obtained

–35.5, [α]

= –40.7, [α]

= –73.3, [α]

= –128.5 (c = 0.87,

546

436

365

CHCl₃). The ee (96.6%) was determined by chiral HPLC [Chi-

ralpak OD-H, n-heptane/EtOH (100:3), 1.0 mLmin^–1, 40 °C iso-

therm, 215 nm]: t_r(4R,5R)= 24.7 min, t_r(4S,5S)= 29.1 min (deter-

mined with racemic material). ¹H NMR (500 MHz, CDCl₃/

CHCl₃): δ = 0.91 (dd, J_8,7-H(A)= J_8,7-H(B)= 6.9 Hz, 8-H₃), 1.30–

1.56 (m, 7-H₂, 6-H₂), 3.11 (br. s, 5-OH), 3.23 (s, NCH₃), 3.37 (br.

s, 4-OH), 3.55 (ddd, J_5,6-H(A)= 8.0, J_5,6-H(B)= J_5,4= 4.6 Hz, 5-H),

3.67 (s, OCH₃), 4.12 (m_c, 4-H), 6.68 (d, J_2,3= 15.4 Hz, 2-H),

6.92 ppm (dd, J_3,2= 15.4 Hz, J_3,4= 5.0 Hz, 3-H). ¹³C NMR

(126 MHz, CDCl₃): δ = 14.04 (C-8), 18.91 (C-7), 32.44 [N(CH)

₃(OCH₃)], 35.18 (C-6), 61.90 [N(CH)₃(OCH₃)], 73.92 (C-4), 74.62

by following the same procedure but in the absence of MeSO₂NH₂;

20

the yield then, however, was only 35%)] as a yellow oil. [α]

=

589

20

+12.9, [α] = +13.3, [α] = +15.3, [α] = +21.8, [α] = +54.5

578

546

436

365

(c = 0.48, CHCl₃). The ee (98.2%) was determined by chiral HPLC

[Chiralpak AD-H, n-heptane/EtOH (70:30), 0.8 mL min^–1, iso-

therm 10 °C, 215 nm]: t_r(5R,6R)= 11.3 min, t_r(5S,6S)= 8.8 min (deter-

mined with racemic material). ¹H NMR (400 MHz, CDCl₃/

CHCl₃): δ = 0.92 and 0.93 [2ϫd, J_7-Me,7= 6.8 Hz, 7-(CH₃)₂], 1.78

(qqd, J_7,8= J_7,7-Me= 6.8, J_7,6= 5.9 Hz, 7-H), 2.40, (br. s, 6-OH),

(C-5), 119.61 (C-2), 146.20 (C-3), 166.59 ppm (C-1). IR (film): ν =

˜

3400, 2960, 2935, 2875, 1660, 1620, 1425, 1385, 1180, 1080, 1000,

850 cm^–1. C₁₀H₁₉NO₄(217.26): calcd. C 55.28, H 8.81, N 6.45;

found C 55.13, H 9.01, N 6.25.

2.81 (br. s, 5-OH), 3.24 (m_c, 6-H), 4.27 (m_c, 5-H), 6.30 (dd, J_3,4

=

4

16.0, J_3,5= 1.6 Hz, 3-H), 6.71 ppm (dd, J_4,3= 16.0, J_4,5= 5.1 Hz,

4-H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.24 and 19.69 [7-(CH₃)

₂], 27.67 (C-7), 30.23 (C-1), 71.90 (C-5), 78.81 (C-6), 130.75 (C-3),

(4R,5R,E)-4,5-Dihydroxy-N-methoxy-N,6-dimethylhept-2-enamide

(16b): This compound was prepared from 13b (100 mg, 0.55 mmol)

as described for 15a. Flash chromatography (1ϫ11 cm, 4.5 mL,

cyclohexane/EtOAc 1:1) provided the title compound (fractions 20–

146.48 (C-4), 198.66 ppm (C-2). IR (film): ν = 3395, 2960, 2930,

˜

2875, 1675, 1635, 1505, 1465, 1425, 1360, 1260, 1175, 1140, 1120,

1090, 1045, 1010, 980, 945, 805, 725 cm^–1. HRMS (Cl, NH₃): calcd.

for C₉H₂₀NO₃190.1443 [M – NH₄]⁺; found 190.1445 (+1.0 ppm).

C₉H₁₆O₃(172.22): calcd. C 62.77, H 9.36; found C 62.61, H 9.55.

20

42, 100 mg, 84%) as a slightly yellow oil. [α] = +17.9, [α]

=

589

578

20

+18.7, [α]

= +21.6, [α]

= +39.6, [α]

= +69.8 (c = 0.94,

546

536

365

CHCl₃). The ee (98.9%) was determined by chiral HPLC [Chi-

ralpak AD-H, n-heptane/EtOH (90:10), 0.8 mLmin^–1, 215 nm]:

t_r(4R,5R)= 34.7 min, t_r(4S,5S)= 25.5 min (determined with racemic

(E)-4-[(4R,5R)-2-Phenyl-5-propyl-1,3,2-dioxaborolan-4-yl]-but-3-en-

2-one (18): Compound 17a (205 mg, 1.19 mmol) and phenylboronic

acid (176 mg, 1.43 mmol, 1.2 equiv.) were dissolved in CH₂Cl₂

(7 mL) and stirred at room temp. for 24 h. The solvent was removed

under reduced pressure and flash chromatography (1.5ϫ18 cm,

10 mL, cyclohexane/EtOAc 10:1) provided the title compound

(fractions 12–30, 316 mg, 85%) as a colorless oil. [α]₅²₈⁰₉= –47.9, [α]

1

material). H NMR (400 MHz, CDCl₃/CHCl₃): δ = 0.97 and 0.97

[2ϫd, J_6-Me,6= 6.8 Hz, 6-(CH₃)₂], 1.85 (qqd, J_6,7= J_6,6-Me= 6.8,

J_6,5= 5.8 Hz, 6-H), 2.88 (d, J_5-OH,5= 4.8 Hz, 5-OH), 3.13 (d, J_4-

= 6.3 Hz, 4-OH), 3.70 (s, NCH₃), 3.29 (ddd, J_5,6= 5.5, J_5,4

=

OH,4

J_5,5-OH= 5.0 Hz, 5-H), 3.70 (s, OCH₃), 4.32 (dddd, J_4,4-OH= 6.3,

4

J_4,5= J_4,3= 4.8, J_4,2= 1.6 Hz, 4-H), 6.69 (dd, J_2,3= 15.6, J_2,4

=

1.2 Hz, 2-H), 6.93 ppm (dd, J_3,2= 15.3 Hz, J_3,4Ј= 4.9 Hz, 3-H).

¹³C NMR (100 MHz, CDCl₃): δ = 17.25 and 19.74 [6-(CH₃)₂],

30.03 (C-6), 32.45 [N(CH₃)(OCH₃)], 61.90 [N(CH₃)(OCH₃)], 72.27

(C-4), 78.82 (C-5), 119.46 (C-2), 146.68 (C-3), 166.62 ppm (C-1).

20

= –50.5, [α]

= –58.7, [α]

= –113.3, [α]

= –192.1 (c =

578

546

436

365

1

0.70, CHCl₃). H NMR (400 MHz, CDCl₃/CHCl₃): δ = 1.10 (dd,

J_{3ЈЈ,2ЈЈ-H(A)}= J_{3ЈЈ,2ЈЈ-H(B)}= 7.3 Hz, 3ЈЈ-H₃), 1.51–1.73 (m, 2ЈЈ-H₂),

AB signal (δ_A= 1.78, δ_B= 1.86, J_AB= 13.4, A part additionally

split by J_A,2ЈЈ-H(A)= 9.8, J_A,2ЈЈ-H(B)= 5.9, J_A,5= 5.3 Hz, B part

IR (film): ν = 3385, 2960, 1735, 1720, 1685, 1660, 1615, 1425, 1385,

˜

1245, 1180, 1145, 1125, 1085, 995 cm^–1. C₁₀H₁₉NO₄(217.26): calcd.

C 55.28, H 8.81, N 6.45; found C 55.19, H 9.09, N 6.23.

additionally split by J_B,2ЈЈ-H(B)= 10.1 Hz, J_B,5= 7.4 Hz, J_B,2ЈЈ-H(A)

4

= 5.5 Hz, 1ЈЈ-H₂), 2.39 (d, J_1,3= 0.4 Hz, 1-H₃), 4.36 (ddd, J_5Ј,4Ј

=

(5R,6R,E)-5,6-Dihydroxynon-3-en-2-one (17a): This compound was

prepared from 14a (800 mg, 5.79 mmol) as described for 15a. Flash

chromatography (2ϫ14 cm, 20 mL, cyclohexane/EtOAc 3:1) pro-

vided the title compound [fractions 28–52, 518 mg, 52% (in a 78:22

mixture (w/w) with MeSO₂NH₂, which co-chromatographed with

17a. An analytically pure sample of 17a was obtained by following

J_{5Ј,1ЈЈ-H(B)}= 7.1, J_{5Ј,1ЈЈ-H(A)}= 5.3 Hz, 5Ј-H), 4.82 (m_c, approximately

4

interpretable as ddd, J_4Ј,5Ј= 6.9, J_4Ј,4= 5.3, J_4Ј,3= 1.6 Hz, 4Ј-H),

4

6.48 (dd, J_3,4= 15.9, J_3,4Ј= 1.5 Hz, 3-H), 6.88 (ddd, J_4,3= 15.9,

4

J_4,4Ј= 5.2, J_4,1= 0.5 Hz, 4-H), 7.49 (m_c, 2ϫ meta-H), 7.59 (m_c,

para-H), 7.94 ppm (m_c, 2 ϫ ortho-H). ¹³C NMR (100 MHz,

CDCl₃): δ = 13.99 (C-3ЈЈ), 18.43 (C-2ЈЈ), 27.86 (C-1), 38.00 (C-1ЈЈ),

81.66 (C-5Ј), 82.41 (C-4Ј), 127.98 (2ϫ meta-C, para-C), 130.13 (C-

3), 131.83 (ipso-C), 135.01 (2ϫ ortho-C), 143.89 (C-4), 197.88 ppm

the same procedure but in the absence of MeSO₂NH₂; the yield

20

then, however, was only 44%)] as a yellow oil. [α] = +35.4, [α]

589

20

= +37.1, [α] = +42.6, [α] = +73.0 (c = 0.96, CHCl₃). The

(C-2). IR (film): ν = 3395, 3080, 3055, 3025, 2960, 2935, 2875,

˜

578

546

436

ee (97.2%) was determined by chiral HPLC [Chiralpak AD-H, n-

heptane/EtOH (80:20), 0.8 mLmin^–1, 215 nm]: t_r(5R,6R)= 12.4 min,

t_r(5S,6S)= 9.7 min (determined with racemic material). ¹H NMR

1700, 1680, 1635, 1605, 1500, 1440, 1405, 1360, 1320, 1255, 1235,

1210, 1175, 1115, 1095, 1070, 1030, 985, 945, 890, 850, 800,

770 cm^–1. C₁₅H₁₉BO₃(258.12): calcd. C 69.8, H 7.42; found C

69.59, H 7.31.

(400 MHz, CDCl₃/CHCl₃): δ = 0.94 (dd, J_9,8-H(A)= J_9,8-H(B)

=

6.8 Hz, 9-H₃), 1.33–1.57 (m, 7-H₂, 8-H₂), 2.28 (s, 1-H₃), 2.78 (d, J_6-

= 4.9 Hz, 6-OH), 3.22 (d, J_5-OH,5= 5.3 Hz, 5-OH), 3.58 (m_c,

Ethyl (E)-3-[(4R,5R)-2-Oxo-5-propyl-1,3-dioxolan-4-yl]acrylate

(23a): Compound 17a (366 mg, 1.81 mmol) and pyridine (0.73 mL,

0.72 g, 9.10 mmol, 5.0 equiv.) were dissolved in CH₂Cl₂(5 mL) and

the mixture was cooled to 0 °C. A solution of triphosgene (590 mg,

OH,6

4

6-H), 4.14 (dddd, J_5,4= J_5,6= J_5,5-OH= 5.2, J_5,3= 1.6 Hz, 5-H),

4

6.35 (dd, J_3,4= 15.9, J_3,5= 1.6 Hz, 3-H), 6.78 ppm (dd, J_4,3

=

15.9 Hz, J_4,5= 5.1 Hz, 4-H). ¹³C NMR (100 MHz, CDCl₃): δ =

14.01 (C-9), 18.88 (C-8), 27.62 (C-1), 35.33 (C-7), 73.84 (C-5), 74.25 1.99 mmol, 1.1 equiv.) in CH₂Cl₂(10 mL) was then slowly added.

(C-6), 130.90 (C-3), 146.13 (C-4), 198.87 ppm (C-2). IR (film): ν = The reaction was stirred for 1.5 h and quenched cautiously with

˜

3395, 2960, 2870, 1675, 1635, 1505, 1465, 1425, 1365, 1260, 1120,

satd. aq. NH₄Cl (10 mL). The phases were separated and the aq.

phase was extracted with MTBE (3ϫ10 mL). The combined or-

1075, 1025, 980 cm^–1. HRMS (Cl, NH₃): calcd. for C₉H₂₀NO₃

4810

www.eurjoc.org

Eur. J. Org. Chem. 2010, 4802–4822

1,3,5-Triols by Asymmetric Dihydroxylation and Deoxygenation

ganic phases were washed with satd. aq. NaHCO₃(10 mL) and

brine (10 mL) and dried with MgSO₄. After removal of the solvent

under reduced pressure, flash chromatography (2ϫ18 cm, 10 mL,

cyclohexane/EtOAc 3:1) provided the title compound (fractions 8–

= 4.7 Hz, 3-H). ¹³C NMR (100 MHz, CDCl₃): δ = 13.68 (C-3ЈЈ),

18.15 (C-2ЈЈ), 32.45 [N(CH₃)(OCH₃)], 35.33 (C-1ЈЈ), 62.14

[N(CH₃)(OCH₃)], 80.43 (C-5Ј), 81.60 (C-4Ј), 122.09 (C-2), 137.91

(C-3), 153.94 (C-2Ј), 164.87 ppm (C-1). IR (film): ν = 3445, 2960,

˜

20

19, 356 mg, 88%) as a slightly yellow oil. [α] = +42.4, [α]

=

2940, 2875, 1805, 1670, 1635, 1460, 1420, 1380, 1310, 1220, 1180,

1120, 1085, 1060, 1035, 995, 770 cm^–1. C₁₁H₁₇NO₅(243.26): calcd.

C 54.31, H 7.04; found C 54.10, H 7.03.

589

578

20

+44.0, [α]

= +50.0, [α]

= +83.2, [α]

= +127.4 (c = 0.51,

546

436

365

CHCl₃). ¹H NMR (400 MHz, CDCl₃/CHCl₃): δ = 0.97 (dd, J_{3ЈЈЈ,2ЈЈЈ-}

_H(A)= J_{3ЈЈЈ,2ЈЈЈ-H(B)}= 7.4 Hz, 3ЈЈЈ-H₃), 1.29 (t, J_2Ј,1Ј= 7.1 Hz, 2Ј-

H₃), AB signal (δ_A= 1.44, δ_B= 1.53, J_AB= 13.3 Hz, A part ad-

ditionally split by J_{A,1ЈЈЈ-H(A)}= 9.7 Hz, J_A,3ЈЈЈ= 7.2 Hz, J_{A,1ЈЈЈ-H(B)}

(E)-3-[(4R,5R)-5-Isopropyl-2-oxo-1,3-dioxolan-4-yl]-N-methoxy-N-

methylacrylamide (24b): This compound was prepared from 16b

(2.66 g, 12.2 mmol) as described for 23a. Flash chromatography

(3ϫ15 cm, 20 mL, cyclohexane/EtOAc 3:1) provided the title com-

pound (fractions 32–55, 2.32 mg, 78%) as a slightly yellow oil.

= 6.2 Hz, B part additionally split by J_{B,1ЈЈЈ-H(B)}= 9.4 Hz, J_B,3ЈЈЈ

7.5 Hz, J_{B,1ЈЈЈ-H(A)}= 5.6 Hz, 2ЈЈЈ-H₂), AB signal (δ_A= 1.70, δ_B

1.80, J_AB= 14.1 Hz, A part additionally split by J_{A,2ЈЈЈ-H(A)}

=

20

[α]

= +51.6, [α]

= +54.0, [α]

= +61.5, [α]

= +106.7,

589

578

546

436

9.5 Hz, J_A,5ЈЈ= 8.1 Hz, J_{A,2ЈЈЈ-H(B)}= 5.7 Hz, B part additionally

split by J_{B,2ЈЈЈ-H(B)}= 9.5 Hz, J_{B,2ЈЈЈ-H(A)}= 6.1 Hz, J_B,5ЈЈ= 4.8 Hz,

= +175.2 (c = 0.93, CHCl₃). ¹H NMR (400 MHz, CDCl₃/

20

365

CHCl₃): δ = 1.01 and 1.05 [2ϫd, J_{1ЈЈ-Me,1ЈЈ}= 6.7 Hz, 1ЈЈ-(CH₃)₂],

2.01 (qqd, J_1ЈЈ,2ЈЈ= J_{1ЈЈ,1ЈЈ-Me}= J_1ЈЈ,5Ј= 6.6 Hz, 1ЈЈ-H), 3.26 (s,

1ЈЈЈ-H₂), 4.21 (q, J_1Ј,2Ј= 7.2 Hz, 2Ј-H₃), 4.35 (ddd, J_{5ЈЈ,1ЈЈЈ-H(A)}

7.8, J_5ЈЈ,4ЈЈ= 7.2, J_{5ЈЈ,1ЈЈЈ-H(B)}= 5.0 Hz, 5ЈЈ-H), 4.80 (ddd, J_4ЈЈ,5ЈЈ

=

NCH₃), 3.71 (s, OCH₃), 4.13 (dd, J_5Ј,1Ј= J_5Ј,4Ј= 6.6 Hz, 5Ј-H), 4.96

4

7.2, J_4ЈЈ,3= 5.7, J_4ЈЈ,2= 1.5 Hz, 4ЈЈ-H), 6.16 (dd, J_2,3= 15.7, J_2,4ЈЈ

= 1.5 Hz, 2-H), 6.82 ppm (dd, J_3,2= 15.7 Hz, J_3,4ЈЈ= 5.7 Hz, 3-H).

¹³C NMR (100 MHz, CDCl₃): δ = 13.62 (C-3ЈЈЈ), 14.18 (C-2Ј),

18.08 (C-2ЈЈЈ), 35.28 (C-1ЈЈЈ), 61.18 (C-1Ј), 79.92 (C-5ЈЈ), 81.26 (C-

4ЈЈ), 125.00 (C-3), 139.35 (C-2), 153.68 (C-2ЈЈ), 164.97 ppm (C-1).

4

(ddd, J_4Ј,5Ј= 6.7, J_4Ј,3= 4.5, J_4Ј,2= 1.1 Hz, 4Ј-H), 6.76 (d, J_2,3

=

15.8 Hz, 2-H), 6.84 ppm (dd, J_3,2= 15.4 Hz, J_3,4Ј= 4.5 Hz, 3-H).

¹³C NMR (100 MHz, CDCl₃): δ = 17.12 and 17.27 [(CH₃)_2–1ЈЈ],

31.72 (C-1ЈЈ), 32.42 [N(CH₃)(OCH₃)], 62.11 [N(CH₃)(OCH₃)],

78.11 (C-5Ј), 85.97 (C-4Ј), 121.64 (C-2), 138.97 (C-3), 153.92 (C-

IR (film): ν = 3430, 2965, 2940, 2875, 1810, 1725, 1665, 1510, 1465,

˜

2Ј), 164.90 ppm (C-1). IR (film): ν = 2965, 2940, 2880, 1810, 1670,

˜

1370, 1305, 1275, 1180, 1090, 1035, 980, 870, 770 cm^–1. C₁₁H₁₆O₅

(228.24): calcd. C 57.88, H 7.07; found C 57.77, H 7.21.

1640, 1465, 1425, 1385, 1275, 1170, 1125, 1050, 995, 770 cm^–1

.

C₁₁H₁₇NO₅(243.26): calcd. C 54.31, H 7.04; found C 54.10, H

7.14.

Ethyl (E)-3-[(4R,5R)-5-Isopropyl-2-oxo-1,3-dioxolan-4-yl]acrylate

(23b): This compound was prepared from 15b (934 mg, 4.62 mmol)

as described for 23a. Flash chromatography (1.5ϫ15 cm, 5 mL,

cyclohexane/EtOAc 6:1) provided the title compound (fractions 10–

(4R,5R)-4-[(E)-3-Oxobut-1-enyl]-5-propyl-1,3-dioxolan-2-one (25a):

This compound was prepared from 17a (4.04 g, 23.5 mmol) as de-

scribed for 23a. Flash chromatography (4.5ϫ18 cm, 50 mL, cyclo-

hexane/EtOAc 4:1) provided the title compound (fractions 8–25,

20

18, 822 mg, 78%) as a slightly yellow oil. [α] = +33.0, [α]

=

589

578

20

+34.7, [α]

= +39.3, [α]

= +64.8, [α]

= +98.4 (c = 0.45,

20

546

436

365

4.43 g, 95%) as a slightly yellow oil. [α] = +44.7, [α] = +46.7,

589

578

CHCl₃). ¹H NMR (400 MHz, CDCl₃/CHCl₃): δ = 1.01 and 1.05

[2ϫd, J_{1ЈЈЈ-Me,1ЈЈЈ}= 6.8 Hz, 1ЈЈЈ-(CH₃)₂], 1.30 (t, J_2Ј,1Ј= 7.1 Hz, 2Ј-

H₃), 2.01 (qqd, J_{1ЈЈЈ,2ЈЈЈ}= J_{1ЈЈЈ,1ЈЈЈ-Me}= J_{1ЈЈЈ,5ЈЈ}= 6.8 Hz, 1ЈЈЈ-H), 4.13

(dd, J_5ЈЈ,4ЈЈ= J_5ЈЈ,1ЈЈ= 6.6 Hz, 5ЈЈ-H), 4.22 (q, J_1Ј,2Ј= 7.1 Hz, 1Ј-

20

[α] = +53.1, [α] = +92.7, [α] = +181.8 (c = 0.64, CHCl₃).

546

436

365

¹H NMR (400 MHz, CDCl₃/CHCl₃): δ = 0.98 (dd, J_3Ј,2Ј-H(A)

J_3Ј,2Ј-H(B)= 7.3 Hz, 3Ј-H₃), AB signal (δ_A= 1.45, δ_B= 1.54, J_AB

13.3 Hz, A part additionally split by J_A,1Ј-H(A)= 9.8 Hz, J_A,3Ј

7.2 Hz, J_A,1Ј-H(B)= 6.2 Hz, B part additionally split by J_B,1Ј-H(B)

9.5 Hz, J_B,3Ј= 7.5 Hz, J_B,1Ј-H(A)= 5.6 Hz, 2Ј-H₂), AB signal (δ_A

=

4

H₂), 4.91 (ddd, J_4ЈЈ,5ЈЈ= 6.6, J_4ЈЈ,3= 5.4, J_4ЈЈ,2= 1.3 Hz, 4ЈЈ-H),

4

6.18 (dd, J_2,3= 15.7, J_2,4ЈЈ= 1.5 Hz, 2-H), 6.82 ppm (dd, J_3,2

=

15.7 Hz, J_3,4ЈЈ= 5.4 Hz, 3-H). ¹³C NMR (100 MHz, CDCl₃): δ =

14.21 (C-1Ј), 17.13 and 17.22 [1ЈЈЈ-(CH₃)₂], 31.74 (C-1ЈЈЈ), 61.20 (C-

1Ј), 77.63 (C-4ЈЈ), 85.74 (C-5ЈЈ), 124.61 (C-3), 140.35 (C-2), 153.92

1.72, δ_B= 1.82, J_AB= 14.1 Hz, A part additionally split by

J_A,2Ј-H(A)= 9.8 Hz, J_A,5= 8.0 Hz, J_A,2Ј-H(B)= 5.5 Hz, B part ad-

ditionally split by J_B,2Ј-H(B)= 9.6 Hz, J_B,2Ј-H(B)= 6.1 Hz, J_B,5

4.8 Hz, 1Ј-H₂), 2.31 (s, 4ЈЈ-H₃), 4.37 (ddd, J_5,1Ј-H(A)= 7.9, J_5,4

=

(C-2ЈЈ), 165.08 ppm (C-1). IR (film): ν = 3425, 2970, 2935, 2880,

˜

1810, 1720, 1665, 1465, 1395, 1365, 1310, 1280, 1250, 1185, 1095,

1055, 980 cm^–1. C₁₁H₁₆O₅(228.24): calcd. C 57.88, H 7.07; found

C 57.73, H 7.06.

7.1, J_5,1Ј-H(B)= 4.9 Hz, 5-H), 4.82 (ddd, J_4,5= 7.1, J_4,1ЈЈ= 5.6, ⁴J_4,2ЈЈ

4

= 1.4 Hz, 4-H), 6.41 (dd, J_2ЈЈ,1ЈЈ= 15.9, J_2ЈЈ,4= 1.4 Hz, 2ЈЈ-H),

6.65 ppm (dd, J_1ЈЈ,2ЈЈ= 15.9 Hz, J_1ЈЈ,4= 5.6 Hz, 1ЈЈ-H). ¹³C NMR

(100 MHz, CDCl₃): δ = 13.64 (C-3Ј), 18.10 (C-2Ј), 28.37 (C-4ЈЈ),

35.35 (C-1Ј), 80.09 (C-5), 81.35 (C-4), 132.15 (C-2ЈЈ), 137.53 (C-

(E)-3-[(4R,5R)-2-Oxo-5-propyl-1,3-dioxolan-4-yl]-N-methoxy-N-

methylacrylamide (24a): This compound was prepared from 16a

(534 mg, 2.46 mmol) as described for 23a. Flash chromatography

(2ϫ14 cm, 20 mL, cyclohexane/EtOAc 3:1) provided the title com-

pound (fractions 17–38, 430 mg, 72 %) as a slightly yellow oil.

1ЈЈ), 153.68 (C-2), 196.65 ppm (C-3ЈЈ). IR (film): ν = 3580, 2965,

˜

2940, 2875, 1810, 1705, 1680, 1640, 1545, 1465, 1430, 1365, 1305,

1255, 1225, 1180, 1120, 1085, 1055, 1035, 980, 895, 775, 750,

720 cm^–1. C₁₀H₁₄O₄(198.22): calcd. C 60.59, H 7.12; found C

60.49, H 7.08.

20

[α]

= +56.5, [α]

= +58.9, [α]

= +67.1, [α]

= +115.4,

589

578

546

436

= +186.4 (c = 0.68, CHCl₃). ¹H NMR (400 MHz, CDCl₃/

20

365

CHCl₃): δ = 0.99 (dd, J_{3ЈЈ,2ЈЈ-H(A)}= J_{3ЈЈ,2ЈЈ-H(B)}= 7.4 Hz, 3ЈЈ-H₃), (4R,5R)-4-Isopropyl-5-[(E)-3-oxobut-1-enyl]-1,3-dioxolan-2-one

AB signal (δ_A= 1.45, δ_B= 1.56, J_AB= 13.3 Hz, A part additionally

split by J_A,1ЈЈ-H(A)= 9.8 Hz, J_A,3ЈЈ= 7.2 Hz, J_A,1ЈЈ-H(B)= 6.3 Hz, B

part additionally split by J_B,1ЈЈ-H(B)= 9.5 Hz, J_B,3ЈЈ= 7.6 Hz, J_B,1ЈЈ-

(25b): This compound was prepared from 17b (192 mg, 11.1 mmol)

as described for 23a. Flash chromatography (1.5ϫ16 cm, 5 mL,

cyclohexane/EtOAc 4:1) provided the title compound (fractions 20–

20

= 5.7 Hz, 2ЈЈ-H₂), AB signal (δ_A= 1.73, δ_B= 1.82, J_AB

=

38, 183 mg, 83%) as a slightly yellow oil. [α] = +11.2, [α]

=

H(A)

589

578

20

14.1 Hz, A part additionally split by J_A,2ЈЈ-H(A)= 9.8 Hz, J_A,5Ј

8.0 Hz, J_A,2ЈЈ-H(B)= 5.5 Hz, B part additionally split by J_B,2ЈЈ-H(B)

+11.3, [α]

= +12.6, [α]

= +16.3, [α]

= +24.2 (c = 0.97,

546

436

365

CHCl₃). ¹H NMR (400 MHz, CDCl₃/CHCl₃): δ = 1.01 and 1.05

9.5 Hz, J_B,2ЈЈ-H(A)= 6.1 Hz, J_B,5Ј= 4.8 Hz, 1ЈЈ-H₂), 3.26 (s, NCH₃), [2ϫd, J_1Ј-Me,1Ј= 6.8 Hz, 1Ј-(CH₃)₂], 2.01 (qqd, J_1Ј,2Ј= J_1Ј,1Ј-Me

=

3.72 (s, OCH₃), 4.37 (ddd, J_{5Ј,1ЈЈ-H(A)}= J_5Ј,4Ј= 7.6, J_{5Ј,1ЈЈ-H(B)}

=

J_1Ј,5= 6.7 Hz, 1Ј-H), 2.30 (s, 4ЈЈ-H₃), 4.14 (dd, J_5,4= J_5,1Ј= 6.5 Hz,

4

5.0 Hz, 5Ј-H), 4.86 (ddd, J_4Ј,5Ј= 7.4, J_4Ј,3= 4.7, ⁴J_4,2Ј= 1.1 Hz, 4Ј-

5-H), 4.92 (ddd, J_4,5= 6.5, J_4,1ЈЈ= 5.2, J_4,2ЈЈ= 1.3 Hz, 4-H), 6.42

4

H), 6.78 (d, J_2,3= 15.8 Hz, 2-H), 6.85 ppm (dd, J_3,2= 15.4 Hz, J_3,4Ј(dd, J_2ЈЈ,1ЈЈ= 15.9, J_2ЈЈ,4= 1.5 Hz, 2ЈЈ-H), 6.65 ppm (dd, J_1ЈЈ,2ЈЈ

=

Eur. J. Org. Chem. 2010, 4802–4822

www.eurjoc.org

4811

P. Walleser, R. Brückner

FULL PAPER

15.9 Hz, J_1Ј,4= 5.4 Hz, 1ЈЈ-H). ¹³C NMR (100 MHz, CDCl₃): δ =

5 mL, cyclohexane/EtOAc 1:1) provided the title compound (frac-

17.13 and 17.18 [1Ј-(CH₃)₂], 28.48 (C-4ЈЈ), 31.75 (C-1Ј), 77.78 (C- tions 22–36, 20 mg, 30%) as a slightly yellow oil. Compound 27a

4), 85.80 (C-5), 131.67 (C-2ЈЈ), 38.50 (C-1ЈЈ), 153.70 (C-2),

198.69 ppm (C-2ЈЈ). IR (film): ν = 3390, 2970, 2880, 1800, 1685,

(major isomer): ¹H NMR (400 MHz, CDCl₃/CHCl₃): δ = 0.93 (dd,

J_8,7-H(A)= J_8,7-H(B)= 6.9 Hz, 8-H₃), 1.30–1.53 (m, 6-H₂, 7-H₂), 1.64

(br. s, 5-OH), AB signal (δ_A= 2.36, δ_B= 2.44, J_AB= 14.1 Hz, A

˜

1640, 1470, 1425, 1365, 1310, 1255, 1170, 1055, 980, 770 cm^–1

.

4

C₁₀H₁₄O₄(198.22): calcd. C 60.59, H 7.12; found C 60.30, H 7.23.

part additionally split by J_A,3= J_A,5= 7.7 Hz, J_A,2= 1.3 Hz, B

4

part additionally split by J_B,3= 7.2 Hz, J_B,5= 4.7 Hz, J_B,2

=

Ethyl (R,E)-5-Hydroxyoct-2-enoate [26a; as a mixture (97:3) with

ethyl (R,E)-5-hydroxyoct-3-enoate (iso-26a)]: Pd₂(dba)₃·CHCl₃

(0.11 g, 0.11 mmol, 2.5 mol-%) and PPh₃(73 mg, 0.28 mmol,

6.3 mol-%) were dissolved in THF (25 mL) and stirred at room

temp. for 30 min. Compound 23a (998 mg, 4.37 mmol) in THF

(5 mL), triethylamine (1.85 mL, 1.33 g, 13.1 mmol, 3.0 equiv.) and

formic acid (0.50 mL, 0.60 g, 13 mmol, 3.0 equiv.) were then suc-

cessively added and the system was heated at reflux for 2 h. The

reaction mixture was allowed to cool to room temp. and quenched

with satd. aq. NaHCO₃(20 mL). The phases were separated. The

aq. phase was extracted with EtOAc (3ϫ20 mL). The combined

organic phases were washed with brine (20 mL) and dried with

MgSO₄. After removal of the solvent under reduced pressure, flash

chromatography (3.5ϫ18 cm, 20 mL, cyclohexane/EtOAc 10:1)

provided the title compound (fractions 46–75, 578 mg, 71%) as a

yellow oil. Compound 26a (major isomer): ¹H NMR (400 MHz,

CDCl₃/CDCl₃): δ = 0.93 (dd, J_8,7-H(A)= J_8,7-H(B)= 6.9 Hz, 8-H₃),

1.28 (t, J_2Ј,1Ј= 7.1 Hz, 2Ј-H₂), 1.30–1.52 (m, 6-H₂, 7-H₂), 1.61 (br.

s, 5-OH), AB signal (δ_A= 2.32, δ_B= 2.40, J_AB= 14.4 Hz, A part

1.6 Hz, 4-H₂), 3.24 (s, NCH₃), 3.70 (s, OCH₃), 3.78 (m_c, 5-H), 6.49

(ddd, J_2,3= 15.4, J_2,4-H(A)

(ddd, J_3,2= 15.3 Hz, J_3,4–H(A)= 8.0 Hz, J_3,4–H(B)= 7.2 Hz, 3-H).

¹³C NMR (100 MHz, CDCl₃): δ = 14.08 (C-8), 18.90 (C-7), 32.44

[N(CH₃)(OCH₃)], 39.27 (C-6), 40.69 (C-4), 61.81 [N(CH₃)(OCH₃)],

70.44 (C-5), 121.60 (C-2), 143.62 (C-3), 166.66 ppm (C-1). IR

4

=

⁴J_2,4-H(B)= 1.3 Hz, 2-H), 6.98 ppm

(film): ν = 3410, 2960, 2935, 2875, 1660, 1625, 1460, 1420, 1385,

˜

1180, 1120, 1000 cm^–1. HRMS (CI, NH₃): calcd. for C₁₀H₂₀NO₃

202.1442 [M + H]⁺; found 202.1443 (+0.1 ppm).

(S,E)-5-Hydroxy-N-methoxy-N,6-dimethylhept-2-enamide [27b; as a

mixture (89:11) with (R,E)-5-hydroxy-N-methoxy-N,6-dimethylhept-

3-enamide (iso-27b)]: This compound was prepared from 24b

(78 mg, 0.32 mmol) as described for 26a. Flash chromatography

(1ϫ11 cm, 5 mL, cyclohexane/EtOAc 1:1) provided the title com-

pound (fractions 14–36, 42 mg, 65%) as a slightly yellow oil. Com-

20

pound 27b (major isomer): [α] = –11.3, [α] = –13.1, [α] =

578

546

436

20

–22.7, [α]

= –31.4 (c = 0.60, CHCl₃). ¹H NMR (300 MHz,

365

CDCl₃/CHCl₃): δ = 0.92 (d, J_7,6and alternatively J_6-Me,6= 6.7 Hz,

7-H₆), 1.69 (m_c, 6-H), 2.12 (br. s, 5-OH), AB signal (δ_A= 2.32, δ_B

additionally split by J_A,3= 7.7 Hz, J_A,5= 7.2 Hz, ⁴J_A,2= 1.3 Hz, B

4

part additionally split by J_B,3= 7.3 Hz, J_B,5= 4.6 Hz, J_B,2

=

= 2.42, J_AB= 14.1 Hz, A part additionally split by J_A,5= J_A,3=

4

1.6 Hz, 4-H₂), 3.77 (m_c, 5-H), 4.18 (q, J_1Ј,2Ј= 7.1 Hz, 1Ј-H), 5.90 8.1 Hz, J_A,2= 1.1 Hz, B part additionally split by J_B,3= 8.1 Hz,

(ddd, J_2,3= 15.6 Hz, ⁴J_2,4-H(A)= ⁴J_2,4-H(B)= 1.5 Hz, 2-H), 6.97 ppm

(ddd, J_3,2= 15.6 Hz, J_3,4–H(A)= J_3,4–H(B)= 7.4 Hz, 3-H). ¹³C NMR

(100 MHz, CDCl₃): δ = 14.03 (C-2Ј), 14.33 (C-8), 18.85 (C-7), 39.35

J_B,5= 4.1 Hz, J_B,2= 1.5 Hz, 4-H₂), 3.19 (s, NCH₃), 3.49 (m_c, 5-

H), 3.67 (s, OCH₃), 6.46 (br. d, J_2,3= 15.4 Hz, 2-H), 6.97 ppm

(ddd, J_3,2= 15.2 Hz, J_3,4–H(A)= J_3,4–H(B)= 7.9 Hz, 3-H). ¹³C NMR

4

(C-6), 40.28 (C-4), 60.37 (C-1Ј), 70.37 (C-5), 123.96 (C-2), 145.26 (100 MHz, CDCl₃): δ = 17.34 and 18.86 [6-(CH₃)₂], 32.45

(C-3), 166.42 ppm (C-1). IR (film): ν = 3430, 2960, 2935, 2875, [N(CH₃)(OCH₃)], 33.40 (C-6), 37.65 (C-4), 61.81 [N(CH₃)(OCH₃)],

˜

1720, 1655, 1465, 1395, 1370, 1320, 1270, 1210, 1170, 1125, 1095,

1045, 985, 850, 750 cm^–1. HRMS (EI, 70 eV): calcd. for C₈H₁₃O₂

141.0916 [M – OCH₂CH₃]⁺; found 141.0912 (–2.5 ppm).

75.38 (C-5), 121.42 (C-2), 144.25 (C-3), 166.68 ppm (C-1). IR

(film): ν = 3430, 2960, 2895, 2875, 1660, 1625, 1465, 1420, 1385,

˜

1295, 1180, 1150, 1120, 1045, 995 cm^–1. HRMS (CI, NH₃): calcd.

for C₁₀H₂₀NO₃202.1443 [M + H]⁺; found 202.1439 (+2.1 ppm).

Ethyl (S,E)-5-Hydroxy-6-methylhept-2-enoate [26b; as a mixture

(96:4) with ethyl (R,E)-5-hydroxy-6-methylhept-2-enoate (iso-26b)]:

This compound was prepared from 23b (513 mg, 2.23 mmol) as

described for 26a. Flash chromatography (3ϫ16 cm, 20 mL, cyclo-

hexane/EtOAc 10:1) provided the title compound (fractions 44–65,

306 mg, 73%) as a yellow oil. Compound 26b (major isomer): [α]

(R,E)-6-Hydroxynon-3-en-2-one [28a; as a mixture (89:11) with

(R,E)-6-hydroxynon-4-en-2-one (iso-28a)]: This compound was pre-

pared from 25a (82 mg, 0.41 mmol) as described for 26a. Flash

chromatography (1ϫ16 cm, 5 mL, cyclohexane/EtOAc 5:1) pro-

vided the title compound (fractions 34–45, 47 mg, 72%) as a yellow

20

1

= –17.2, [α] = –18.4, [α] = –20.9, [α] = –37.8 (c = 0.64,

oil. Compound 28a (major isomer): H NMR (400 MHz, CDCl₃/

589

578

546

436

CHCl₃). ¹H NMR (400 MHz, CDCl₃/CDCl₃): δ = 0.93 and 0.94

CHCl₃): δ = 0.93 (dd, J_9,8-H(A)= J_9,8-H(B)= 7.1 Hz, 9-H₃), 1.28–

[2ϫd, J_6,6-Me= 9.4 Hz, 6-(CH₃)₂], 1.28 (t, J_2Ј,1Ј= 7.1 Hz, 2Ј-H₂), 1.56 (m, 7-H₂, 8-H₂), 1.73 (br. s, 6-OH), 2.25 (s, 1-H₃), AB signal

1.60 (br. d, 5-OH), 1.70 (qqd, J_6,7= J_6,6-Me= 6.8, J_6,5= 5.8 Hz, 6-

H), AB signal (δ_A= 2.30, δ_B= 2.41, J_AB= 14.6 Hz, A part ad-

(δ_A= 2.33, δ_B= 2.42, J_AB= 14.6 Hz, A part additionally split by

4

J_A,4= J_A,6= 7.4 Hz, J_A,3= 1.4 Hz, B part additionally split by

4

ditionally split by J_A,5= 8.2 Hz, J_A,3= 7.9 Hz, J_A,2= 1.4 Hz, B

J_B,4= 7.2 Hz, J_B,6= 4.4 Hz, J_B,3= 1.5 Hz, 5-H₂), 3.79 (m_c, 6-H),

4

part additionally split by J_B,3= 7.0 Hz, J_B,5= 3.9 Hz, J_B,2

=

6.13 (ddd, J_3,4= 16.0, J_3,5-H(A)

=

⁴J_3,5-H(B)= 1.4 Hz, 3-H),

1.6 Hz, 4-H₂), 3.52 (m_c, 5-H), 4.18 (q, J_1Ј,2Ј= 7.1 Hz, 1Ј-H), 5.91 6.84 ppm (ddd, J_4,3= 16.0 Hz, J_4,5–H(A)= J_4,5–H(B)= 7.3 Hz, 4-H).

4

(ddd, J_2,3= 15.7, J_2,4-H(A)

=

⁴J_2,4-H(B)= 1.5 Hz, 2-H), 7.00 ppm

¹³C NMR (100 MHz, CDCl₃): δ = 14.03 (C-9), 18.84 (C-8), 27.02

(ddd, J_3,2= 15.7 Hz, J_3,4–H(A)= 7.8 Hz, J_3,4–H(B)= 6.9 Hz, 3-H).

(C-1), 39.52 (C-7), 40.46 (C-5), 70.46 (C-6), 133.49 (C-3), 144.52

¹³C NMR (100 MHz, CDCl₃): δ = 14.34 (C-2Ј), 17.31 and 18.78 (C-4), 198.55 ppm (C-2). IR (film): ν = 3425, 2960, 2935, 2875,

˜

[6-(CH₃)₂], 33.47 (C-6), 37.25 (C-4), 60.36 (C-1Ј), 75.42 (C-5), 1675, 1625, 1425, 1365, 1320, 1260, 1170, 1125, 1060, 1020, 985,

123.80 (C-2), 145.88 (C-3), 166.44 ppm (C-1). IR (film): ν = 3450,

850, 750 cm^–1. HRMS (CI, NH₃): calcd. for C₉H₂₀NO₂174.1494

[M + NH₄]⁺; found 174.1496 (+1.1 ppm).

˜

2960, 2900, 2875, 1715, 1650, 1465, 1385, 1365, 1310, 1270, 1215,

1165, 1095, 1045, 980 cm^–1. HRMS (CI, NH₃): calcd. for C₁₀H₁₉O₃

187.1334 [M + H]⁺; found 187.1335 (–0.4 ppm).

(S,E)-6-Hydroxy-7-methyloct-3-en-2-one [28b; as a mixture (82:18)

with (R,E)-6-hydroxy-7-methyloct-4-en-2-one (iso-28b)]: This com-

pound was prepared from 25b (69 mg, 0.35 mmol) as described for

26a. Flash chromatography (1ϫ12 cm, 5 mL, cyclohexane/EtOAc

7:1) provided the title compound (fractions 44–62, 30 mg, 55%) as

(R,E)-5-Hydroxy-N-methoxy-N-methyloct-2-enamide [27a; as a

mixture (90:10) with (R,E)-5-hydroxy-N-methoxy-N-methyloct-3-en-

amide (iso-27a)]: This compound was prepared from 24a (80 mg,

0.33 mmol) as described for 26a. Flash chromatography (1ϫ14 cm,

20

a yellow oil. Compound 28a (major isomer): [α] = –6.7, [α]

=

589

578

4812

www.eurjoc.org

Eur. J. Org. Chem. 2010, 4802–4822

1,3,5-Triols by Asymmetric Dihydroxylation and Deoxygenation

20

–7.6, [α] = –8.1, [α] = –14.6, [α] = –19.7 (c = 0.64, CHCl₃).

3420, 3090, 3065, 3030, 2960, 2890, 2360, 1955, 1870, 1720, 1655,

1605, 1540, 1495, 1465, 1455, 1385, 1365, 1315, 1265, 1210, 1175,

546

436

365

¹H NMR (300 MHz, CDCl₃/CHCl₃): δ = 0.93 and 0.94 [2 ϫ d,

J_7,7-Me= 6.7 Hz, 7-(CH₃)₂], 1.70 (m_c, 7-H), 1.76 (br. s, 6-OH), 2.24 1135, 1100, 1040, 975, 905, 860 cm^–1. C₁₈H₂₆O₄(306.40): calcd. C

(s, 1-H₃), AB signal (δ_A= 2.32, δ_B= 2.42, J_AB= 14.7 Hz, A part

70.56, H 8.55; found C 70.51, H 8.84.

additionally split by J_A,6= 8.2 Hz, J_A,4= 7.6 Hz, ⁴J_A,3= 0.8 Hz, B

Ethyl (R,E)-5-(4-Methoxybenzyloxy)oct-2-enoate (30a): Compound

26 (853 mg, 4.48 mmol) was dissolved in CH₂Cl₂(40 mL) and 4-

methoxybenzyl trichloroacetimidate (2.91 g, 10.3 mmol, 2.3 equiv.)

was added. A solution of pyridinium p-toluenesulfonate (676 mg,

2.69 mmol, 0.6 equiv.) in CH₂Cl₂(5 mL) was added over 10 min

and the resulting mixture was stirred for 11 d. After addition of

satd. aq. NaHCO₃(25 mL), the phases were separated and the aq.

phase was extracted with CH₂Cl₂(3ϫ30 mL). The combined or-

ganic phases were washed with brine (25 mL) and dried with

MgSO₄. The solvent was removed under reduced pressure, and

flash chromatography (4.5ϫ21.5 cm, 50 mL, cyclohexane/EtOAc

4

part additionally split by J_B,4= 6.9 Hz, J_B,6= 3.9 Hz, J_B,3

=

1.3 Hz, 5-H₂), 3.52 (m_c, 6-H), 6.14 (br. d, J_3,4= 16.0 Hz, 3-H),

6.86 ppm (ddd, J_4,3= 16.0 Hz, J_4,5–H(A)= J_4,5–H(B)= 7.2 Hz, 4-H).

¹³C NMR (100 MHz, CDCl₃): δ = 17.36 and 18.84 [7-(CH₃)₂],

27.02 (C-1), 33.68 (C-7), 37.46 (C-5), 75.60 (C-6), 133.38 (C-3),

145.13 (C-4), 198.50 ppm (C-2). IR (film): ν = 3425, 2960, 2930,

˜

2875, 1675, 1625, 1510, 1455, 1425, 1360, 1320, 1260, 1170, 1125,

1080, 1060, 1020, 980, 850 cm^–1. HRMS (CI, NH₃): calcd. for

C₉H₁₇O₂157.1229 [M + H]⁺; found 157.1225 (+2.3 ppm).

Ethyl (R,E)-5-(Benzyloxymethoxy)oct-2-enoate (29a): Compound

26 (604 mg, 3.24 mmol) was dissolved in 1,2-dichlorethane (32 mL) 40:1) provided the title compound (fractions 26–41, 1.06 g, 77%)

and benzyl chloromethyl ether (1.80 mL, 1.67 g, 13.0 mmol,

4.0 equiv.) and iPr₂NEt (2.15 mL, 2.03 g, 13.0 mmol, 4.0 equiv.) [α]

as a colorless oil, together with reisolated starting material (15%).

20

= +14.4, [α]

= +14.6, [α]

= +16.8, [α]

= +28.9,

589

578

546

436

20

were added. The reaction mixture was stirred under reflux for 4 h.

After the addition of H₂O (15 mL), the phases were separated and

the aq. phase was extracted with MTBE (3ϫ15 mL). The com-

bined organic phases were washed with brine (15 mL) and dried

with MgSO₄. The solvent was removed under reduced pressure and

flash chromatography (3.5ϫ19.5 cm, 50 mL, cyclohexane/EtOAc

50:1) provided the title compound (fractions 37–52, 824 mg, 83%)

[α]

= +44.5 (c = 0.69, CHCl₃). ¹H NMR (400 MHz, CDCl₃/

365

CHCl₃): δ = 0.90 (dd, J_8,7-H(A)= J_8,7-H(B)= 7.2 Hz, 8-H₃), 1.25–

1.60 (m, 6-H_2,7-H₂), 1.29 (t, J_2Ј,1Ј= 7.1 Hz, 2Ј-H₃), AB signal (δ_A

= 2.41, δ_B= 2.45, J_AB= 14.7 Hz, A part additionally split by J_A,3

= 7.4 Hz, J_A,5= 5.8 Hz, ⁴J_A,2= 1.5 Hz, B part additionally split by

J_B,3= 7.4 Hz, J_B,5= 5.8 Hz, ⁴J_B,2= 1.5 Hz, 4-H₂), 3.50 (m_c, approx-

imately interpretable as dddd, J_5,6-H(A)= 6.9, J_5,4-H(A)= J_5,4-H(B)

=

20

as a colorless oil. [α]

= +27.3, [α]

= +28.4, [α] = +32.5,

5.7, J_5,6-H(B)= 4.8 Hz, 5-H), 3.81 (s, OCH₃), 4.19 (q, J_1Ј,2Ј= 7.1 Hz,

1Ј-H₂), AB signal (δ_A= 4.43, δ_B= 4.48, J_AB= 11.1 Hz, OCH₂Ar),

589

578

546

20

[α]

436

= +58.8 (c = 0.65, CHCl₃). ¹H NMR (400 MHz, CDCl₃/

CHCl₃): δ = 0.93 (dd, J_8,7-H(A)= J_8,7-H(B)= 7.5 Hz, 8-H₃), 1.27 (t, 5.87 (ddd, J_2,3= 15.7, ⁴J_2,4-H(A)= ⁴J_2,4-H(B)= 1.5 Hz, 2-H), AAЈBBЈ

J_2Ј,1Ј= 7.1 Hz, 2Ј-H₃), 1.33–1.63 (m, 6-H_2,7-H₂), AB signal (δ_A

=

signal (peaks centered at δ_A= 6.87, δ_B= 7.25, 2ϫ ortho-H, 2ϫ

meta-H), 6.98 ppm (ddd, J_3,2= 15.6, J_3,4–H(A)= J_3,4–H(B)= 7.4 Hz,

3-H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.17 (C-2Ј), 14.35 (C-8),

18.68 (C-7), 36.46 (C-6), 36.95 (C-4), 55.35 (OCH₃), 60.25 (C-1Ј),

2.43, δ_B= 2.47, J_AB= 14.6 Hz, A part additionally split by J_A,3

4

7.5 Hz, J_A,5= 5.9 Hz, J_A,2= 1.5 Hz, B part additionally split by

J_B,3= 7.3 Hz, J_B,5= 5.7 Hz, ⁴J_B,2= 1.5 Hz, 4-H₂), 3.79 (m_c, approx-

imately interpretable as dddd, J_5,6-H(A)= 6.4, J_5,6-H(B)= 5.8, 70.88 (OCH₂Ar), 77.31 (C-5), 113.846 (2ϫ ortho-C), 123.43 (C-2),

J_5,4-H(A)= J_5,4-H(B)= 5.7 Hz, 5-H), 4.18 (q, J_1Ј,2Ј= 7.1 Hz, 1Ј-H₂), 129.40 (2ϫ meta-C), 130.72 (ipso-C), 145.61 (C-3), 159.26 (C-4ЈЈ),

4.62 (s, OCH₂OCH₂Ar), 4.79 (s, OCH₂OCH₂Ar), 5.88 (ddd, J_2,3

=

166.47 ppm (C-1). IR (film): ν = 3370, 2980, 2935, 2870, 2840,

˜

4

15.6, J_2,4-H(A)

=

⁴J_2,4-H(B)= 1.5 Hz, 2-H), 6.99 (ddd, J_3,2= 15.6, 2365, 2065, 1890, 1715, 1655, 1615, 1585, 1560, 1540, 1515, 1465,

J_3,4-H(A)= J_3,4-H(B)= 7.5 Hz, 3-H), 7.26–7.37 ppm (m, 2ϫ ortho-H, 1365, 1320, 1300, 1250, 1210, 1175, 1940, 980, 820 cm^–1. C₁₈H₂₆O₄

2ϫ meta-H, para-H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.17 (C-

2Ј), 14.33 (C-8), 18.67 (C-7), 36.56 (C-6), 37.32 (C-4), 60.28 (C-1Ј),

69.77 (OCH₂OCH₂Ar), 75.98 (C-5), 93.47 (OCH₂OCH₂Ar), 123.73

(C-2), 127.77 (para-C), 127.92 (2ϫ ortho-C) 128.50 (2ϫ meta-C),

(306.40): calcd. C 70.56, H 8.55; found C 70.35, H 8.68.

Ethyl (S,E)-5-(4-Methoxybenzyloxy)-6-methylhept-2-enoate (30b):

This compound was prepared from 26b (708 mg, 3.80 mmol) as

described for 30a. Flash chromatography (3.5ϫ19 cm, 50 mL, cy-

clohexane/EtOAc 40:1) provided the title compound (fractions 27–

137.89 (ipso-C), 145.23 (C-3), 166.38 ppm (C-1). IR (film): ν =

˜

3420, 3065, 3030, 2960, 2935, 2875, 1720, 1655, 1490, 1455, 1360,

1320, 1260, 1210, 1180, 1100, 1040, 985 cm^–1. C₁₈H₂₆O₄(306.40):

calcd. C 70.56, H 8.55; found C 70.19, H 8.41.

38, 815 mg, 70%) as a colorless oil, together with reisolated starting

20

material (21%). [α]

= +8.8 (c = 0.79, CHCl₃). ¹H NMR

365

(400 MHz, CDCl₃/CHCl₃): δ = 0.93 and 0.95 [2 ϫ d, J_6-Me,6

6.8 Hz, 6-(CH₃)₂], 1.30 (t, J_2Ј,1Ј= 7.1 Hz, 2Ј-H₂), 1.88 (qqd, J_6,7

J_6,6–Me= 6.8, J_6,5= 3.8 Hz, 6-H), AB signal (δ_A= 2.40, δ_B= 2.44,

=

Ethyl (S,E)-5-(Benzyloxymethoxy)-6-methylhept-2-enoate (29b):

This compound was prepared from 26b (1.01 g, 5.42 mmol) as de-

scribed for 26a. Flash chromatography (4ϫ18 cm, 50 mL, cyclo- J_AB= 14.6 Hz, A part additionally split by J_A,3= 7.6 Hz, J_A,5

=

4

hexane/EtOAc 30:1) provided the title compound (fractions 12–33,

6.2 Hz, J_A,2= 1.3 Hz, B part additionally split by J_B,3= 7.2 Hz,

J_B,5= 5.5 Hz, J_B,2= 1.6 Hz, 4-H₂), 3.26 (ddd, J_5,4–H(A)= J_5,4–H(B)

20

4

1.30 g, 78%) as a colorless oil. [α]

= +21.9, [α]

= +23.0,

589

578

[α]

= +26.4, [α]

= +48.2 (c = 1.03, CHCl₃). ¹H NMR

= J_5,6= 5.7 Hz, 5-H), 3.81 (s, OCH₃), 4.20 (q, J_1Ј,2Ј= 7.1 Hz, 1Ј-

H), AB signal (δ_A= 4.44, δ_B= 4.49, J_AB= 11.0 Hz, OCH₂Ar), 5.89

20

546

436

(400 MHz, CDCl₃/CHCl₃): δ = 0.94 and 0.95 [2 ϫ d, J_6-Me,6

6.8 Hz, 6-(CH₃)₂], 1.27 (t, J_2Ј,1Ј= 7.1 Hz, 2Ј-H₂), 1.88 (qqd, J_6,7

=

4

(ddd, J_2,3= 15.7, J_2,4–H(AHz)= J_2,4–H(B)= 1.5 Hz, 2-H), AAЈBBЈ

signal (peaks centered at δ_A= 6.88, δ_B= 7.27, 2ϫ ortho-H, 2ϫ

J_6,6-Me= 6.8, J_6,5= 3.8 Hz, 6-H), 2.44 (ddd, J_4,3= 7.4, J_4,5= 5.9,

⁴J_4,2= 1.5 Hz, 4-H₂), 3.56 (dt, J_5,4= J_5,6= 5.6 Hz, 5-H), 4.17 (q,

meta-H), 7.02 ppm (ddd, J_3,2= 15.6 Hz, J_3,4–H(A)= J_3,4–H(B)

=

J_1Ј,2Ј= 7.2 Hz, 1Ј-H), 4.63 (s, OCH₂OCH₂Ar), 4.78 (s, OCH₂O-

7.4 Hz, 3-H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.37 (C-2ЈЈ),

4

CH₂Ar), 5.90 (dt, J_2,3= 15.7, J_2,4= 1.5 Hz, 2-H), 7.02 (dt, J_3,2

=

18.27 and 18.31 [6-(CH₃)₂], 31.24 (C-6), 33.86 (C-4), 55.35 (OCH₃),

15.7, J_3,4= 7.5 Hz, 3-H), 7.26–7.36 ppm (m, 2ϫ ortho-H, 2ϫ meta- 60.22 (C-1ЈЈ), 71.74 (OCH₂Ar), 82.78 (C-5), 113.84 (2ϫ ortho-C),

H, para-H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.33 (C-2ЈЈ),18.08 123.19 (C-2), 129.44 (2ϫ meta-C), 130.80 (ipso-C), 146.29 (C-3),

and 18.16 (Me₂-6), 31.22 (C-6), 34.09 (C-4), 60.26 (C-1ЈЈ), 69.86

(OCH₂OCH₂Ar), 81.37 (C-5), 94.05 (OCH₂OCH₂Ar), 123.49 (C-

159.24 (C-4ЈЈ), 166.51 ppm (C-1). IR (film): ν = 3420, 2960, 2905,

˜

2875, 2840, 2065, 1720, 1655, 1615, 1585, 1515, 1465, 1385, 1365,

2), 127.75 (2ϫ para-C), 127.90 (2ϫ ortho-C), 128.49 (2ϫ meta-C), 1345, 1300, 1250, 1170, 1110, 1070, 1035, 975, 820 cm^–1. C₁₈H₂₆O₄

137.91 (ipso-C), 145.86 (C-3), 166.39 ppm (C-1). IR (film): ν =

(306.40): calcd. C 70.56, H 8.55; found C 70.56, H 8.72.

˜

Eur. J. Org. Chem. 2010, 4802–4822

www.eurjoc.org

4813

P. Walleser, R. Brückner

[α] = +40.8, [α] = +75.3, [α] = +134.1 (c = 0.46, CHCl₃).

FULL PAPER

20

546

20

436

20

365

Ethyl (R,E)-5-(tert-Butyldiphenylsilyloxy)oct-2-enoate (31a): Com-

pound 26 (265 mg, 1.42 mmol) was dissolved in DMF (7 mL) and

imidazole (387 mg, 5.68 mmol, 4.0 equiv.) was added. tert-Butyldi-

phenylsilyl chloride (0.740 mL, 781 mg, 2.84 mmol, 2.0 equiv.) was

added over 5 min and the mixture was stirred at 65 °C for 2 d. After

the addition of H₂O (35 mL), the phases were separated and the aq.

phase was extracted with MTBE (3ϫ4 mL). The combined organic

phases were washed with H₂O (3 mL) and brine (3 mL) and dried

with MgSO₄. The solvent was removed under reduced pressure,

and flash chromatography (3ϫ21 cm, 20 mL, cyclohexane/EtOAc

50:1) provided the title compound (fractions 17–27, 592 mg, 98%)

¹H NMR (400 MHz, CDCl₃/CHCl₃): δ = 0.92 (dd, J_8,7–H(A)

=

J_8,7–H(B)= 7.2 Hz, 8-H₃), 1.32–1.60 (m, 6-H₂, 7-H₂), AB signal (δ_A

= 2.47, δ_B= 2.51, J_AB= 14.6 Hz, A part additionally split by J_A,3

4

= 7.4 Hz, J_A,5= 5.9 Hz, J_A,2= 1.4 Hz, B part additionally split

4

by J_B,3= 7.5 Hz, J_B,5= 5.8 Hz, J_B,2= 1.5 Hz, 4-H₂), 3.23 (s,

NCH₃), 3.68 (s, OCH₃), 3.79 (m_c, approximately interpretable as

dddd, J_5,6–H(A)= 6.4 Hz, J_5,4–H(A)= J_5,4–H(B)= J_5,6–H(B)= 5.9 Hz,

5-H), 4.63 (s, OCH₂OCH₂Ar), AB signal (δ_A= 4.78, δ_B= 4.81, J_AB

4

= 7.1 Hz, OCH₂OCH₂Ar), 6.46 (ddd, J_2,3= 15.3 Hz, J_2,4–H(A)

=

⁴J_2,4–H(B)= 1.3 Hz, 2-H), 7.00 (ddd, J_3,2= 15.0 Hz, J_3,4–H(A)

20

as a colorless oil. [α]

= +33.8, [α]

= +35.2, [α] = +40.8,

J_3,4–H(B)= 7.4 Hz, 3-H), 7.26–7.37 ppm (m, 2ϫ ortho-H, para-H,

2ϫ ortho-H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.20 (C-8), 18.67

(C-7), 32.42 [N(CH₃)(OCH₃)], 37.72 (C-6), 37.72 (C-4), 61.76

[N(CH₃)(OCH₃)], 69.72 (OCH₂OCH₂Ar), 76.34 (C-5), 93.59

(OCH₂OCH₂Ar), 121.13 (C-2), 127.82 (para-C), 127.97 (2ϫ ortho-

C) 128.50 (2ϫ meta-C), 137.97 (ipso-C), 143.68 (C-3), 166.70 ppm

589

578

546

20

[α]

436

= +75.3, [α]

= +134.1 (c = 0.46, CHCl₃). ¹H NMR

365

(400 MHz, CDCl₃/CHCl₃): δ = 0.75 (dd, J_8,7–H(A)= J_8,7–H(B)

7.3 Hz, 8-H₃), 1.05 (s, 2ЈЈ-H₉), 1.20–1.30 (m, 7-H₂), 1.28 (t, J_2Ј,1Ј

7.1 Hz, 2Ј-H₃), 1.38–1.45 (m, 6-H₂), AB signal (δ_A= 2.27, δ_B

=

2.32, J_AB= 14.2 Hz, A part additionally split by J_A,3= 7.7 Hz, J_A,5

= 5.4 Hz, ⁴J_A,2= 1.3 Hz, B part additionally split by J_B,3= 7.4 Hz,

(C-1). IR (film): ν = 3470, 3065, 3030, 2960, 2935, 2875, 1735, 1665,

˜

4

J_B,5= 5.9 Hz, J_B,2= 1.3 Hz, 4-H₂), 3.84 (dddd, J_5,6–H(A)= J_5,6–

1635, 1490, 1455, 1415, 1380, 1295, 1170, 1100, 1040, 1000 cm^–1.

= J_5,4–H(A)= J_5,4–H(B)= 5.7 Hz, 5-H), 4.17 (q, J_1Ј,2Ј= 7.1 Hz,

C₁₈H₂₇NO₄(306.40): calcd. C 67.26, H 8.47, N 4.36; found C

67.96, H 8.74, N 4.08.

H(B)

4

1Ј-H₂), 5.72 (ddd, J_2,3= 15.7 Hz, J_2,4–H(A)

=

⁴J_2,4–H(B)= 1.5 Hz,

2-H), 6.90 (ddd, J_3,2= 15.7 Hz, J_3,4–H(A)= J_3,4–H(B)= 7.5 Hz, 3-H),

7.34–7.45 (m, 4ϫ ortho-H, 2ϫ para-H), 7.65–7.69 ppm (m, 4ϫ

meta-H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.09 (C-2Ј), 14.36 (C-

8), 18.20 (C-7), 19.45 (C-1ЈЈ), 27.13 (C₃-2ЈЈ), 38.81 (C-6), 39.43 (C-

4), 60.19 (C-1Ј), 72.10 (C-5), 123.43 (C-2), 127.60 and 127.62 (4ϫ

meta-C), 129.69 and 129.70 (2ϫ para-C), 134.26 and 134.31 (2ϫ

ipso-C), 135.99 and 136.02 (4ϫ ortho-C), 145.71 (C-3), 166.67 ppm

(S,E)-5-(Benzyloxymethoxy)-N-methoxy-N,6-dimethylhept-2-

enamide (32b): This compound was prepared from 29b (1.41 g,

4.60 mmol) as described for 13a. Flash chromatography

(3ϫ18.5 cm, 20 mL, cyclohexane/EtOAc 4:1) provided the title

20

compound (fractions 28–48, 1.08 g, 73%) as a colorless oil. [α]

589

20

= +32.6, [α]

= +33.8, [α]

= +39.0, [α]

= +70.5, [α]

=

578

546

436

365

1

+122.3 (c = 0.89, CHCl₃). H NMR (400 MHz, CDCl₃/CHCl₃): δ

= 0.95 and 0.95 [2ϫd, J_6-Me,6= 6.8 Hz, 6-(CH₃)₂], 1.89 (qqd, J_6,7

(C-1). IR (film): ν = 3420, 3070, 2960, 2930, 2860, 1720, 1655,

˜

1465, 1465, 1425, 1390, 1365, 1320, 1265, 1205, 1170, 1110, 1040,

985, 820 cm^–1. C₂₆H₂₈O₃Si (424.65): calcd. C 73.54, H 8.54; found

C 73.28, H 8.47.

= J_6,6–Me= 6.8 Hz, J_6,5= 3.8 Hz, 6-H), AB signal (δ_A= 2.46, δ_B

=

2.50, J_AB= 14.5 Hz, A part additionally split by J_A,3= 7.4 Hz, J_A,5

= 5.8 Hz, ⁴J_A,2= 1.5 Hz, B part additionally split by J_B,3= 7.8 Hz,

4

Ethyl (R,E)-5-(tert-Butyldiphenylsilyloxy)-6-methylhept-2-enoate J_B,5= 6.5 Hz, J_B,2= 1.4 Hz, 4-H₂), 3.23 (s, NCH₃), 3.57 (ddd,

(31b): This compound was prepared from 26b (241 mg, 1.29 mmol)

as described for 31a. Flash chromatography (2ϫ20.5 cm, 20 mL,

cyclohexane/EtOAc 40:1) provided the title compound (fractions

J_5,4–H(A)= J_5,4–H(B)= J_5,6= 5.6 Hz, 5-H), 3.67 (s, OCH₃), 4.63

(s, OCH₂OCH₂Ar), AB signal (δ_A= 4.78, δ_B= 4.80, J_AB= 7.1,

4

OCH₂OCH₂Ar), 6.48 (ddd, J_2,3= 15.3 Hz, J_2,4–H(A)= ⁴J_2,4–H(B)

=

20

24–33, 434 mg, 79%) as a colorless oil. [α]

= +46.3, [α]

=

1.4 Hz, 2-H), 7.02 (ddd, J_3,2= 15.3 Hz, J_3,4–H(A)= J_3,4–H(B)

589

578

20

+49.0, [α] = +55.9, [α] = +102.1, [α] = +178.2 (c = 0.63,

7.6 Hz, 3-H), 7.26–7.36 ppm (m, 2ϫ ortho-H, 2ϫ meta-H, para-

H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.88 and 18.32 [6-(CH₃)₂],

31.27 (C-6), 32.41 [N(CH₃)(OCH₃)], 34.52 (C-4), 61.74

[N(CH₃)(OCH₃)], 69.80 (OCH₂OCH₂Ar), 81.65 (C-5), 94.19

(OCH₂OCH₂Ar), 120.09 (C-2), 127.70 (para-C), 127.94 (2ϫ ortho-

C) 128.48 (2ϫ meta-C), 137.98 (ipso-C), 144.26 (C-3), 166.72 ppm

546

436

365

CHCl₃). ¹H NMR (400 MHz, CDCl₃/CHCl₃): δ = 0.84 and 0.91

[2ϫd, J_6-Me,6= 6.8 Hz, 6-(CH₃)₂], 1.07 (s, 2ЈЈЈ-H₉), 1.26 (t, J_2ЈЈ,1ЈЈ

= 7.1 Hz, 2ЈЈ-H₃), 1.71 (qqd, J_6,7= J_6,6–Me= 6.8 Hz, J_6,5= 3.8 Hz,

6-H), AB signal (δ_A= 2.25, δ_B= 2.29, J_AB= 15.6 Hz, A part ad-

4

ditionally split by J_A,3= 7.8 Hz, J_A,5= 6.3 Hz, J_A,2= 1.5 Hz, B

4

part additionally split by J_B,3= 7.6 Hz, J_B,5= 6.3 Hz, J_B,2

1.4 Hz, 4-H₂), 3.66 (ddd, J_5,4–H(B)= J_5,4–H(B)= 6.1 Hz, J_5,6

=

(C-1). IR (film): ν = 3275, 3065, 3030, 2960, 2895, 1720, 1665,

˜

1635, 1500, 1455, 1415, 1380, 1295, 1165, 1100, 1040, 1005, 840,

820 cm^–1. C₁₈H₂₇NO₄(321.41): calcd. C 67.26, H 8.47, N 4.36;

found C 66.97, H 8.31, N 4.35.

3.8 Hz, 5-H), 4.14 (q, J_1ЈЈ,2ЈЈ= 7.2 Hz, 1ЈЈ-H), 5.65 (ddd, J_2,3

4

15.6 Hz, J_2,4–H(A)

=

⁴J_2,4–H(B)= 1.5 Hz, 2-H), 6.78 (ddd, J_3,2

15.5 Hz, J_3,4–H(A)= J_3,4–H(B)= 7.6 Hz, 3-H), 7.34–7.46 (m, 4ϫ or-

tho-H, 2ϫ para-H), 7.65–7.71 ppm (m, 4ϫ meta-H). ¹³C NMR

(100 MHz, CDCl₃): δ = 14.34 (C-2ЈЈ), 17.15 and 18.38 [6-(CH₃)₂],

19.62 (C-1ЈЈЈ), 27.18 (C₃-2ЈЈЈ), 32.80 (C-6), 36.58 (C-4), 60.15 (C-

1ЈЈ), 76.96 (C-5), 123.10 (C-2), 127.55 and 127.60 (4ϫ meta-C),

129.65 and 129.71 (2ϫ para-C), 134.07 and 134.39 (2ϫ ipso-C),

136.10 and 136.11 (4ϫ ortho-C), 146.16 (C-3), 166.39 ppm (C-1).

(R,E)-N-Methoxy-5-(4-methoxybenzyloxy)-N-methyloct-2-enamide

(33a): This compound was prepared from 30a (522 mg, 1.70 mmol)

as described for 13a. Flash chromatography (2ϫ13.5 cm, 20 mL,

cyclohexane/EtOAc 4:1) provided the title compound (fractions 30–

20

54, 356 mg, 65%) as a colorless oil. [α] = +33.9, [α] = +53.9,

436

365

(c = 0.27 CHCl₃). ¹H NMR (400 MHz, CDCl₃/CHCl₃): δ = 0.90

(dd, J_8,7–H(A)= J_8,7–H(B)= 7.2 Hz, 8-H₃), 1.28–1.60 (m, 6-H₂, 7-

H₂), AB signal (δ_A= 2.44, δ_B= 2.51, J_AB= 14.5 Hz, A part ad-

IR (film): ν = 3395, 3070, 3050, 2960, 2935, 2895, 2860, 1665, 1635,

˜

1470, 1425, 1385, 1305, 1260, 1180, 1110, 1055, 1005, 940,

820 cm^–1. C₂₆H₂₈O₃Si (424.65): calcd. C 73.54, H 8.54; found C

73.37, H 8.47.

4

ditionally split by J_A,3= 7.5 Hz, J_A,5= 6.0 Hz, J_A,2= 1.5 Hz, B

4

part additionally split by J_B,3= 7.4 Hz, J_B,5= 5.9 Hz, J_B,2

=

1.4 Hz, 4-H₂), 3.24 (s, NCH₃), 3.52 (m_c, approximately interpret-

(R,E)-5-(Benzyloxymethoxy)-N-methoxy-N-methyloct-2-enamide able as dddd, J_5,6–H(A)= 6.7 Hz, J_5,4–H(A)= J_5,6–H(B)= 6.1 Hz,

(32a): This compound was prepared from 29b (1.41 g, 4.60 mmol)

as described for 13a. Flash chromatography (3ϫ18.5 cm, 20 mL,

cyclohexane/EtOAc 5:1) provided the title compound (fractions 35–

J_5,6–H(B)= 4.5 Hz, 5-H), 3.68 (s, OCH₃), 3.81 (s, 4Ј-OCH₃), AB

signal (δ_A= 4.43, δ_B= 4.50, J_AB= 11.1 Hz, OCH₂Ar), 6.46 (ddd,

J_2,3= 15.4 Hz, ⁴J_2,4–H(A)= ⁴J_2,4–H(B)= 1.3 Hz, 2-H), AAЈBBЈ signal

(peaks centered at δ_A= 6.86, δ_B= 7.26, 2ϫ ortho-H, 2ϫ meta-H),

20

58, 555 mg, 70%) as a colorless oil. [α] = +33.8, [α] = +35.2,

589

578

4814

www.eurjoc.org

Eur. J. Org. Chem. 2010, 4802–4822

1,3,5-Triols by Asymmetric Dihydroxylation and Deoxygenation

20

7.00 ppm (ddd, J_3,2= 15.3 Hz, J_3,4–H(A)= J_3,4–H(B)= 7.6 Hz, 3-H).

[α]

= +48.8, [α]

= +51.0, [α]

= +58.8, [α]

= +109.0,

589

578

546

436

¹³C NMR (100 MHz, CDCl₃): δ = 14.16 (C-8), 18.63 (C-7), 32.38 [α]

= +194.8 (c = 1.22, CHCl₃). ¹H NMR (400 MHz, CDCl₃/

20

365

[N(CH₃)(OCH₃)], 36.50 (C-6), 37.38 (C-4), 55.30 (H₃CO-4Ј), 61.70 CHCl₃): δ = 0.86 and 0.91 [2ϫd, J_6-Me,6= 6.8 Hz, 6-(CH₃)₂], 1.07

[N(CH₃)(OCH₃)], 70.92 (OCH₂Ar), 77.61 (C-5), 113.79 (2ϫ ortho- (s, 2Ј-H₉), 1.71 (qqd, J_6,6–Me= J_6,7= 6.8 Hz, J_6,5= 3.7 Hz, 6-H),

C), 120.84 (C-2), 129.33 (2ϫ meta-C), 130.82 (ipso-C), 144.05 (C- AB signal (δ_A= 2.28, δ_B= 2.36, J_AB= 14.3 Hz, A part additionally

4

3), 159.17 (para-C), 166.76 ppm (C-1). IR (film): ν = 3395, 2960,

split by J_A,3= 7.2 Hz, J_A,5= 5.6 Hz, J_A,2= 1.3 Hz, B part ad-

˜

4

2935, 2870, 2365, 1665, 1635, 1615, 1515, 1460, 1420, 1380, 1300,

1250, 1175, 1070, 1035, 995, 820 cm^–1. C₁₈H₂₇NO₄(321.41): calcd.

C 67.26, H 8.47, N 4.36; found C 67.02, H 8.77, N 4.18.

ditionally split by J_B,3= 7.3 Hz, J_B,5= 7.2 Hz, J_B,2= 1.3 Hz, 4-

H₂), 3.20 (s, NCH₃), 3.62 (s, OCH₃), 3.68 (m_c, approximately inter-

pretable as ddd, J_5,4–H(B)= 7.2 Hz, J_5,4–H(A)= 5.2 Hz, J_5,6= 3.7 Hz,

5-H), 6.22 [br. d, J_2,3= 15.5 Hz, 2-H], 6.78 (ddd, J_3,2= 15.3 Hz,

J_3,4–H(A)= J_3,4–H(B)= 7.5 Hz, 3-H), 7.34–7.45 (m, 4ϫ ortho-H, 2ϫ

para-H), 7.66–7.71 ppm (m, 4ϫ meta-H). ¹³C NMR (100 MHz,

CDCl₃): δ = 16.75 and 18.93 [6-(CH₃)₂], 19.65 (C-1Ј), 27.19 (C₃-

2Ј), 32.43 [N(CH₃)(OCH₃)], 37.31 (C-6), 37.82 (C-4), 61.70

[N(CH₃)(OCH₃)], 77.30 (C-5), 120.48 (C-2), 127.53 and 127.59 (4ϫ

meta-C), 129.59 and 129.67 (2ϫ para-C), 134.10 and 134.54 (2ϫ

ipso-C), 136.09 and 136.12 (4ϫ ortho-C), 144.33 (C-3), 166.73 ppm

(R,E)-N-Methoxy-5-(4-methoxybenzyloxy)-N,6-dimethylhept-2-

enamide (33b): This compound was prepared from 30b (926 mg,

3.02 mmol) as described for 13a. Flash chromatography

(3.5ϫ14 cm, 50 mL, cyclohexane/EtOAc 4:1) provided the title

compound (fractions 9–18, 962 mg, 99 %) as a colorless oil. ¹H

NMR (400 MHz, CDCl₃/CHCl₃): δ = 0.92 and 0.94 [2ϫd, J_6-Me,6

= 6.7 Hz, 6-(CH₃)₂], 1.87 (qqd, J_6,7= J_6,6–Me= 6.8 Hz, J_6,5

=

5.3 Hz, 6-H), 2.45 (ddd, J_4,3= 7.4 Hz, J_4,5= 6.0 Hz, ⁴J_4,2= 1.4 Hz,

4-H₂), 3.24 (s, NCH₃), 3.28 (dt, J_5,4= J_5,6= 5.6 Hz, 5-H), 3.66 (s,

(C-1). IR (film): ν = 3395, 3070, 3050, 2960, 2935, 2895, 2860,

˜

1665, 1635, 1470, 1425, 1385, 1305, 1260, 1180, 1110, 1055, 1005,

940, 820 cm^–1. C₂₆H₃₇NO₃Si (439.66): calcd. C 71.03, H 8.48, N

3.19; found C 70.74, H 8.49, N 3.15.

OCH₃), 3.79 (s, 4Ј-OCH₃), AB signal (δ_A= 4.43, δ_B= 4.48, J_AB

=

4

11.1 Hz, OCH₂Ar), 6.46 (dt, J_2,3= 15.4 Hz, J_2,4= 1.4 Hz, 2-H),

AAЈBBЈ signal (peaks centered at δ_A= 6.86, δ_B= 7.26, 2ϫ ortho-

H, 2ϫ meta-H), 7.03 ppm (dt, J_3,2= 15.2 Hz, J_3,4= 7.6 Hz, 3-H).

¹³C NMR (100 MHz, CDCl₃): δ = 18.10 and 18.41 [6-(CH₃)₂],

31.36 (C-6), 32.42 [N(CH₃)(OCH₃)], 34.40 (C-4), 55.34 (H₃CO-4Ј),

61.72 [N(CH₃)(OCH₃)], 71.85 (OCH₂Ar), 83.00 (C-5), 113.78 (2ϫ

ortho-C), 120.64 (C-2), 129.40 (2ϫ meta-C), 130.96 (ipso-C), 144.77

(R,E)-6-(Benzyloxymethoxy)non-3-en-2-one (35a): This compound

was prepared from 32a (326 mg, 1.01 mmol) as described for 14a.

Flash chromatography (3ϫ16.5 cm, 20 mL, cyclohexane/EtOAc

10:1) provided the title compound (fractions 25–35, 205 mg, 73%)

20

as a colorless oil. [α]

= +30.9, [α]

= +32.4, [α]

= +37.4,

589

578

546

20

[α]

436

= +69.9, [α]

= +125.1 (c = 0.89, CHCl₃). ¹H NMR

(400 MHz, CDCl₃/CHCl₃): δ = 0.93 (dd, J_9,8–H(A)= J_9,8–H(B)

7.3 Hz, 9-H₃), 1.30–1.61 (m, 7-H₂, 8-H₂), 2.21 (s, 1-H₃), AB signal

(δ_A= 2.44, δ_B= 2.50, J_AB= 14.6 Hz, A part additionally split by

365

(C-3), 159.16 (para-C), 166.86 ppm (C-1). IR (film): ν = 3470, 3065,

˜

=

2960, 2935, 2905, 2870, 2835, 2065, 1665, 1635, 1615, 1585, 1515,

1465, 1440, 1415, 1380, 1300, 1250, 1175, 1150, 1110, 1070, 1035,

1000, 975, 820 cm^–1. C₁₈H₂₇NO₄(321.41): calcd. C 67.26, H 8.47,

N 4.36; found C 67.05, H 8.69, N 4.16.

4

J_A,4= 7.4 Hz, J_A,6= 5.8 Hz, J_A,3= 1.5 Hz, B part additionally

4

split by J_B,4= 7.0 Hz, J_B,6= 5.4 Hz, J_B,3= 1.5 Hz, 5-H₂), 3.80

(R,E)-5-(tert-Butyldiphenylsilyloxy)-N-methoxy-N-methyloct-2-

enamide (34a): This compound was prepared from 31a (1.02 g,

2.40 mmol) as described for 13a. Flash chromatography

(3ϫ16.5 cm, 20 mL, cyclohexane/EtOAc 7:1) provided the title

compound (fractions 16–38, 919 mg, 87 %) as a colorless oil.

(dddd, J_6,7–H(A)= 6.8 Hz, J_6,7–H(B)= J_6,5–H(B)= J_6,5–H(A)= 5.5 Hz,

5-H), 4.62 (s, OCH₂OCH₂Ar), AB signal (δ_A= 4.79, δ_B= 4.81, J_AB

4

= 7.2 Hz, OCH₂OCH₂Ar), 6.12 (ddd, J_3,4= 16.0 Hz, J_3,5–H(A)

=

⁴J_3,5–H(B)= 1.5 Hz, 3-H), 6.83 (ddd, J_4,3= 16.0 Hz, J_4,5–H(A)

J_4,5–H(B)= 7.3 Hz, 4-H), 7.26–7.37 ppm (m, 2ϫ ortho-H, 2ϫ meta-

H, para-H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.17 (C-9), 18.70

(C-8), 26.89 (C-1), 36.75 (C-7), 37.59 (C-5), 69.79 (OCH₂OCH₂Ar),

76.10 (C-6), 93.56 (OCH₂OCH₂Ar), 127.82 (2ϫ ortho-C, para-C),

128.55 (2ϫ meta-C), 133.52 (C-3), 137.82 (ipso-C), 144.38 (C-4),

20

[α]

= +30.5, [α]

= +32.5, [α]

= +37.4, [α]

= +69.4,

589

578

546

436

20

= +126.0 (c = 1.0, CHCl₃). ¹H NMR (400 MHz, CDCl₃/

365

CHCl₃): δ = 0.76 (dd, J_8,7–H(A)= J_8,7–H(B)= 7.3 Hz, 8-H₃), 1.06 (s,

2Ј-H₉), 1.20–1.35 (m, 7-H₂), 1.40–1.47 (m, 6-H₂), AB signal (δ_A

=

2.31, δ_B= 2.38, J_AB= 14.1 Hz, A part additionally split by J_A,3

198.43 ppm (C-2). IR (film): ν = 3500, 3065, 3030, 2960, 2935,

˜

4

7.6 Hz, J_A,5= 4.8 Hz, J_A,2= 1.6 Hz, B part additionally split by

2875, 1700, 1675, 1630, 1495, 1455, 1430, 1360, 1320, 1255, 1205,

1165, 1100, 1080, 1040, 985, 910, 815, 740 cm^–1. HRMS (CI, NH₃):

calcd. for C₁₇H₂₈NO₃294.2069 [M + NH₄]⁺; found 294.2068 (–

0.4 ppm). C₁₇H₂₄O₃(276.37): calcd. C 73.88, H 8.75; found C

73.72, H 8.75.

4

J_B,3= 7.5 Hz, J_B,5= 6.5 Hz, J_B,2= 1.3 Hz, 4-H₂), 3.22 (s, NCH₃),

3.64 (s, OCH₃), 3.85 (dddd, J_5,6–H(A)= J_5,6–H(B)= J_5,4–H(B)= 6.1 Hz,

4

J_5,4–H(A)= 4.9 Hz, 5-H), 6.30 (ddd, J_2,3= 15.4 Hz, J_2,4–H(A)

=

⁴J_2,4–H(B)= 1.5 Hz, 2-H), 6.89 (ddd, J_3,2= 15.3 Hz, J_3,4–H(A)

J_3,4–H(B)= 7.6 Hz, 3-H), 7.34–7.45 (m, 4ϫ ortho-H, 2ϫ para-H),

7.66–7.71 ppm (m, 4ϫ meta-H). ¹³C NMR (100 MHz, CDCl₃): δ

= 14.09 (C-8), 18.03 (C-7), 19.44 (C-1Ј), 27.12 (C₃-2Ј), 32.40

[N(CH₃)(OCH₃)], 38.59 (C-6), 39.79 (C-4), 61.70 [N(CH₃)(OCH₃)],

72.26 (C-5), 120.88 (C-2), 127.58 and 127.59 (4ϫ meta-C), 129.64

and 129.68 (2ϫ para-C), 134.34 and 134.38 (2ϫ ipso-C), 135.97

and 136.02 (4 ϫ ortho-C), 143.91 (C-3), 166.78 ppm (C-1). IR

(S,E)-6-(Benzyloxymethoxy)-7-methyloct-3-en-2-one (35b): This

compound was prepared from 32b (580 mg, 1.80 mmol) as de-

scribed for 14a. Flash chromatography (3ϫ17 cm, 20 mL, cyclo-

hexane/EtOAc 10:1) provided the title compound (fractions 27–44,

20

419 mg, 84%) as a colorless oil. [α]

= +21.7, [α]

= +22.9,

589

578

[α] = +26.6, [α] = +49.9, [α] = +90.2 (c = 0.79, CHCl₃). ¹H

20

546

436

365

NMR (400 MHz, CDCl₃/CHCl₃): δ = 0.94 and 0.96 [2ϫd, J_7-Me,7

= 6.8 Hz, 7-(CH₃)₂], 1.87 (qqd, J_7,8= J_7,7–Me= 6.9 Hz, J_7,6

(film): ν = 3395, 3070, 3050, 2960, 2930, 2860, 1665, 1690, 1590,

˜

=

1465, 1425, 1380, 1260, 1175, 1110, 1040, 1005, 940, 895, 865,

820 cm^–1. C₂₆H₃₇NO₃Si (439.66): calcd. C 71.03, H 8.48, N 3.19;

found C 70.86, H 8.47, N 3.01.

3.7 Hz, 7-H), 2.18 (s, 1-H₃), AB signal (δ_A= 2.45, δ_B= 2.48, J_AB

= 15.5 Hz, A part additionally split by J_A,4= 7.7 Hz, J_A,6= 5.9 Hz,

⁴J_A,3= 1.3 Hz, B part additionally split by J_B,4= 7.6 Hz, J_B,6

=

4

(S,E)-5-(tert-Butyldiphenylsilyloxy)-N-methoxy-N,6-dimethylhept-

2-enamide (34b): This compound was prepared from 31b (1.47 g,

3.46 mmol) as described for 13a. Flash chromatography

(3.5ϫ15.5 cm, 20 mL, cyclohexane/EtOAc 7:1) provided the title

compound (fractions 19–38, 1.14 mg, 75 %) as a colorless oil.

5.7 Hz, J_B,3= 1.5 Hz, 5-H₂), 3.56 (ddd, J_6,5–H(A)= J_6,5–H(B)= J_6,7

= 5.6 Hz, 6-H), 4.63 (s, OCH₂OCH₂Ar), AB signal (δ_A= 4.79, δ_B

= 4.81, J_AB= 7.1 Hz, OCH₂OCH₂Ar), 6.13 (ddd, J_3,4= 16.0,

⁴J_3,5–H(A)

=

⁴J_3,5–H(B)= 1.4, 3-H), 6.85 (ddd, J_4,3= 15.9 Hz,

J_4,5–H(A)= J_4,5–H(B)= 7.3 Hz, 4-H), 7.26–7.37 ppm (m, 2ϫ ortho-

Eur. J. Org. Chem. 2010, 4802–4822

www.eurjoc.org

4815

P. Walleser, R. Brückner

H, 2ϫ meta-H, para-H). ¹³C NMR (100 MHz, CDCl₃): δ = 18.13 (400 MHz, CDCl₃/CHCl₃): δ = 0.77 (dd, J_8,7–H(A)= J_8,7–H(B)

FULL PAPER

=

and 18.18 [7-(CH₃)₂], 26.81 (C-1), 31.43 (C-7), 34.43 (C-5), 69.86 7.3 Hz, 9-H₃), 1.06 (s, 2Ј-H₉), 1.19–1.33 (m, 8-H₂), 1.40–1.48 (m, 7-

(OCH₂OCH₂Ar), 81.66 (C-6), 94.19 (C-OCH₂OCH₂Ar), 127.76 H₂), 2.15 (s, 1-H₃), AB signal (δ_A= 2.30, δ_B= 2.35, J_AB= 14.4 Hz,

4

(2ϫ ortho-C), 127.81 (para-C), 128.54 (2ϫ meta-C), 133.28 (C-3), A part additionally split by J_A,4= 7.4 Hz, J_A,6= 5.5 Hz, J_A,3

=

137.82 (ipso-C), 145.10 (C-4), 198.43 ppm (C-2). IR (film): ν =

1.5 Hz, B part additionally split by J_B,4= 7.2 Hz, J_B,6= 5.6 Hz,

˜

3310, 3065, 3030, 2960, 2885, 2365, 1955, 1870, 1695, 1675, 1630,

1500, 1465, 1455, 1425, 1385, 1360, 1290, 1255, 1210, 1165, 1135,

1100, 1040, 970, 905, 855 cm^–1. C₁₇H₂₄O₃(276.37): calcd. C 73.88,

H 8.75; found C 73.95, H 8.48.

⁴J_B,3= 1.5 Hz, 5-H₂), 3.87 (dddd, J_6,7–H(A)= J_6,7–H(B)= J_6,5–H(B)

=

J _{6 , 5 – H ( A )}= 5 . 7 H z , 5 - H ) , 5 . 9 6 ( d d d , J_{3 , 4}= 1 5 . 8 H z ,

4

⁴J_3,5–H(A)= J_3,5–H(B)= 1.4 Hz, 2-H), 6.73 (ddd, J_4,3= 15.5 Hz,

J_4,5–H(A)= J_4,5–H(B)= 7.7 Hz, 3-H), 7.35–7.46 (m, 4ϫ ortho-H, 2ϫ

para-H), 7.65–7.69 ppm (m, 4ϫ meta-H). ¹³C NMR (100 MHz,

CDCl₃): δ = 14.08 (C-9), 18.24 (C-8), 19.46 (C-1Ј), 26.66 (C-1),

27.10 (C₃-2Ј), 39.06 (C-7), 39.63 (C-5), 72.18 (C-6), 127.66 and

127.68 (4ϫ meta-C), 129.77 and 129.80 (2ϫ para-C), 133.40 (C-3),

134.15 and 134.25 (2ϫ ipso-C), 135.97 and 136.01 (4ϫ ortho-C),

(R,E)-6-(4-Methoxybenzyloxy)non-3-en-2-one (36a): This com-

pound was prepared from 33a (275 mg, 0.86 mmol) as described

for 14a. Flash chromatography (2.5ϫ15.5 cm, 20 mL, cyclohexane/

EtOAc 10:1) provided the title compound (fractions 21–32, 208 mg,

88%) as a colorless oil. [α] = +16.0 (c = 0.49, CHCl₃). ¹H NMR

20

365

145.09 (C-4), 198.56 ppm (C-2). IR (film): ν = 3395, 3070, 3050,

˜

(400 MHz, CDCl₃/CHCl₃): 0.92 (dd, J_9,8–H(A)= J_9,8–H(B)= 7.2 Hz,

3000, 2960, 2930, 2860, 1700, 1675, 1630, 1590, 1470, 1465, 1425,

1390, 1360, 1250, 1175, 1110, 1070, 1040, 985, 940, 895, 820 cm^–1.

C₂₅H₃₄O₂Si (394.62): calcd. C 76.09, H 8.68; found C 75.85, H 8.71.

9-H₃), 1.29–1.63 (m, 7-H₂, 8-H₂), 2.24 (s, 1-H₃), AB signal (δ_A

=

2.43, δ_B= 2.48, J_AB= 14.6 Hz, A part additionally split by J_A,4

4

7.3 Hz, J_A,6= 6.0 Hz, J_A,3= 1.3 Hz, B part additionally split by

J_B,4= 7.1 Hz, J_B,6= 5.4 Hz, ⁴J_B,3= 1.5 Hz, 5-H₂), 3.52 (m_c, approx-

imately interpretable as dddd, J_6,7–H(A)= 6.5, J_6,5–H(A)= J_6,5–H(B)

= 5.7 Hz, J_6,7–H(B)= 5.0 Hz, 6-H), 3.81 (s, OCH₃), 4.47 (s,

OCH₂Ar), 6.11 (ddd, J_3,4= 16.0 Hz, ⁴J_3,5–H(A)= ⁴J_3,5–H(B)= 1.4 Hz,

3-H), 6.81 ppm (ddd, J_4,3= 16.0 Hz, J_4,5–H(A)= J_4,5–H(B)= 7.3 Hz,

4-H), AAЈBBЈ signal (peaks centered at δ_A= 6.89 and δ_B= 7.26,

2ϫ ortho-H, 2ϫ meta-H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.18

(C-9), 18.67 (C-8), 26.82 (C-1), 36.44 (C-5) 37.13 (C-7), 55.35

(OCH₃), 70.84 (OCH₂Ar), 77.23 (C-6), 113.90 (2ϫ meta-C), 129.43

(2ϫ ortho-C), 130.64 (ipso-C), 133.32 (C-3), 144.86 (C-4), 159.31

(R,E)-6-(tert-Butyldiphenylsilyloxy)-7-methyloct-3-en-2-one (37b):

This compound was prepared from 34b (584 mg, 1.32 mmol) as

described for 14a. Flash chromatography (3ϫ19.5 cm, 20 mL, cy-

clohexane/EtOAc 10:1) provided the title compound (fractions 7–

20

11, 409 mg, 78%) as a colorless oil. [α] = +48.1, [α] = +50.4,

589

578

20

[α] = +58.2, [α] = +110.3, [α] = +217.4 (c = 1.12, CHCl₃).

546

436

365

¹H NMR (400 MHz, CDCl₃/CHCl₃): δ = 0.85 and 0.93 [2 ϫ d,

J_7-Me,7= 6.8 Hz, 7-(CH₃)₂], 1.07 (s, 2ЈЈ-H₉), 1.74 (qqd, J_7,8

=

J_7,7–Me= 6.8 Hz, J_7,6= 3.9 Hz, 7-H), 2.05 (s, 1-H₃), AB signal (δ_A

= 2.27, δ_B= 2.31, J_AB= 14.6 Hz, A part additionally split by J_A,4

4

= 7.3 Hz, J_A,6= 5.8 Hz, J_A,3= 1.5 Hz, B part additionally split

(para-C), 198.54 ppm (C-2). IR (film): ν = 3420, 2960, 2905, 2870,

˜

4

by J_B,4= 7.3 Hz, J_B,6= 5.8 Hz, J_B,3= 1.5 Hz, 5-H₂), 3.69 (ddd,

2345, 2065, 1890, 1720, 1655, 1615, 1585, 1560, 1540, 1515, 1465,

1385, 1365, 1345, 1315, 1300, 1250, 1220, 1170, 1140, 1110, 1070,

1040, 970, 840, 820 cm^–1. HRMS (CI, NH₃): calcd. for C₁₇H₂₈NO₃

294.2069 [M + NH₄]⁺; found 294.2065 (–1.4 ppm).

J_6,5–H(A)= J_6,5–H(B)= 5.9 Hz, J_6,7= 3.9 Hz, 6-H), 5.88 (ddd, J_3,4

15.9 Hz, J_3,5–H(A)

=

4

=

⁴J_3,5–H(B)= 1.4 Hz, 2-H), 6.59 (ddd, J_4,3

15.8 Hz, J_4,5–H(A)= J_4,5–H(B)= 7.3 Hz, 3-H), 7.35–7.46 (m, 4ϫ or-

tho-H, 2ϫ para-H), 7.65–7.70 ppm (m, 4ϫ meta-H). ¹³C NMR

(100 MHz, CDCl₃): δ = 17.56 and 17.99 [7-(CH₃)₂], 19.64 (C-1Ј),

26.35 (C-1), 27.15 (C₃-2Ј), 33.26 (C-6), 36.55 (C-4), 127.61 and

127.67 (4ϫ meta-C), 129.74 and 129.81 (2ϫ para-C), 133.05 (C-3),

133.90 and 134.41 (2ϫ ipso-C), 136.07 (4ϫ ortho-C), 145.73 (C-4),

(S,E)-6-(4-Methoxybenzyloxy)-7-methyloct-3-en-2-one (36b): This

compound was prepared from 33b (317 mg, 0.99 mmol) as de-

scribed for 14a. Flash chromatography (2.5ϫ14 cm, 20 mL, cyclo-

hexane/EtOAc 10:1) provided the title compound (fractions 15–29,

20

237 mg, 87%) as a colorless oil. [α] = +19.8, [α] = +27.7 (c =

436

365

198.51 ppm (C-2). IR (film): ν = 3345, 3070, 3050, 2960, 2930,

˜

0.59, CHCl₃). ¹H NMR (400 MHz, CDCl₃/CHCl₃): δ = 0.92 and

2895, 2860, 1700 1675, 1630, 1590, 1470, 1425, 1390, 1360, 1315,

1255, 1175, 1110, 1045, 985, 940, 820 cm^–1. C₂₅H₃₄O₂Si (394.62):

calcd. C 76.09, H 8.68; found C 76.01, H 8.70.

0.95 [2ϫd, J_7-Me,7= 6.8 Hz, 7-(CH₃)₂], 1.89 (qqd, J_7,8= J_7,7–Me

=

6.8 Hz, J_7,6= 3.7 Hz, 7-H), 2.21 (s, 1-H₃), AB signal (δ_A= 2.39, δ_B

= 2.44, J_AB= 14.8 Hz, A part additionally split by J_A,4= 7.5 Hz,

1-{(4S,5R)-5-[(R)-2-(Benzyloxymethoxy)pentyl]-2-phenyl-1,3,2-di-

oxaborolan-4-yl}ethanone [syn-38a; as a mixture (90:10) with 1-

{(4R,5S)-5-[(R)-2-(benzyloxymethoxy)pentyl]-2-phenyl-1,3,2-di-

oxaborolan-4-yl}ethanone (anti-38a)]: Compound 35a (102 mg,

0.37 mmol) was added at 0 °C to a stirred mixture of K₂OsO₂-

(OH)₄(1.4 mg, 1 mol-%), (DHQD)₂PHAL (14 mg, 5 mol-%),

K₃Fe(CN)₆(365 mg, 1.11 mmol, 3.0 equiv.) K₂CO₃(153 mg,

1.11 mmol, 3.0 equiv.), NaHCO₃(93 mg, 1.1 mmol, 3.0 equiv.) and

phenylboronic acid (54 mg, 0.44 mmol, 1.2 equiv.) in a 1:1 mixture

(3 mL) of tBuOH and H₂O. After the system had been kept for 2 d

at 0 °C, EtOAc (1 mL) was added and the phases were separated.

The aq. phase was extracted with EtOAc (3ϫ1 mL) and the com-

bined organic phases were dried with MgSO₄. Removal of the sol-

vent under reduced pressure and flash chromatography

(2.5ϫ15.5 cm, 10 mL, cyclohexane/EtOAc 10:1) provided the title

4

J_A,6= 5.1 Hz, J_A,3= 1.4 Hz, B part additionally split by J_B,4

=

4

7.2 Hz, J_B,6= 5.0 Hz, J_B,3= 1.5 Hz, 5-H₂), 3.27 (m_c, 6-H), 3.80

(s, OCH₃), AB signal (δ_A= 4.43, δ_B= 4.47, J_AB= 11.1 Hz,

4

OCH₂Ar), 6.10 (ddd, J_3,4= 16.0, J_3,5–H(A)

=

⁴J_3,5–H(B)= 1.4 Hz,

3-H), 6.81 ppm (ddd, J_4,3= 16.0 Hz, J_4,5–H(A)= J_4,5–H(B)= 7.3 Hz,

4-H), AAЈBBЈ signal (peaks centered at δ_A= 6.87, δ_B= 7.25, 2ϫ

ortho-H, 2ϫ meta-H). ¹³C NMR (100 MHz, CDCl₃): δ = 18.06

and 18.46 [7-(CH₃)₂], 26.78 (C-1), 31.18 (C-7), 33.92 (C-5), 55.35

(OCH₃), 71.65 (OCH₂Ar), 82.72 (C-6), 113.88 (2ϫ meta-C), 129.48

(2ϫ ortho-C), 130.70 (ipso-C), 133.09 (C-3), 145.81 (C-4), 159.30

(para-C), 198.57 ppm (C-2). IR (film): ν = 3310, 2960, 2870, 2840,

˜

2060, 1695, 1675, 1625, 1615, 1585, 1515, 1465, 1440, 1360, 1300,

1250, 1210, 1175, 1110, 1070, 1035, 980, 845, 820 cm^–1. C₁₇H₂₄O₃

(276.37): calcd. C 73.88, H 8.75; found C 73.95, H 9.04.

(R,E)-6-(tert-Butyldiphenylsilyloxy)non-3-en-2-one (37a): This com- compound (fractions 15–38, 99 mg, 68%) as a slightly yellow oil.

20

pound was prepared from 34a (916 mg, 2.08 mmol) as described Compound syn-38a (major diastereomer): [α] = –24.1, [α]

=

436

365

1

for 14a. Flash chromatography (3ϫ16.5 cm, 20 mL, cyclohexane/

EtOAc 10:1) provided the title compound (fractions 8–15, 682 mg,

–50.3 (c = 0.41, CHCl₃). H NMR (400 MHz, CDCl₃/CDCl₃): δ =

0.96 (dd, J_{5ЈЈ,4ЈЈ–H(A)}= J_{5ЈЈ,4ЈЈ–H(B)}= 7.3 Hz, 5ЈЈ-H₃), 1.36–1.52 (m,

4ЈЈ-H₂), 1.64–1.71 (m, 3ЈЈ-H₂), AB signal (δ_A= 1.96, δ_B= 2.06, J_AB

20

83%) as a colorless oil. [α] = +38.8, [α] = +40.7, [α] = +47.2,

589

578

546

20

[α]

436

= +90.0, [α]

= +169.1 (c = 1.29, CHCl₃). ¹H NMR

= 14.4 Hz, A part additionally split by J_A,2ЈЈ= 5.8 Hz, J_A,5Ј=

365

4816

www.eurjoc.org

Eur. J. Org. Chem. 2010, 4802–4822

1,3,5-Triols by Asymmetric Dihydroxylation and Deoxygenation

5.0 Hz, B part additionally split by J_B,5Ј= 7.6 Hz, J_B,2ЈЈ= 5.7 Hz,

1-{(4R,5S)-5-[(S)-2-(benzyloxymethoxy)-3-methylbutyl]-2-phenyl-

1,3,2-dioxaborolan-4-yl}ethanone (anti-38b)]: This compound was

prepared from 35b (130 mg, 0.47 mmol) as described for syn-38a.

Flash chromatography (2 ϫ14.5 cm, 10 mL, cyclohexane/EtOAc

1ЈЈ-H₂), 2.31 (s, 2-H₃), 3.92 (dddd, J_{2ЈЈ,1ЈЈ–H(A)}= J_{2ЈЈ,1ЈЈ–H(A)}

J_{2ЈЈ,3ЈЈ–H(B)}= 5.9 Hz, J_{2ЈЈ,3ЈЈ–H(B)}= 5.9 Hz, 2ЈЈ-H), 4.50 (d, J_4Ј,5Ј

=

6.4 Hz, 4Ј-H), AB signal (δ_A= 4.61, δ_B= 4.67, J_AB= 11.9 Hz,

OCH₂OCH₂Ar), 4.65 (ddd, J_{5Ј,1ЈЈ–H(B)}= 7.5 Hz, J_5Ј,4Ј= 6.5 Hz, 8:1) provided the title compound (fractions 8–28, 142 mg, 76%) as

J_{5Ј,1ЈЈ–H(A)}= 4.9 Hz, 5Ј-H), AB signal (δ_A= 4.80, δ_B= 4.83, J_ABa slightly yellow oil. Compound syn-38b (major diastereomer):

7.0 Hz, OCH₂OCH₂Ar), 7.26–7.35 (m, 2ϫ orthoЈ-H, 2ϫ metaЈ-H, [α] = –19.9, [α] = –21.1, [α] = –24.3, [α] = –46.5, [α]

=

20

589

20

578

20

546

20

436

20

365

1

paraЈ-H), 7.41 (m_c, 2ϫ meta-H), 7.52 ppm (m_c, para-H), 7.86 (m_c,

= –83.9 (c = 0.93, CHCl₃). H NMR (400 MHz, CDCl₃/CDCl₃): δ

2 ϫ ortho-H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.29 (C-5ЈЈ), = 0.96 and 1.00 [2ϫd, J_{3ЈЈ-Me,3ЈЈ}= 6.8 Hz, 3ЈЈ-(CH₃)₂], AB signal

18.50 (C-4ЈЈ), 26.28 (C-2), 36.68 (C-3ЈЈ), 41.25 (C-1ЈЈ), 69.78 (δ_A= 1.93, δ_B= 2.05, J_AB= 14.3 Hz, A part additionally split by

(OCH₂OCH₂Ar), 74.62 (C-2ЈЈ), 77.39 (C-5Ј), 86.73 (C-4Ј), 93.94 J_A,5Ј= 5.8 Hz, J_A,2ЈЈ= 4.6 Hz, B part additionally split by J_B,5Ј

=

(OCH₂OCH₂Ar), 127.71 (paraЈ-C), 127.88 (2ϫ orthoЈ-C), 128.03

(2ϫ meta-C, para-C), 128.48 (2ϫ metaЈ-C), 132.01 (ipso-C), 135.07

J_B,2ЈЈ= 6.9 Hz, 1ЈЈ-H₂), 2.05–2.14 (m, 3ЈЈ-H), 2.30 (s, 2-H₃), 3.67

(ddd, J_{2ЈЈ,1ЈЈ–H(B)}= 6.8 Hz, J_2ЈЈ,3ЈЈ= J_{2ЈЈ,1ЈЈ–H(A)}= 4.7 Hz, 2ЈЈ-H),

4.50 (d, J_4Ј,5Ј= 6.4 Hz, 4Ј-H), AB signal (δ_A= 4.63, δ_B= 4.69, J_AB

= 11.9 Hz, OCH₂OCH₂Ar), 4.68 (m_c, 5Ј-H), AB signal (δ_A= 4.81,

δ_B= 4.86, J_AB= 6.9 Hz, OCH₂OCH₂Ar), 7.27–7.37 (m, 2ϫ orthoЈ-

H, 2ϫ metaЈ-H, paraЈ-H), 7.42 (m_c, 2ϫ meta-H), 7.52 (m_c, para-

H), 7.86 ppm (m_c, 2ϫ ortho-H). ¹³C NMR (100 MHz, CDCl₃): δ

= 17.84 and 18.09 [(CH₃) _2–3ЈЈ], 26.18 (C-2), 31.29 (C-3ЈЈ), 37.83

(C-1ЈЈ), 69.89 (OCH₂OCH₂Ar), 77.82 (C-2ЈЈ), 79.96 (C-5Ј), 86.75

(C-4Ј), 94.75 (OCH₂OCH₂Ar), 127.68 (paraЈ-C), 127.84 (2ϫ or-

thoЈ-C), 128.02 (2ϫ meta-C), 128.48 (2ϫ metaЈ-C), 131.99 (para-

C), 135.07 (2ϫ ortho-C), 138.04 (ipsoЈ-C), 208.60 ppm (C-1). IR

(2ϫ ortho-C), 138.03 (ipsoЈ-C), 208.46 ppm (C-1). IR (film): ν =

˜

3455, 3030, 2960, 2935, 2875, 1720, 1605, 1500, 1440, 1405, 1360,

1315, 1255, 1210, 1170, 1100, 1040, 765, 750 cm^–1. HRMS (EI,

70 eV): calcd. for C₁₆H₂₃O₄B 290.1689 [M – OCH₂Ar]⁺; found

290.1683 (–2.2 ppm). C₂₃H₂₉BO₅(396.28): calcd. C 69.71, H 7.38;

found C 69.68, H 7.55.

1-{(4R,5S)-5-[(R)-2-(Benzyloxymethoxy)pentyl]-2-phenyl-1,3,2-di-

oxaborolan-4-yl}ethanone [anti-38a; as an inseparable mixture (92:8)

with 1-{(4S,5R)-5-[(R)-2-(benzyloxymethoxy)pentyl]-2-phenyl-1,3,2-

dioxaborolan-4-yl}ethanone (syn-38a)]: Compound 35a (104 mg,

0.38 mmol) was added at 0 °C to a stirred mixture of K₂OsO₂-

(OH)₄(1.4 mg, 1 mol-%), (DHQ)₂PHAL (15 mg, 5 mol-%),

K₃Fe(CN)₆(372 mg, 1.13 mmol, 3.0 equiv.) K₂CO₃(156 mg,

1.13 mmol, 3.0 equiv.), NaHCO₃(95 mg, 1.1 mmol, 3.0 equiv.), and

PhB(OH)₂(55 mg, 0.45 mmol, 1.2 equiv.) in a 1:1 mixture (3 mL)

of tBuOH and H₂O. After the system had been kept for 2 d at 0 °C,

EtOAc (1 mL) was added and the phases were separated. The aq.

phase was extracted with EtOAc (3ϫ1 mL). The combined organic

phases were dried with MgSO₄. Removal of the solvent under re-

duced pressure and flash chromatography (2.5ϫ17 cm, 10 mL, cy-

clohexane/EtOAc 10:1) provided the title compound (fractions 19–

44, 109 mg, 73 %) as a slightly yellow oil. Compound anti-38a

(film): ν = 3425, 3080, 3060, 3030, 3005, 2955, 2935, 2875, 1720,

˜

1605, 1500, 1455, 1440, 1405, 1380, 1360, 1305, 1250, 1205, 1165,

1100, 1030 cm^–1. C₂₃H₂₉BO₅(396.28): calcd. C 69.71, H 7.38;

found C 69.58, H 7.55.

1-{(4R,5S)-5-[(S)-2-(Benzyloxymethoxy)-3-methylbutyl]-2-phenyl-

1,3,2-dioxaborolan-4-yl}ethanone [anti-38b; as a mixture (92:8) with

1-{(4S,5R)-5-[(S)-2-(benzyloxymethoxy)-3-methylbutyl]-2-phenyl-

1,3,2-dioxaborolan-4-yl}ethanone (syn-38b)]: This compound was

prepared from 35b (126 mg, 0.46 mmol) as described for anti-38a.

Flash chromatography (2ϫ15 cm, 10 mL, cyclohexane/EtOAc 8:1)

provided the title compound (fractions 10–28, 117 mg, 65%) as a

slightly yellow oil. Compound anti-38b (major diastereomer):

20

1

[α] = –23.1, [α] = –24.0, [α] = –26.9, [α] = –39.0, [α]

(major diastereomer): [α] = –22.9 (c = 0.34, CHCl₃). H NMR

589

578

546

436

365

436

1

= –38.9 (c = 0.85, CHCl₃). H NMR (400 MHz, CDCl₃/CDCl₃): δ

= 0.93 and 0.97 [2ϫd, J_{3ЈЈ-Me,3ЈЈ}= 6.9 Hz, 3ЈЈ-(CH₃)₂], AB signal

(δ_A= 1.79, δ_B= 1.89, J_AB= 14.3 Hz, A part additionally split by

(400 MHz, CDCl₃/CDCl₃): δ = 0.94 (dd, J_{5ЈЈ,4ЈЈ–H(A)}= J_{5ЈЈ,4ЈЈ–H(B)}

= 7.3 Hz, 5ЈЈ-H₃), 1.41 (m_c, 4ЈЈ-H₂), AB signal (δ_A= 1.59, δ_B

1.66, J_AB= 13.7 Hz, A part additionally split by J_{A, 4ЈЈ–H(A)}

=

J_A,5Ј= 9.7 Hz, J_A,2ЈЈ= 2.8 Hz, B part additionally split by J_B,2ЈЈ

9.7 Hz, J_B,5Ј= 3.5 Hz, 1ЈЈ-H₂), 2.01–2.13 (m, 3-H), 2.28 (s, 2-H₃),

3.89 (ddd, J_{2ЈЈ,1ЈЈ–H(B)}= 9.7 Hz, J_2ЈЈ,3ЈЈ= 4.1 Hz, J_{2ЈЈ,1ЈЈ–H(A)}

=

8.6 Hz, J_A,2ЈЈ= J_{A, 4ЈЈ–H(B)}= 6.5 Hz, B part additionally split by

J_{B, 4ЈЈ–H(B)}= 8.4 Hz, J_{B, 4ЈЈ–H(A)}= 7.9 Hz, J_{B, 2ЈЈ}= 5.4 Hz, 3ЈЈ-H₂),

AB signal (δ_A= 1.87, δ_B= 1.95, J_AB= 14.2 Hz, A part additionally

split by J_A,5Ј= 9.5 Hz, J_A,2ЈЈ= 3.7 Hz, B part additionally split by

J_B,2ЈЈ= 9.0 Hz, J_B,5Ј= 3.9 Hz, 1ЈЈ-H₂), 2.29 (s, 2-H₃), 4.03 (dddd,

J_{2ЈЈ,1ЈЈ–H(B)}= 9.1 Hz, J_{2ЈЈ,3ЈЈ–H(A)}= 6.1 Hz, J_{2ЈЈ,3ЈЈ–H(B)}= 5.6 Hz,

J_{2ЈЈ,1ЈЈ–H(A)}= 3.5 Hz, 2ЈЈ-H), 4.44 (d, J_4Ј,5Ј= 6.7 Hz, 4Ј-H), AB sig-

nal (δ_A= 4.65, δ_B= 4.69, J_AB= 11.7 Hz, OCH₂OCH,Ar), 4.71

(ddd, J_{5Ј,1ЈЈ–H(A)}= 9.4 Hz, J_5Ј,4Ј= 6.7, J_{5Ј,1ЈЈ–H(B)}= 3.8 Hz, 5Ј-H),

AB signal (δ_A= 4.86, δ_B= 4.89 Hz, J_AB= 7.0, OCH₂OCH₂Ar),

7.26–7.43 (m, 2ϫ ortho-H, 2ϫ orthoЈ-H, 2ϫ metaЈ-H, paraЈ-H),

7.52 (m_c, para-H), 7.85 ppm (m_c, 2 ϫ meta-H). ¹³C NMR

(100 MHz, CDCl₃): δ = 14.33 (C-5ЈЈ), 18.18 (C-4ЈЈ), 26.18 (C-2),

37.11 (C-3ЈЈ), 42.41 (C-1ЈЈ), 69.76 (OCH₂OCH₂Ar), 74.08 (C-2ЈЈ),

77.19 (C-5Ј), 86.77 (C-4Ј), 93.91 (OCH₂OCH₂Ar), 127.72 (paraЈ-

C), 127.93 (2ϫ orthoЈ-C), 128.00 (2ϫ meta-C, para-C), 128.49 (2ϫ

metaЈ-C), 131.99 (ipso-C), 135.09 (2ϫ ortho-C), 138.03 (ipsoЈ-C),

=

2.9 Hz, 2ЈЈ-H), 4.46 (d, J_4Ј,5Ј= 6.7 Hz, 4Ј-H), 4.68 (s, OCH₂O-

CH₂Ar), 4.71 (ddd, J_{5Ј,1ЈЈ–H(A)}= 9.9 Hz, J_5Ј,4Ј= 6.5 Hz, J_{5Ј,1ЈЈ–H(B)}

= 3.4 Hz, 5Ј-H), 4.89 (s, OCH₂OCH₂Ar), 7.25–7.44 (m, 2ϫ orthoЈ-

H, 2ϫ metaЈ-H, paraЈ-H), 7.42 (m_c, 2ϫ meta-H), 7.52 (m_c, para-

H), 7.86 ppm (m_c, 2ϫ ortho-H). ¹³C NMR (100 MHz, CDCl₃): δ

= 16.91 and 18.26 [(CH₃) _2–3ЈЈ], 26.11 (C-2), 31.18 (C-3ЈЈ), 38.05

(C-1ЈЈ), 69.84 (OCH₂OCH₂Ar), 77.37 (C-2ЈЈ), 79.91 (C-5Ј), 86.82

(C-4Ј), 94.62 (OCH₂OCH₂Ar), 127.69 (paraЈ-C_r), 127.84 (2ϫ or-

thoЈ-C), 127.99 and 128.02 (2ϫ meta-C), 128.48 (2 ϫ metaЈ-C),

131.97 (ipso-C), 135.07 (para-C), 135.09 (2 ϫ ortho-C), 138.02

(ipsoЈ-C), 208.12 ppm (C-1). IR (film): ν = 3455, 3060, 3030, 2960,

˜

2935, 2875, 1720, 1605, 1500, 1455, 1440, 1405, 1360, 1315, 1305,

1255, 1210, 1170, 1100, 1040, 1030, 975 cm^–1. C₂₃H₂₉BO₅(396.28):

calcd. C 69.71, H 7.38; found C 69.49, H 7.63.

208.06 ppm (C-1). IR (film): ν = 3425, 3060, 3030, 2960, 2935,

˜

1-{(4S,5R)-5-[(R)-2-(4-Methoxybenzyloxy)pentyl]-2-phenyl-1,3,2-di-

oxaborolan-4-yl}ethanone [syn-39a; as a mixture (92:8) with 1-

{(4R,5S)-5-[(R)-2-(4-methoxybenzyloxy)pentyl]-2-phenyl-1,3,2-di-

oxaborolan-4-yl}ethanone (anti-39a)]: This compound was prepared

from 36a (85 mg, 0.31 mmol) as described for syn-38a. Flash

2875, 1720, 1605, 1500, 1455, 1440, 1405, 1360, 1305, 1210, 1170,

1100, 1040, 910, 765, 750 cm^–1. HRMS (EI, 70 eV): calcd. for

C₁₆H₂₃O₄B 290.1689 [M – OCH₂Ar]⁺; found 290.1685 (–1.5 ppm).

C₂₃H₂₉BO₅(396.28): calcd. C 69.71, H 7.38; found C 69.57, H 7.45.

1-{(4S,5R)-5-[(S)-2-(Benzyloxymethoxy)-3-methylbutyl]-2-phenyl- chromatography (2.5ϫ16 cm, 10 mL, cyclohexane/EtOAc 9:1) pro-

1,3,2-dioxaborolan-4-yl}ethanone [syn-38b; as a mixture (91:9) with vided the title compound (fractions 13–36, 94 mg, 77 %) as a

Eur. J. Org. Chem. 2010, 4802–4822

www.eurjoc.org

4817

P. Walleser, R. Brückner

FULL PAPER

slightly yellow oil. Compound syn-39a (major diastereomer):

prepared from 36b (84 mg, 0.30 mmol) as described for syn-38a.

Flash chromatography (2.5ϫ16 cm, 10 mL, cyclohexane/EtOAc

20

[α] = –30.8, [α] = –32.8, [α] = –38.0, [α] = –72.2, [α]

= –133.3 (c = 0.48, CHCl₃). H NMR (400 MHz, CDCl₃/CDCl₃): 9:1) provided the title compound (fractions 14–39, 80 mg, 66%) as

δ = 0.95 (dd, J_{5ЈЈ,4ЈЈ–H(A)}= J_{5ЈЈ,4ЈЈ–H(B)}= 7.3 Hz, 5ЈЈ-H₃), 1.34–1.50 a slightly yellow oil. Compound syn-39b (major diastereomer):

589

578

546

436

365

1

20

(m, 4ЈЈ-H₂), 1.54–1.71 (m, 3ЈЈ-H₂), AB signal (δ_A= 1.94, δ_B= 2.07, [α] = –52.2, [α] = –55.1, [α] = –63.1, [α] = –115.2, [α]

J_AB= 14.2 Hz, A part additionally split by J_A,2ЈЈ= J_A,5Ј= 5.5 Hz,

B part additionally split by J_B,5Ј= J_B,2ЈЈ= 6.6 Hz, 1ЈЈ-H₂), 2.30 (s,

589

578

546

436

365

1

= –203.7 (c = 0.77, CHCl₃). H NMR (400 MHz, CDCl₃/CDCl₃):

δ = 0.95 and 0.96 [2ϫd, J_{3ЈЈ-Me,3ЈЈ}= 6.8 Hz, 3ЈЈ-(CH₃)₂], AB signal

(δ_A= 1.90, δ_B= 2.03, J_AB= 14.4 Hz, A part additionally split by

2-H₃), 3.68 (m_c, 2ЈЈ-H), 3.79 (s, OCH₃), AB signal (δ_A= 4.42, δ_B

=

4.46, J_AB= 10.9 Hz, OCH₂Ar), 4.57 (d, J_4Ј,5Ј= 6.4 Hz, 4Ј-H), 4.67 J_A,5Ј= 6.5 Hz, J_A,2ЈЈ= 3.8 Hz, B part additionally split by J_B,2ЈЈ

=

(m_c, approximately interpretable as ddd, J_{5Ј,1ЈЈ–H(B)}= J_5Ј,4Ј

6.2 Hz, J_{5Ј,1ЈЈ–H(A)}= 6.0 Hz, 5Ј-H), AAЈBBЈ signal (peaks centered

at δ_A= 6.86 and δ_B= 7.27, 2ϫ orthoЈ-H, 2ϫ metaЈ-H), 7.42 (m_c,

=

7.7 Hz, J_B,5Ј= 5.9 Hz, 1ЈЈ-H₂), 2.04–2.14 (m, 3ЈЈ-H), 2.30 (s, 2-H₃),

3.45 (ddd, J_{2ЈЈ,1ЈЈ–H(B)}= 7.7 Hz, J_2ЈЈ,3ЈЈ= 4.7 Hz, J_{2ЈЈ,1ЈЈ–H(A)}

3.8 Hz, 2ЈЈ-H), 3.80 (s, OCH₃), AB signal (δ_A= 4.42, δ_B= 4.48,

=

2ϫ meta-H), 7.53 (m_c, para-H), 7.86 ppm (m_c, 2ϫ ortho-H). ¹³C J_AB= 10.7 Hz, OCH₂Ar), 4.58 (d, J_4Ј,5Ј= 6.3 Hz, 4Ј-H), 4.70 (ddd,

NMR (100 MHz, CDCl₃): δ = 14.32 (C-5ЈЈ), 18.48 (C-4ЈЈ), 26.24 J_{5Ј,1ЈЈ–H(A)}= J_{5Ј,1ЈЈ–H(B)}= J_5Ј,4Ј= 6.2 Hz, 5Ј-H), AAЈBBЈ signal

(C-2), 36.12 (C-3ЈЈ), 40.61 (C-1ЈЈ), 55.35 (OCH₃), 70.65 (OCH₂Ar),

75.07 (C-2ЈЈ), 77.47 (C-5Ј), 86.60 (C-4Ј), 113.85 (2 ϫ metaЈ-C), H), 7.42 (m_c, 2ϫ meta-H), 7.53 (m_c, para-H), 7.87 ppm (m_c, 2ϫ

128.02 (2ϫ meta-C), 129.53 (ipsoЈ-C, 2ϫ orthoЈ-C), 130.88 (ipso-

ortho-H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.38 and 18.46

C), 131.97 (para-C), 135.07 (2 ϫ ortho-C), 159.22 (paraЈ-C), [(CH₃)_2–3ЈЈ], 26.16 (C-2), 30.27 (C-3ЈЈ), 36.74 (C-1ЈЈ), 55.33

(peaks centered at δ_A= 6.87 and δ_B= 7.29, 2ϫ orthoЈ-H, 2ϫ metaЈ-

208.45 ppm (C-1). IR (film): ν = 3425, 2955, 2935, 2870, 1720,

(OCH₃), 71.19 (OCH₂Ar), 77.94 (C-2ЈЈ), 79.99 (C-5Ј), 86.60 (C-4Ј),

113.81 (2ϫ metaЈ-C), 128.02 (2ϫ meta-C), 129.50 (ipsoЈ-C, 2ϫ

˜

1605, 1585, 1515, 1465, 1440, 1405, 1360, 1300, 1250, 1210, 1175,

1100, 1035, 825, 760 cm^–1. HRMS (EI, 70 eV): calcd. for orthoЈ-C), 131.02 (ipso-C), 131.96 (para-C), 135.07 (2ϫ ortho-C),

C₁₅H₂₁O₃B 260.1584 [M – CH₂C₆H₄OCH₃]⁺; found 260.1580

(–1.5 ppm). C₂₃H₂₉BO₅(396.28): calcd. C 69.71, H 7.38; found C

69.73, H 7.56.

159.18 (paraЈ-C), 208.67 ppm (C-1). IR (film): ν = 3430, 2960,

˜

2930, 2870, 1720, 1610, 1605, 1585, 1515, 1500, 1465, 1440, 1405,

1360, 1300, 1250, 1210, 1175, 1145, 1095, 1035, 820 cm^–1

.

C₂₃H₂₉BO₅(396.28): calcd. C 69.71, H 7.38; found C 69.60, H 7.58.

1-{(4R,5S)-5-[(R)-2-(4-Methoxybenzyloxy)pentyl]-2-phenyl-1,3,2-di-

oxaborolan-4-yl}ethanone [anti-39a; as a mixture (92:8) with 1- 1-{(4R,5S)-5-[(S)-2-(4-Methoxybenzyloxy)-3-methylbutyl]-2-phenyl-

{(4S,5R)-5-[(R)-2-(4-methoxybenzyloxy)pentyl]-2-phenyl-1,3,2-di-

oxaborolan-4-yl}ethanone (syn-39a)]: This compound was prepared

from 36a (81 mg, 0.29 mmol) as described for anti-38a. Flash

1,3,2-dioxaborolan-4-yl}ethanone [anti-39b; as a mixture (92:8) with

1-{(4S,5R)-5-[(S)-2-(4-methoxybenzyloxy)-3-methylbutyl]-2-phenyl-

1,3,2-dioxaborolan-4-yl}ethanone (syn-39b)]: This compound was

chromatography (2.5ϫ15 cm, 10 mL, cyclohexane/EtOAc 9:1) pro- prepared from 36b (86 mg, 0.31 mmol) as described for anti-38a.

vided the title compound (fractions 11–37, 95 mg, 82 %) as a

slightly yellow oil. Compound anti-39a (major diastereomer):

Flash chromatography (2.5ϫ15 cm, 10 mL, cyclohexane/EtOAc

9:1) provided the title compound (fractions 18–40, 73 mg, 59%) as

a slightly yellow oil. Compound anti-39b (major diastereomer):

20

[α] = –28.8, [α] = –30.3, [α] = –34.4, [α] = –57.2, [α]

= –82.3 (c = 0.71, CHCl₃). H NMR (400 MHz, CDCl₃/CDCl₃): δ [α] = –40.0, [α] = –41.5, [α] = –47.1, [α] = –78.0, [α]

589

578

546

436

365

1

20

589

578

546

436

365

1

= 0.95 (dd, J_{5ЈЈ,4ЈЈ–H(A)}= J_{5ЈЈ,4ЈЈ–H(B)}= 7.3 Hz, 5ЈЈ-H₃), 1.41 (m_c, = –112.0 (c = 1.32, CHCl₃). H NMR (400 MHz, CDCl₃/CDCl₃):

4ЈЈ-H₂), AB signal (δ_A= 1.56, δ_B= 1.65, J_AB= 13.8 Hz, A part

additionally split by J_{A,4ЈЈ–H(A)}= 8.7 Hz, J_A,2ЈЈ= J_{A,4ЈЈ–H(B)}

6.4 Hz, B part additionally split by J_{B,4ЈЈ–H(B)}= 8.1 Hz, J_{B,4ЈЈ–H(A)}

= 7.9 Hz, J_B,2ЈЈ= 5.6 Hz, 3ЈЈ-H₂), AB signal (δ_A= 1.87, δ_B= 1.94, 8.1 Hz, J_B,5Ј= 5.2 Hz, 1ЈЈ-H₂), 2.00–2.10 (m, 3ЈЈ-H), 2.25 (s, 2-H₃),

J_AB= 14.2 Hz, A part additionally split by J_A,5Ј= 8.6 Hz, J_A,2ЈЈ3.62 (ddd, J_{2ЈЈ,1ЈЈ–H(B)}= 8.6 Hz, J_2ЈЈ,3ЈЈ= 4.4 Hz, J_{2ЈЈ,1ЈЈ–H(A)}

3.7 Hz, B part additionally split by J_B,2ЈЈ= 9.1 Hz, J_B,5Ј= 4.9 Hz, 4.0 Hz, 2ЈЈ-H), 3.79 (s, OCH₃), AB signal (δ_A= 4.46, δ_B= 4.59,

1ЈЈ-H₂), 2.26 (s, 2-H₃), 3.77 (dddd, J_{2ЈЈ,1ЈЈ–H(B)}= 9.1 Hz, J_{2ЈЈ,3ЈЈ–H(A)}J_AB= 10.9 Hz, OCH₂Ar), 4.52 (d, J_4Ј,5Ј= 6.4 Hz, 4Ј-H), 4.70 (ddd,

δ = 0.95 and 0.96 [2ϫd, J_{3ЈЈ-Me,3ЈЈ}= 6.8 Hz, 3ЈЈ-(CH₃)₂], AB signal

=

(δ_A= 1.81, δ_B= 1.86, J_AB= 14.2 Hz, A part additionally split by

J_A,5Ј= 8.1 Hz, J_A,2ЈЈ= 4.0 Hz, B part additionally split by J_B,2ЈЈ

=

= J_{2ЈЈ,3ЈЈ–H(B)}= 5.7 Hz, J_{2ЈЈ,1ЈЈ–H(A)}= 3.4 Hz, 2ЈЈ-H), 3.80 (s, OCH₃),

AB signal (δ_A= 4.45, δ_B= 4.56, J_AB= 10.9 Hz, OCH₂Ar), 4.49 (d,

J_4Ј,5Ј= 6.6 Hz, 4Ј-H), 4.71 (ddd, J_{5Ј,1ЈЈ–H(A)}= 8.5 Hz, J_5Ј,4Ј= 6.5 Hz,

J_{5Ј,1ЈЈ–H(A)}= 8.2 Hz, J_5Ј,4Ј= 6.4 Hz, J_{5Ј,1ЈЈ–H(B)}= 5.3 Hz, 5Ј-H),

AAЈBBЈ signal (peaks centered at δ_A= 6.88 and δ_B= 7.28, 2ϫ

orthoЈ-H, 2ϫ metaЈ-H), 7.42 (m_c, 2ϫ meta-H), 7.53 (m_c, para-H),

7.86 ppm (m_c, 2ϫ ortho-H). ¹³C NMR (100 MHz, CDCl₃): δ =

17.02 and 18.49 [(CH₃)_2–3ЈЈ], 26.20 (C-2), 30.47 (C-3ЈЈ), 37.88 (C-

J_{5Ј,1ЈЈ–H(B)}= 4.8 Hz, 5Ј-H), AAЈBBЈ signal (peaks centered at δ_A

=

6.88 and δ_B= 7.28, 2ϫ orthoЈ-H, 2ϫ metaЈ-H), 7.42 (m_c, 2ϫ meta-

H), 7.52 (m_c, para-H), 7.85 ppm (m_c, 2 ϫ ortho-H). ¹³C NMR 1ЈЈ), 55.34 (OCH₃), 71.76 (OCH₂Ar), 77.34 (C-2ЈЈ), 80.10 (C-5Ј),

(100 MHz, CDCl₃): δ = 14.38 (C-5ЈЈ), 18.27 (C-4ЈЈ), 26.25 (C-2), 86.75 (C-4Ј), 113.82 (2ϫ metaЈ-C), 127.98 (2ϫ meta-C), 129.37

36.50 (C-3ЈЈ), 42.10 (C-1ЈЈ), 55.36 (OCH₃), 70.99 (OCH₂Ar), 75.26 (ipsoЈ-C, 2ϫ orthoЈ-C), 131.13 (ipso-C), 131.92 (para-C), 135.05

(C-2ЈЈ), 77.47 (C-5Ј), 86.72 (C-4Ј), 113.84 (2ϫ metaЈ-C), 127.99 (2ϫ ortho-C), 159.17 (paraЈ-C), 208.65 ppm (C-1). IR (film): ν =

˜

(2 ϫ meta-C), 129.44 (ipsoЈ-C, 2 ϫ orthoЈ-C), 130.99 (ipso-C),

131.93 (para-C), 135.06 (2 ϫ ortho-C), 159.22 (paraЈ-C),

3430, 2960, 2930, 2870, 2875, 1720, 1610, 1605, 1585, 1515, 1500,

1465, 1440, 1405, 1380, 1360, 1318, 1300, 1250, 1205, 1175, 1095,

1035, 985, 820 cm^–1. C₂₃H₂₉BO₅(396.28): calcd. C 69.71, H 7.38;

found C 69.59, H 7.62.

207.71 ppm (C-1). IR (film): ν = 3430, 3000, 2955, 2930, 2870,

˜

2835, 1720, 1605, 1585, 1515, 1465, 1440, 1360, 1300, 1250, 1210,

1175, 1095, 1035, 825, 760 cm^–1. HRMS (EI, 70 eV): calcd. for

C₁₅H₂₁O₃B 260.1584 [M – CH₂C₆H₄OCH₃]⁺; found 260.1577

(–2.6 ppm). C₂₃H₂₉BO₅(396.28): calcd. C 69.71, H 7.38; found C

69.73, H 7.66.

1-{(4S,5R)-5-[(R)-2-(tert-Butyldiphenylsilyloxy)pentyl]-2-phenyl-

1,3,2-dioxaborolan-4-yl}ethanone [syn-40a; as a mixture (76:24) with

1-{(4R,5S)-5-[(R)-2-(tert-butyldiphenylsilyloxy)-pentyl]-2-phenyl-

1,3,2-dioxaborolan-4-yl}ethanone (anti-40a)]: This compound was

prepared from 37a (150 mg, 0.38 mmol) as described for syn-38a.

Flash chromatography (2.5ϫ17 cm, 10 mL, cyclohexane/EtOAc

1-{(4S,5R)-5-[(S)-2-(4-Methoxybenzyloxy)-3-methylbutyl]-2-phenyl-

1,3,2-dioxaborolan-4-yl}ethanone [syn-39b; as a mixture (93:7) with

1-{(4R,5S)-5-[(S)-2-(4-methoxybenzyloxy)-3-methylbutyl]-2-phenyl- 10:1) provided the title compound (fractions 8–26, 160 mg, 82%)

1,3,2-dioxaborolan-4-yl}ethanone (anti-39b)]: This compound was as a slightly yellow oil. Compound syn-40a (major diastereomer):

4818

www.eurjoc.org

Eur. J. Org. Chem. 2010, 4802–4822

1,3,5-Triols by Asymmetric Dihydroxylation and Deoxygenation

20

[α] = –10.9, [α] = –11.3, [α] = –13.0, [α] = –26.2, [α]

6.8 Hz, 3ЈЈ-(CH₃)₂], 1.07 (s, 2ЈЈЈ-H₉), 1.64–1.75 (m, 3ЈЈ-H), AB sig-

= –47.6 (c = 0.75, CHCl₃). H NMR (400 MHz, CDCl₃/CDCl₃): δ nal (δ_A= 1.79, δ_B= 1.91, J_AB= 14.1 Hz, A part additionally split

= 0.79 (dd, J_{5ЈЈ,4ЈЈ–H(A)}= J_{5ЈЈ,4ЈЈ–H(B)}= 7.3 Hz, 5ЈЈ-H₃), 1.06 (s, 2ЈЈЈ- J_A,5Ј= 9.3 Hz, J_A,2ЈЈ= 4.7 Hz, B part additionally split J_B,2ЈЈ

589

578

546

436

365

1

=

H₉), 1.11–1.60 (m, 3ЈЈ-H₂, 4ЈЈ-H₂), AB signal (δ_A= 1.87, δ_B= 1.91,

J_AB= 14.1 Hz, A part additionally split by J_A,5Ј= J_A,2ЈЈ= 4.7 Hz,

B part additionally split by J_B,2ЈЈ= 6.3 Hz, J_B,5Ј= 5.0 Hz, 1ЈЈ-H₂),

7.8 Hz, J_B,5Ј= 4.0 Hz, 1ЈЈ-H₂), 2.20 (s, 2-H₃), 3.94 (ddd, J_{2ЈЈ,1ЈЈ–H(B)}

= 7.8 Hz, J_{2ЈЈ,1ЈЈ–H(A)}= 4.6 Hz, J_2ЈЈ,3ЈЈ= 3.2 Hz, 2ЈЈ-H), 4.17 (d,

J_4Ј,5Ј= 6.3 Hz, 4Ј-H), 4.42 (ddd, J_{5Ј,1ЈЈ–H(A)}= 9.2 Hz, J_5Ј,4Ј= 6.3,

2.27 (s, 2-H₃), 4.07 (dddd, J_{2ЈЈ,1ЈЈ–H(B)}= J_{2ЈЈ,3ЈЈ–H(A)}= 6.0 Hz, J_{5Ј,1ЈЈ–H(B)}= 4.0 Hz, 5Ј-H), 7.27–7.47 (m, 2ϫ meta-H, 4ϫ orthoЈ-

J_{2ЈЈ,3ЈЈ–H(B)}= 5.7 Hz, J_{2ЈЈ,1ЈЈ–H(A)}= 5.1 Hz, 2ЈЈ-H), 4.33 (d, J_4Ј,5ЈH, 2ϫ paraЈ-H), 7.48–7.54 (m, para-H), 7.65–7.77 ppm (m, 2ϫ

6.4 Hz, 4Ј-H), 4.61 (ddd, J_{5Ј,1ЈЈ–H(A)}= 7.9 Hz, J_5Ј,4Ј= 6.2 Hz, ortho-H, 4ϫ metaЈ-H). ¹³C NMR (100 MHz, CDCl₃): δ = 16.36

=

J_{5Ј,1ЈЈ–H(B)}= 5.1 Hz, 5Ј-H), 7.30–7.47 (m, 2ϫ meta-H, 4ϫ orthoЈ-

H, 2ϫ paraЈ-H), 7.52 (m_c, para-H), 7.66–7.80 ppm (m_c, 2ϫ ortho-

and 19.23 [(CH₃)_2–3ЈЈ], 19.67 (C-2), 26.10 (C-3ЈЈ), 27.20 (C₃-2ЈЈЈ),

31.76 (C-1ЈЈЈ), 41.33 (C-1ЈЈ), 74.38 (C-5Ј), 77.00 (C-2ЈЈ), 86.75 (C-

H, 4ϫ metaЈ-H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.19 (C-5ЈЈ), 4Ј), 127.51 and 127.56 (4ϫ metaЈ-C), 127.89 (2ϫ paraЈ-C), 129.55

18.13 (C-4ЈЈ), 19.41 (C-2), 26.16 (C-3ЈЈ), 27.13 (C₃-2ЈЈЈ), 38.19 (C- and 129.64 (2ϫ meta-C), 131.90 (para-C), 135.08 (4ϫ orthoЈ-C),

1ЈЈЈ), 43.20 (C-1ЈЈ), 70.14 (C-5Ј), 77.04 (C-2ЈЈ), 86.80 (C-4Ј), 127.58

and 127.61 (4ϫ metaЈ-C), 127.94 (2ϫ paraЈ-C), 129.64 (2ϫ meta-

C), 131.92 (para-C), 134.32 (ipso-C), 134.56 (2ϫ ipsoЈ-C), 135.07

(4ϫ orthoЈ-C), 135.97 (2ϫ ortho-C), 208.09 ppm (C-1). IR (film):

136.08 (ipso-C), 136.11 (2 ϫ ipsoЈ-C), 136.24 (2 ϫ ortho-C),

208.15 ppm (C-1). IR (film): ν = 3455, 3070, 3050, 2960, 2930,

˜

2860, 1965, 1900, 1825, 1720, 1660, 1605, 1590, 1500, 1470, 1460,

1440, 1425, 1375, 1360, 1315, 1205, 1155, 1110, 1070, 1040, 1005,

935, 895, 820, 805, 765, 740, 700 cm^–1. C₃₁H₃₉BO₄Si (514.54):

calcd. C 72.36, H 7.64; found C 72.20, H 7.70.

ν = 3460, 3070, 3050, 2960, 2930, 2860, 1965, 1900, 1825, 1720,

˜

1605, 1590, 1500, 1470, 1460, 1440, 1425, 1375, 1360, 1315, 1255,

1205, 1155, 1110, 1070, 1040, 1005, 895, 820, 805, 765, 740,

700 cm^–1. C₃₁H₃₉BO₄Si (514.54): calcd. C 72.36, H 7.64; found C

72.09, H 7.79.

1-{(4R,5S)-5-[(S)-2-(tert-Butyldiphenylsilyloxy)-3-methylbutyl]-2-

phenyl-1,3,2-dioxaborolan-4-yl}ethanone [anti-40b; as a mixture

(94:6) with 1-{(4S,5R)-5-[(R)-2-(tert-butyldiphenylsilyloxy)3-meth-

ylbutyl]-2-phenyl-1,3,2-dioxaborolan-4-yl}ethanone (syn-40b)]: This

compound was prepared from 37b (134 mg, 0.34 mmol) as de-

scribed for anti-38b. Flash chromatography (2ϫ15 cm, 10 mL, cy-

clohexane/EtOAc 20:1) provided the title compound (fractions 15–

1-{(4R,5S)-5-[(R)-2-(tert-Butyldiphenylsilyloxy)pentyl]-2-phenyl-

1,3,2-dioxaborolan-4-yl}ethanone [anti-40a; as a mixture (89:11)

with 1-{(4S,5R)-5-[(R)-2-(tert-butyldiphenylsilyloxy)pentyl]-2-

phenyl-1,3,2-dioxaborolan-4-yl}ethanone (syn-40a)]: This compound

was prepared from 37a (150 mg, 0.38 mmol) as described for anti-

38a. Flash chromatography (2.5 ϫ 17 cm, 10 mL, cyclohexane/

EtOAc 10:1) provided the title compound (fractions 9–29, 119 mg,

61 %) as a slightly yellow oil. Compound anti-40a (major dia-

29, 70 mg, 40%) as a slightly yellow oil. Compound anti-40a (major

20

diastereomer): [α]

= –16.0 (c = 1.27, CHCl₃). ¹H NMR

365

(400 MHz, CDCl₃/CDCl₃): δ = 0.76 and 0.94 [2ϫd, J_{3ЈЈ-Me,3ЈЈ}

6.9 Hz, 3ЈЈ-(CH₃)₂], 1.09 (s, 2ЈЈЈ-H₉), AB signal (δ_A= 1.68, δ_B

=

20

1.82, J_AB= 14.0 Hz, A part additionally split by J_A,5Ј= 10.3 Hz,

J_A,2ЈЈ= 3.5 Hz, B part additionally split by J_B,2ЈЈ= 8.8 Hz, J_B,5Ј

stereomer): [α]

= –17.3, [α]

= –18.0, [α]

= –20.4, [α]

=

589

578

546

436

–32.5, [α] = –51.0 (c = 0.85, CHCl₃). ¹H NMR (400 MHz, CDCl₃/

20

=

365

3.3 Hz, 1ЈЈ-H₂), 1.80–1.93 (m, 3ЈЈ-H), 2.16 (s, 2-H₃), 3.99 (ddd,

J_{2ЈЈ,1ЈЈ–H(B)}= 8.8 Hz, J_{2ЈЈ,1ЈЈ–H(A)}= J_2ЈЈ,3ЈЈ= 3.2 Hz, 2ЈЈ-H), 4.17 (d,

CDCl₃): δ = 0.71 (dd, J_{5ЈЈ,4ЈЈ–H(A)}= J_{5ЈЈ,4ЈЈ–H(B)}= 7.3 Hz, 5ЈЈ-H₃),

1.06 (s, 2ЈЈЈ-H₉), 1.08–1.67 (m, 3ЈЈ-H₂, 4ЈЈ-H₂), AB signal (δ_A= 1.79,

δ_B= 1.88, J_AB= 13.9 Hz, A part additionally split by J_A,5Ј= 9.7 Hz,

J_4Ј,5Ј= 7.1 Hz, 4Ј-H), 4.48 (ddd, J_{5Ј,1ЈЈ–H(A)}= 10.2 Hz, J_5Ј,4Ј

=

7.0 Hz, J_{5Ј,1ЈЈ–H(B)}= 3.3 Hz, 5Ј-H), 7.34–7.48 (m, 2ϫ meta-H, 4ϫ

orthoЈ-H, 2ϫ paraЈ-H), 7.50 (m_c, para-H), 7.66–7.77 ppm (m, 2ϫ

ortho-H, 4ϫ metaЈ-H). ¹³C NMR (100 MHz, CDCl₃): δ = 16.68

and 17.83 [(CH₃)_2–3ЈЈ], 19.66 (C-2), 25.74 (C-3ЈЈ), 27.22 (C₃-2ЈЈЈ),

33.30 (C-1ЈЈЈ), 39.61 (C-1ЈЈ), 73.99 (C-5Ј), 77.00 (C-2ЈЈ), 86.93 (C-

4Ј), 127.57 (4ϫ metaЈ-C), 127.90 (2ϫ paraЈ-C), 129.55 and 129.69

(2ϫ meta-C), 131.89 (C-4ЈЈ), 134.12 (ipso-C), 134.56 (2ϫ ipsoЈ-C),

135.08 (4ϫ orthoЈ-C), 136.25 (2ϫ ortho-C), 207.82 ppm (C-1). IR

J_A,2ЈЈ= 4.0 Hz, B part additionally split by J_B,2ЈЈ= 8.3 Hz, J_B,5Ј

3.7 Hz, 1ЈЈ-H₂), 2.21 (s, 2-H₃), 4.10 (dddd, J_{2ЈЈ,1ЈЈ–H(B)}= 8.5 Hz,

J_{2ЈЈ,3ЈЈ–H(A)}= J_{2ЈЈ,3ЈЈ–H(B)}= 5.2 Hz, J_{2ЈЈ,1ЈЈ–H(A)}= 4.0 Hz, 2ЈЈ-H), 4.19

=

(d, J_4Ј,5Ј= 7.0 Hz, 4Ј-H), 4.60 (ddd, J_{5Ј,1ЈЈ–H(A)}= 9.7 Hz, J_5Ј,4Ј

=

7.0 Hz, J_{5Ј,1ЈЈ–H(B)}= 3.7 Hz, 5Ј-H), 7.29–7.47 (m, 2ϫ meta-H 4ϫ

orthoЈ-H, 2ϫ paraЈ-H), 7.51 (m_c, para-H), 7.65–7.79 ppm (m_c, 2ϫ

ortho-H, 4ϫ metaЈ-H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.06 (C-

5ЈЈ), 17.70 (C-4ЈЈ), 19.57 (C-2), 25.88 (C-3ЈЈ), 27.16 (C₃-2ЈЈЈ), 39.61

(C-1ЈЈЈ), 44.13 (C-1ЈЈ), 69.73 (C-5Ј), 77.02 (C-2ЈЈ), 86.83 (C-4Ј),

127.57 and 127.61 (4ϫ metaЈ-C), 127.95 (2ϫ paraЈ-C), 129.63 (2ϫ

meta-C), 131.92 (para-C), 134.27 (ipso-C), 134.46 (2 ϫ ipsoЈ-C),

135.09 (4 ϫ orthoЈ-C), 136.09 and 136.13 (2ϫ ortho-C), 207.89 ppm

(film): ν = 3445, 3070, 3050, 2960, 2930, 2860, 1965, 1900, 1825,

˜

1720, 1600, 1590, 1500, 1470, 1460, 1440, 1425, 1380, 1360, 1315,

1240, 1205, 1155, 1110, 1040, 1005, 940, 910, 820, 760, 740,

700 cm^–1. C₃₁H₃₉BO₄Si (514.54): calcd. C 72.36, H 7.64; found C

71.12, H 7.94.

(C-1). IR (film): ν = 3465, 3070, 3050, 2960, 2930, 2855, 1965, 1900,

˜

1825, 1720, 1605, 1590, 1500, 1470, 1460, 1440, 1425, 1380, 1360,

1315, 1240, 1205, 1155, 1110, 1040, 1005, 1000, 940, 910, 820, 805,

760, 740, 700 cm^–1. C₃₁H₃₉BO₄Si (514.54): calcd. C 72.36, H 7.64;

found C 72.07, H 7.88.

Preparation of SmBr₂in THF: 1,1,2,2-Tetrabromoethane (354 mg,

1.02 mmol, 0.5 equiv.) was dissolved in THF (21 mL) and degassed

at –78 °C. It was cannulated onto Sm powder (40 mesh, 308 mg,

2.05 mmol). After stirring at room temp. for 16 h, we obtained a

black suspension. Its concentration in SmBr₂was assumed to be

0.1 . Because of the low stability of this solution it was prepared

immediately before use.

1-{(4S,5R)-5-[(S)-2-(tert-Butyldiphenylsilyloxy)-3-methylbutyl]-2-

phenyl-1,3,2-dioxaborolan-4-yl}ethanone [syn-40b; as a mixture

(71:29) with 1-{(4R,5S)-5-[(R)-2-(tert-butyldiphenylsilyloxy)3-meth-

ylbutyl]-2-phenyl-1,3,2-dioxa-borolan-4-yl}ethanone (anti-40b)]: (4R,6R)-4-Hydroxy-6-(4-methoxybenzyloxy)nonan-2-one [syn-41; as

This compound was prepared from 37b (135 mg, 0.34 mmol) as

described for syn-38b. Flash chromatography (2.5ϫ17 cm, 10 mL,

cyclohexane/EtOAc 20:1) provided the title compound (fractions

a mixture (91:9) with (4S,6R)-4-hydroxy-6-(4-methoxybenzyloxy)-

nonan-2-one (anti-41)]: A degassed solution of syn-39a (254 mg,

0.64 mmol) in THF (6.5 mL) and MeOH (3 mL) was slowly added

12–29, 90 mg, 51%) as a slightly yellow oil. Compound syn-40b at –78 °C to a freshly prepared SmBr₂suspension (0.1  in THF,

20

(major diastereomer): [α] = –10.1, [α] = –10.7, [α] = –12.4,

21 mL, 2.04 mmol, 3.2 equiv.). After 90 min at this temperature the

mixture was added into satd. aq. NaHCO₃(20 mL). After addition

of HCl (1 , 50 mL) the phases were separated and the aq. phase

589

578

546

20

[α]

= –23.5, [α]

= –45.4 (c = 2.03, CHCl₃). ¹H NMR

(400 MHz, CDCl₃/CDCl₃): δ = 0.90 and 0.98 [2ϫd, J_{3ЈЈ-Me,3ЈЈ}

436

365

=

Eur. J. Org. Chem. 2010, 4802–4822

www.eurjoc.org

4819

P. Walleser, R. Brückner

FULL PAPER

was extracted with EtOAc (3 ϫ 20 mL). The combined organic

phases were dried with MgSO₄. Removal of the solvent under re-

duced pressure and flash chromatography (2ϫ15 cm, 10 mL, cy-

clohexane/EtOAc 4:1) provided the title compound (fractions 24–

1.2 equiv.) was added and the mixture was stirred overnight at

–78 °C. After addition of satd. aq. NH₄Cl (1 mL) the phases were

separated and the aq. phase was extracted with MTBE (3ϫ1 mL).

The combined organic phases were dried with MgSO₄. Removal

38, 85 mg, 45%) as a slightly yellow oil. Compound syn-41 (major of the solvent under reduced pressure and flash chromatography

20

diastereomer): [α] = –53.7, [α] = –56.6, [α] = –66.1, [α]

(1ϫ18.5 cm, 5 mL, cyclohexane/EtOAc 10:1) provided the title

compound (fractions 18–21, 29 mg, 80%) as a slightly yellow oil.

589

578

546

436

20

1

= –114.0, [α] = –181.8; (c = 0.45, CHCl₃). H NMR (400 MHz,

CDCl₃/CDCl₃): 0.93 (dd, J_9,8–H(A)= J_9,8–H(B)= 7.3 Hz, 9-H₃), 1.31–

1.44 (m, 8-H₂), 1.48–1.65 (m, 7-H₂), AB signal (δ_A= 1.59, δ_B

365

20

Compound syn,syn-43 (major diastereomer): [α] = –10.3, [α]

589 578

20

=

= –12.0, [α]

= –14.8, [α]

= –26.1, [α] = –45.2; (c = 0.13,

365

546

436

1.70, J_AB= 14.3 Hz, A part additionally split by J_A,6= 4.1 Hz, J_A,4

= 3.6 Hz, B part additionally split by J_B,4= J_B,6= 8.8 Hz, 5-H₂),

2.15 (s, 1-H₃), AB signal (δ_A= 2.47, δ_B= 2.59, J_AB= 16.6 Hz, A

part additionally split by J_A,4= 4.5 Hz, B part additionally split by

CHCl₃). ¹H NMR (500 MHz, CDCl₃/CDCl₃): δ = 0.65 (q, J_1ЈЈ,2ЈЈ

= 7.9 Hz, 1ЈЈ-H₂), 0.87 (t, J_2ЈЈ,1ЈЈ= 7.9 Hz, 1ЈЈ-H₃), 0.92 (dd,

J_{5ЈЈ,4ЈЈ–H(A)}= J_{5ЈЈ,4ЈЈ–H(B)}= 7.3 Hz, 5ЈЈ-H₃), 1.19 (d, J_6-Me,6= 6.3 Hz,

6-CH₃), 1.32–1.48 (m, 4ЈЈ-H₂), 1.49–1.61 (m, 1ЈЈ-H₂, 3ЈЈ-H₂), AB

signal (δ_A= 1.70, δ_B= 1.88, J_AB= 13.8 Hz, A part additionally

J_B,4= 7.8 Hz, 3-H₂), 3.66 (dddd, J_6,5–H(B)= 9.0 Hz, J_6,7–H(A)

=

J_6,5–H(A)= J_6,7–H(B)= 4.4 Hz, 6-H), 3.73 (d, J_4,4–OH= 1.9 Hz, 4- split by J_A,2ЈЈ= J_A,4ЈЈЈ= 2.7 Hz, B part additionally split by J_B,2ЈЈ

OH), 3.87 (s, OCH₃), 4.20 (m_c, 4-H), AB signal (δ_A= 4.37, δ_B= J_B,4ЈЈЈ= 6.9 Hz, 5-H₂), 3.56 (m_c, 2ЈЈ-H), 3.80 (s, OCH₃), 3.93–

4.54, J_AB= 10.6 Hz, OCH₂Ar), AAЈBBЈ signal (peaks centered at 4.08 (m, 4-H, 6-H), AB signal (δ_A= 4.39, δ_B= 4.46, J_AB= 11.3 Hz,

=

δ_A= 6.86, δ_B= 7.24, 2 ϫ ortho-H, 2 ϫ meta-H). ¹³C NMR

OCH₂Ar), AAЈBBЈ signal (peaks centered at δ_A= 6.87, δ_B= 7.25,

(100 MHz, CDCl₃): δ = 14.37 (C-9), 18.13 (C-8), 30.98 (C-1), 35.76 2ϫ ortho-H, 2ϫ meta-H). ¹³C NMR (125 MHz, CDCl₃): δ = 7.95

(C-7), 40.45 (C-5), 50.70 (C-3), 55.37 (OCH₃), 67.29 (C-4), 70.29 (C-2Ј), 14.31 (C-5ЈЈ), 18.83 (C-4ЈЈ), 23.23 (CH₃-6), 36.27 (C-3ЈЈ),

(OCH₂Ar), 78.28 (C-6), 114.00 (2ϫ meta-C), 129.61 (2ϫ ortho-C), 40.74 (C-1ЈЈ), 41.62 (C-5), 55.36 (OCH₃), 67.73 (C-4), 68.73 (C-6),

130.37 (ipso-C), 159.38 (para-C), 208.83 ppm (C-2). IR (film): ν = 70.10 (OCH₂Ar), 74.64 (C-2ЈЈ), 113.81 (2ϫ meta-C), 129.64 (2ϫ

˜

3460, 3000, 2955, 2935, 2870, 1710, 1615, 1585, 1515, 1465, 1425,

ortho-C), 131.10 (ipso-C), 159.23 ppm (para-C). IR (film): ν = 2960,

˜

1360, 1300, 1250, 1175, 1035, 820, 740, 705 cm^–1.

2930, 2875, 2350, 2285, 1615, 1515, 1460, 1425, 1400, 1380, 1330,

1300, 1275, 1250, 1210, 1175, 1110, 1090, 1040, 820, 755 cm^–1

.

(4S,6S)-6-(tert-Butyldiphenylsilyloxy)-4-hydroxy-7-methyloctan-2-

one [anti-42; as a mixture (93:7) with (4R,6S)-6-(tert-butyldiphenyl-

silyloxy)-4-hydroxy-7-methyloctan-2-one (syn-42)]: This compound

was prepared from anti-40b (329 mg, 0.64 mmol) as described for

syn-41. Flash chromatography (2.5ϫ18 cm, 20 mL, cyclohexane/

HRMS (EI, 70 eV): calcd. for C₁₉H₃₁BO₄334.2315 [M]⁺; found

334.2308 (δ =2.2 ppm).

tert-Butyl{(S)-1-[(4R,6R)-2-ethyl-6-methyl-1,3,2-dioxaborinan-4-yl]-

3-methylbutan-2-yloxy}diphenylsilane [syn,anti-44; as a mixture

EtOAc 6:1) provided the title compound (fractions 11–18, 158 mg, (94:6) with tert-butyl{(S)-1-[(4S,6S)-2-ethyl-6-methyl-1,3,2-dioxa-

60 %) as a slightly yellow oil. Compound anti-42 (major dia-

borinan-4-yl]-3-methylbutan-2-yloxy}diphenylsilane (syn,syn-44)]:

This compound was prepared from anti-42 (42 mg, 0.10 mmol) as

described for syn,syn-43. Flash chromatography (1ϫ16 cm, 5 mL,

cyclohexane/EtOAc 50:1) provided the title compound (fractions

8–10, 35 mg, 77%) as a slightly yellow oil. Compound syn,anti-44

20

stereomer): [α]

= +2.5, [α]

= +2.9, [α]

= +6.8, [α]

=

589

578

546

436

20

+10.8, [α]

= +12.1 (c = 0.65, CHCl₃). ¹H NMR (400 MHz,

365

CDCl₃/CDCl₃): δ = 0.77 and 0.92 [2 ϫ d, J_7-Me,7= 6.8 Hz,

7-(CH₃)₂], 1.07 (s, 2Ј-H₉), AB signal (δ_A= 1.41, δ_B= 1.45, J_AB

=

20

14.2 Hz, A part additionally split by J_A,4= 7.1 Hz, J_A,6= 3.7 Hz,

B part additionally split by J_B,4= 8.4 Hz, J_B,6= 3.9 Hz, 5-H₂), 1.83

(qqd, J_7,8= J_7,7–Me= 6.9 Hz, J_7,6= 3.9 Hz, 7-H), 2.03 (s, 1-H₃),

AB signal (δ_A= 2.27, δ_B= 2.36, J_AB= 17.0 Hz, A part additionally

split by J_A,4= 3.5 Hz, B part additionally split by J_B,4= 8.6 Hz, 3-

H₂), 2.36 (br. d, J_{4-OH, 4}= 3.5 Hz, 4-OH), 3.82 (m_c, approximately

interpretable as ddd, J_6,5–H(A)= 7.5 Hz, J_6,5–H(B)= J_6,7= 3.8 Hz,

(major diastereomer): [α] = –20.0, [α] = –21.0, [α] = –23.4,

589 578 546

= –52.5 (c = 0.57, CHCl₃). ¹H NMR

365

20

[α]

= –36.9, [α]

436

(500 MHz, CDCl₃/CDCl₃): δ = 0.54 (q, J_{1ЈЈЈ,2ЈЈЈ}= 7.9 Hz, 1ЈЈЈ-H₂),

0.76 and 0.90 [2ϫd, J_3Ј-Me,3Ј= 6.9 Hz, 3Ј-(CH₃)₂], 0.76 (t, J_{2ЈЈЈ,1ЈЈЈ}

= 7.9 Hz, 1ЈЈЈ-H₃), 1.06 (s, 2-H₉), 1.14 (d, J_{6ЈЈ-Me,6ЈЈ}= 6.0 Hz, 6ЈЈ-

CH₃), AB signal (δ_A= 1.46, δ_B= 1.38, J_AB= 13.8 Hz, A part

additionally split by J_A,2Ј= 8.4 Hz, J_A,4ЈЈ= 3.1 Hz, J_B,2Ј= 9.6 Hz,

6-H), 4.01 (m_c, approximately interpretable as dddd, J_4,3–H(B)

=

J_B,4ЈЈ= 3.3 Hz, 1Ј-H₂), 1.56 (m_c, 5ЈЈ-H₂), 1.76 (qqd, J_3Ј,4Ј

=

J_4,5–H(B)= 8.5 Hz, J_4,5–H(A)= 7.5 Hz, J_4,3–H(A)= 3.8 Hz, 4-H), 7.35–

J_3Ј,3Ј–Me= 6.9 Hz, J_3Ј,2Ј= 3.1 Hz, 3Ј-H), 3.74–3.82 (m, 4ЈЈ-H, 6ЈЈ-

7.47 (m, 4ϫ ortho-H, 2ϫ para-H), 7.66–7.77 ppm (m, 4ϫ meta- H), 4.03 (ddd, J_{2Ј,1Ј–H(A)}= 8.2 Hz, J_2Ј,3Ј= J_{2Ј,1Ј–H(B)}= 3.2 Hz, 2Ј-

H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.27 and 18.07 [7-(CH₃)₂], H), 7.35–7.43 (m, 4ϫ ortho-H, 2ϫ para-H), 7.67–7.71 ppm (m, 4ϫ

19.68 (C-1), 27.20 (C₃-2Ј), 30.54 (C-1Ј), 33.51 (C-7), 39.00 (C-5), meta-H). ¹³C NMR (125 MHz, CDCl₃): δ = 7.08 (C-2ЈЈЈ), 16.92

50.70 (C-3), 64.51 (C-4), 74.91 (C-5), 127.61 and 127.63 (4ϫ meta- and 17.77 [(CH₃)_2–3Ј], 19.75 (CH₃-6ЈЈ), 23.23 (C-1), 27.25 (C₃-2),

C), 129.69 and 129.72 (4ϫ ortho-C), 134.30 and 134.47 (2ϫ para-

33.52 (C-3Ј), 40.20 (C-1Ј), 41.21 (C-5ЈЈ), 67.71 (C-4ЈЈ), 67.97 (C-

6ЈЈ), 74.21 (C-2Ј), 127.40 and 127.46 (4 ϫ meta-C), 129.46 and

129.54 (4ϫ ortho-C), 134.62 and 134.99 (2ϫ para-C), 136.05 and

C), 136.14 and 136.15 (2ϫ ipso-C), 208.96 ppm (C-2). IR (film): ν

˜

= 3435, 3050, 3070, 2960, 2930, 2895, 2860, 1715, 1470, 1430, 1390,

1360, 1310, 1250, 1160, 1110, 1075, 1050, 1005, 940, 940, 880, 820,

740, 705, 690, 610 cm^–1. C₂₅H₃₆O₃Si (412.64): calcd. C 72.77, H

7.79; found C 72.65, H 7.92.

136.13 ppm (2ϫ ipso-C). IR (film): ν = 3070, 2960, 2930, 2860,

˜

2355, 1640, 1460, 1430, 1400, 1330, 1300, 1275, 1215, 1150, 1110,

1080, 1050, 905, 820, 790, 735, 700, 685, 615 cm^–1. C₂₇H₄₁BO₃Si

(452.51): calcd. C 71.76, H 9.42; found C 71.67, H 9.13.

(4S,6S)-2-Ethyl-4-[(R)-2-(4-methoxybenzyloxy)pentyl]-6-methyl-

1,3,2-dioxaborinane {syn,syn-43; as a mixture (92:8) with (4R,6R)-

2-ethyl-4-[(R)-2-(4-methoxybenzyloxy)pentyl]-6-methyl-1,3,2-dioxa-

borinane (syn,anti-43)}: BEt₃(1.0  in THF, 0.13 mL, 0.13 mmol,

1.2 equiv.) was dissolved in a 4:1 mixture of THF (0.6 mL) and

MeOH (0.15 mL) and stirred at room temp. for 1 h. The mixture

was then cooled to –78 °C and a solution of syn-41 (32 mg,

0.11 mmol) in THF (0.5 mL) was added. After the system had been

kept for 2 h at this temperature NaBH₄(5.0 mg, 0.13 mmol,

Preparation of SmI₂in THF: 1,2-Diiodoethane (1.0 g) was dis-

solved in MTBE (30 mL), washed with satd. aq. Na₂SO₃

(2ϫ30 mL), and dried with MgSO₄. After evaporation of the sol-

vent the obtained residue (500 mg, 1.77 mmol) was dissolved in

THF (17 mL) and degassed at –78 °C. The resulting solution was

cannulated onto Sm powder (40 mesh, 279 mg, 1.86 mmol,

1.05 equiv.). After stirring at room temp. for 16 h, we obtained a

dark blue solution. Its concentration in SmI₂was assumed to be

4820

www.eurjoc.org

Eur. J. Org. Chem. 2010, 4802–4822

1,3,5-Triols by Asymmetric Dihydroxylation and Deoxygenation

0.1 . Because of its low stability this solution was made directly

before it was used.

615 cm^–1. HRMS (EI, 70 eV): calcd. for C₂₅H₃₅O₄Si 427.2305 [M –

C₄H₉]⁺; found 427.2301 (δ = 0.9 ppm).

(2R,4S,6R)-2-Hydroxy-6-(4-methoxybenzyloxy)nonan-4-yl Isobut-

yrate [anti,syn-45; as a mixture (89:11) with (2R,4S,6R)-2-hydroxy-

6-(4-methoxybenzyloxy)nonan-4-yl isobutyrate (anti,anti-45)]: A

freshly prepared SmI₂suspension (0.1  in THF, 0.15 mL, 15 mol-

%) was slowly added at –10 °C to a degassed solution of syn-41

(30 mg, 0.10 mmol) and isobutyraldehyde (0.06 mL, 44.1 mg,

0.61 mmol, 6.0 equiv.) in THF (1 mL). After the system had been

kept for 60 min at this temperature, satd. aq. NaHCO₃(1 mL) was

added, and the phases were separated. The aq. phase was extracted

with EtOAc (3 ϫ 1 mL) and the combined organic phases were

dried with MgSO₄. Removal of the solvent under reduced pressure

and flash chromatography (1ϫ15 cm, 5 mL, cyclohexane/EtOAc

4:1) provided the title compound (fractions 10–12, 22 mg, 59%) as

a slightly yellow oil. Compound anti,syn-45 (major diastereomer):

Acknowledgments

We than the European Graduate College “Catalysts and Catalytic

Reactions for Organic Synthesis” of the Deutsche Forschungsge-

meinschaft (DFG) for support of this project.

[1] a) J.-M. Beau, in: G. Lukacs, M. Ohno (Ed.) Recent Progress

in the Chemical Syntheses of Antibiotics, Springer Verlag,

Berlin, 1990, 137–179; b) S. Omura, H. Tanaka, S. Omura

(Eds.), Macrolide Antibiotics, Academic Press Inc., New York,

1994, pp. 351–404; c) S. D. Rychnovsky, Chem. Rev. 1995, 95,

2021–2040; d) C. J. Sinz, S. D. Rychnovsky, Top. Curr. Chem.

2001, 216, 52–92.

[2] a) T. Oishi, T. Nakata, Synthesis 1990, 635–645; b) C. Schnei-

der, Angew. Chem. 1998, 110, 1445–1448; c) C. Schneider, An-

gew. Chem. Int. Ed. 1998, 37, 1375–1378; d) J. Dougherty, M.

Zhou, G. A. O’Doherty, Chemtracts: Org. Chem. 2005, 18,

349–363; e) S. E. Bode, M. Wolberg, M. Müller, Synthesis 2006,

4, 557–588.

20

[α] = –9.7, [α] = –11.0, [α] = –12.5, [α] = –21.9, [α] =

589

578

546

436

365

1

–33.6 (c = 0.43, CHCl₃). H NMR (400 MHz, CDCl₃/CDCl₃): δ =

0.89 (dd, J_{9Ј,8Ј–H(A)}= J_{9Ј,8Ј–H(B)}= 7.3 Hz, 9Ј-H₃), 1.14 und 1.16

[2ϫd, J_2-Me,2= 6.9 Hz, 3-(CH₃)₂], 1.16 (d, J_1Ј,2Ј= 6.2 Hz, 1Ј-H₃),

1.28–1.54 (m, 7Ј-H₂, 8Ј-H₂), 1.55–1.62 (m, 5Ј-H₂), AB signal (δ_A

1.66, δ_B= 1.98, J_AB= 14.2 Hz, A part additionally split by J_A,2Ј

=

[3] K. Körber, Dissertation, University of Freiburg, 2004.

[4] P. Risch, Rapport de Stage, University of Freiburg, 2005.

[5] K. Körber, P. Risch, R. Brückner, Synlett 2005, 19, 2905–2910.

[6] A. Zörb, R. Brückner, Eur. J. Org. Chem. 2010, 000–000, pre-

ceding contribution in this issue.

6.6 Hz, J_A,4Ј= 4.9 Hz, B part additionally split by J_B,2Ј= 8.0 Hz,

J_B,4Ј= 6.1 Hz, 3Ј-H₂), 2.53 (qq, J_2,3= J_2,2–Me= 7.0 Hz, 2-H), 3.10

(d, J_2Ј-OH,2Ј= 3.8 Hz, 2Ј-OH), 3.41 (dddd, J_{6Ј,5Ј–H(A)}= 6.2,

J_{6Ј,5Ј–H(B)}= J_{6Ј,7Ј–H(A)}= 6.1 Hz, J_{6Ј,7Ј–H(B)}= 5.8 Hz), 3.62 (m_c, 4Ј-

H), 3.80 (s, OCH₃), 4.42 (s, OCH₂Ar), 5.18 ppm (m_c, 2Ј-H),

AAЈBBЈ signal (peaks centered at δ_A= 6.87, δ_B= 7.26, 2ϫ ortho-

H, 2ϫ meta-H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.23 (C-9Ј),

18.41 (C-8Ј), 19.11 and 19.20 [(CH₃)_2–3], 22.95 (C-1Ј), 34.34 (C-2),

36.00 (C-7Ј), 39.25 (C-3Ј), 45.02 (C-5Ј), 55.39 (OCH₃), 63.29 (C-

4Ј), 69.16 (C-2Ј), 70.43 (OCH₂Ar), 75.18 (C-6Ј), 113.89 (2ϫ meta-

C), 129.51 (2 ϫ ortho-C), 130.79 (ipso-C), 159.23 (para-C),

[7] a) D. Xu, G. A. Crispino, K. B. Sharpless, J. Am. Chem. Soc.

1992, 114, 7570–7571; b) H. Becker, M. A. Soler, K. B.

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X. She, X. Pan, J. Org. Chem. 2009, 74, 3930–3932; m) See

178.35 ppm (C-1). IR (film): ν = 3425, 2960, 2930, 2875, 2285,

˜

1730, 1615, 1515, 1465, 1385, 1300, 1250, 1200, 1160, 1070, 1035,

820, 755 cm^–1. HRMS (CI, NH₃): calcd. for C₂₁H₃₅O₅367.2485 [M

+ H]⁺; found 367.2478 (+1.8 ppm).

(2S,4R,6S)-6-(tert-Butyldiphenylsilyloxy)-2-hydroxy-7-methyloctan-

4-yl Isobutyrate [anti,anti-46; as a mixture (89:11) with (2R,4S,6S)-

6-(tert-butyldiphenylsilyloxy)-2-hydroxy-7-methyloctan-4-yl isobu-

tyrate (anti,syn-46)]: This compound was prepared from anti-42

(32 mg, 0.08 mmol) as described for anti,syn-45. Flash chromatog-

raphy (1ϫ14 cm, 5 mL, cyclohexane/EtOAc 6:1) provided the title

compound (fractions 13–15, 23 mg, 61%) as a slightly yellow oil.

ref.^[26a–26j]

.

[8] S.-K. Kang, S.-G. Kim, D.-C. Park, J.-S. Lee, W.-J. Yoo, C. S.

Pak, J. Chem. Soc. Perkin Trans. 1 1993, 9–10.

20

Compound anti,anti-46 (major diastereomer): [α] = +4.6, [α]

[9] C. H. Hövelmann, K. Muñiz, Chem. Eur. J. 2005, 11, 3951–

589

578

20

3958.

= +5.4, [α]

= +6.5, [α]

= +10.5, [α] = +13.5 (c = 0.23,

546

436

365

CHCl₃). ¹H NMR (400 MHz, CDCl₃/CDCl₃): δ = 0.72 and 0.91

[2ϫd, J_7Ј-Me,7Ј= 6.8 Hz, 7Ј-(CH₃)₂], 0.98 and 0.99 [2ϫd, J_7Ј-Me,7Ј

= 6.9 Hz, 7Ј-(CH₃)₂], 1.05 (s, 2ЈЈ-H₉), 1.10 (br. d, J_1Ј,2Ј= 5.8 Hz,

1Ј-H₃), 1.34–1.46 (m, 5Ј-H₂), AB signal (δ_A= 1.55, δ_B= 1.69, J_AB

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1724.

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M. J. Shapiro, Tetrahedron Lett. 1987, 28, 155–158; d) K.-M.

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pic, M. J. Shapiro, Chem. Lett. 1987, 1923–1926.

= 14.5 Hz, A part additionally split by J_A,2Ј= 7.8 Hz, J_A,4Ј

=

3.2 Hz, J_B,2Ј= 9.2 Hz, J_B,4Ј= 3.5 Hz, 3Ј-H₂), 1.65–1.78 (m, 7Ј-H),

2.33 (qq, J_2,1= J_2,2–Me= 7.0 Hz, 2-H), 3.12 (d, J_2Ј-OH,2Ј= 2.9 Hz,

2Ј-OH), 3.42–3.50 (m, 4Ј-H, 6Ј-H), 5.02 (m_c, 2Ј-H), 7.32–7.46 (m, [12] For Narasaka–Prasad reductions of δ-chiral β-hydroxy

4 ϫ ortho-H, 2ϫ para-H), 7.62–7.73 ppm (m, 4 ϫ meta-H). ¹³C

NMR (100 MHz, CDCl₃): δ = 16.87 and 17.60 [(CH₃)_2–7Ј], 18.82

and 19.06 [(CH₃)_2–2], 19.52 (C-1Ј), 22.69 (C-1ЈЈ), 27.21 (C₃-2ЈЈ),

33.22 (C-2), 34.16 (C-7Ј), 38.20 (C-5Ј), 45.71 (C-3Ј), 63.08 (C-4Ј),

69.29 (C-2Ј), 74.87 (C-6Ј), 127.46 and 127.63 (4ϫ meta-C), 129.61

and 129.64 (4ϫ ortho-C), 133.92 and 134.62 (2ϫ para-C), 136.05

ketones, see: a) Y. Mori, Y. Kohchi, T. Ota, M. Suzuki, Tetrahe-

dron Lett. 1990, 31, 2915–2916; b) Y. Mori, Y. Kohchi, M. Su-

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and 136.15 (2ϫ ipso-C), 178.09 ppm (C-1). IR (film): ν = 3070,

˜

2960, 2930, 2860, 2355, 1640, 1460, 1430, 1400, 1330, 1300, 1275,

1215, 1150, 1110, 1080, 1050, 905, 820, 790, 735, 700, 685,

Eur. J. Org. Chem. 2010, 4802–4822

www.eurjoc.org

4821

P. Walleser, R. Brückner

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[31] The usual workup of Narasaka–Prasad reductions entails dis-

solving the crude product in MeOH, evaporating the resulting

solution to dryness, and repeating this procedure several times.

We failed to expel the boron in this manner because we skipped

the treatment with MeOH for fear of a concomitant evapora-

tive loss of the desired compound.

Received: March 1, 2010

Published Online: July 19, 2010

4822

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Article Doi

Stereocontrolled synthesis of 1,3,5-triols by an iteration of asymmetric dihydroxylation and deoxygenation

DOI: 10.1002/ejoc.201000280

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