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a-Silyl Ketone Controlled Asymmetric Syntheses Dieter Enders,* Johannes Adam, Daniela Klein, Thomas Otten Institut für Organische Chemie, Rheinisch-Westfälische Technische Hochschule, Professor-Pirlet-Straße 1, 52074 Aachen, Germany Fax +49(0)241/8888-127; E-mail: [email protected] Received 17 September 1999

Abstract: Enantiomerically pure a-silyl substituted ketones can be easily prepared via the SAMP/RAMP hydrazone method starting from simple and cheap ketones and silylating reagents. These compounds are very useful precursors for the regio- and stereoselective formation of carbon-carbon and carbon-heteroatom bonds with very high asymmetric inductions in many cases. A great variety of important organic reactions using a-silyl ketones as well as a-silyl aldehydes and their application for the synthesis of bioactive compounds are presented. 1 2 2.1 2.2 3 3.1 3.1.1 3.1.2 3.1.3 3.1.4 3.1.5 3.2 4 5 5.1 5.2 6

Introduction Synthesis of a-Silyl Ketones and a-Silyl Aldehydes General Concepts for the Synthesis of a-Silyl Ketones and a-Silyl Aldehydes a-Silyl Ketones and a-Silyl Aldehydes via the SAMP/RAMP Hydrazone Method a-Silyl Carbonyl Compounds in Stereoselective Bond Formation Stereoselective Carbon-Carbon Bond Formation Aldol Reactions Michael Additions Mannich Reactions Darzens Reactions a4-Umpolung Reactions Stereoselective Carbon-Hetero Atom Bond Formation Miscellaneous Application of a-Silyl Controlled Asymmetric Syntheses Pheromone Synthesis Synthesis of Mevinolin Analogues Conclusion

method where an asymmetric 1,5-induction takes place we decided to introduce the directing group in the a´-position of the carbonyl group to achieve a 1,3-induction. The requirements for this group are that it should be readily available, easily introduced with high enantioselectivity as well as being smoothly removed without racemisation. These requirements are best fulfilled by the silyl group. Additionally, due to the steric demand of the various bulky trialkylsilyl groups high diastereofacial differentiation can be expected. For the final removal of the silicon group there are in general two methods proven to be suitable. The nucleophilic attack at silicon especially by fluoride anion and the removal under acidic conditions are known to work very well. In this review we will discuss the enantioselective synthesis of a-silyl ketones and aldehydes and their use in the regio- and stereocontrolled formation of new carbon-carbon and carbon-heteroatom bonds. The new concept of asymmetric electrophilic substitutions a to the carbonyl group employing R3Si as a “traceless” directing group is exemplified in the sequence A Æ B Æ C.

R2

A

Key words: asymmetric synthesis, hydrazones, organosilicon compounds, Michael additions, aldol reactions

1

Introduction

Reactions of carbonyl compounds belong to the most important and most investigated disciplines in organic chemistry. This is mainly due to their availibility and the great variety of transformations and reactions carbonyl compounds can undergo. Furthermore, the development of asymmetric synthesis has increased immensely during the last few decades. In this context of carbonyl chemistry and asymmetric synthesis, one of the pioneering and most successful methodologies developed is the SAMP/RAMP hydrazone method.1 This has allowed access to a wide range of enantiomerically and diastereomerically pure carbonyl compounds and their derivatives. Nevertheless, it was desired to develop further methodologies for stereocontrolled synthesis of a- and a,b-substituted carbonyl compounds. In contrast to the SAMP/RAMP hydrazone

hydrazone method

O R1

O

EX

R1

O R1

E R2

R2

R3Si

B

C

ee > 98 %

high ee's

2

Synthesis of a-Silyl Ketones and a-Silyl Aldehydes

2.1

General Concepts for the Synthesis of a-Silyl Ketones and a-Silyl Aldehydes

Research into the synthesis and use of a-silyl carbonyl compounds in organic chemistry started in the early fifties.2 As depicted in Scheme 1, the general retrosynthetic analysis for the synthesis of a-silyl ketones and aldehydes offers many different pathways. Hauser and Hance were the first to report the synthesis of a-silyl ketones by condensation of acetic anhydride with a-silylated Grignard reagents.3 This work was continued by Demuth4 as well as Seitz and Zapata.5 They found that trimethylsilylmethyllithium adds smoothly to methyl and ethyl esters as well as to carboxylic acid chlorides furnish-

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ing a-trimethylsilyl ketones in high yields (route a). Alternatively, a-silyl ketones have been sythesized by reaction of a-silyl esters with an excess of Grignard reagent (route c).6 A third approach has been via the oxidation of vinylsilanes (route d). For example, epoxidation of vinylsilanes followed by Lewis-acid mediated rearrangement has been reported.7 This is one of very few methods which has been performed enantioselectively. Sharpless epoxidation of (E)-3-(tert-butyldimethylsilyl)-2-methyl-2-propen-1-

ol [(E)-1] furnished in 78% yield the enantiomerically pure epoxysilane 2 (ee ≥ 98%). After Swern oxidation and Wittig olefination Gilloir and Malacria obtained the corresponding silyl substituted vinyloxirane 3 in 54% yield. Finally the palladium(0) catalysed 1,2-migration of the silyl group led to the desired b,g-unsaturated a-silyl ketone 4 in 87% yield. Unfortunately only a moderate enantiomeric excess of ee = 77% was achieved (Scheme 2). Furthermore the absolute configuration of 4 has not been

Biographical Sketches

Synlett 2000, No. 10, 1371–1384

Dieter Enders was born in 1946 in Butzbach, Germany. He studied chemistry at the Justus Liebig Universität Gießen and received his Dr. rer. nat. in 1974 under the supervision of Prof. D. Seebach. After postdoctoral studies at Harvard University with Prof. E. J.

Corey he went back to Gießen and obtained his habilitation in 1979. In 1980 he moved to the University of Bonn as an associate professor and in 1985 to his present position as Professor of Organic Chemistry at the Rheinisch-Westfälische Technische Hochschule

Aachen. His current research interests are asymmetric synthesis, new synthetic methods using organometallics and the stereoselective synthesis of biologically active compounds.

Johannes Adam was born in 1970 in Mönchengladbach, Germany. He studied chemistry at the RWTH

Aachen and received his Dr. rer. nat. in 1999 under the supervision of Prof. D. Enders. He is currently a post-

doctoral fellow at Universite Claude Bernard Lyon 1 in the laboratories of Prof. O. Piva.

Daniela Klein was born in 1971 in Leverkusen, Germany. She studied chemistry at the University of Würzburg, ETH Zürich,

University of Freiburg and RWTH Aachen and received her Dr. rer. nat. in 1999 under the supervision of Prof. D. Enders. She cur-

rently works on fine chemicals’ research in the main laboratory of BASF in Ludwigshafen, Germany.

Thomas Otten was born in 1970 in Würselen, Germany. He studied chemistry at the RWTH Aachen and re-

ceived his Dr. rer. nat. under the supervision of Prof. D. Enders in 2000. He currently works for the pharmaceu-

tical company Grünenthal GmbH, Aachen

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R1

X

+ SiR3 a

OSiR3 R1

e

R2

mation of a new silicon-oxygen bond, to give silyl enol ethers. Therefore, a protection of the carbonyl group can not be avoided. As shown by Corey, Enders et al.14 as well as by Hudrlik and Kulkarni15 this protection can be achieved via the formation of the corresponding imines and N,N-dialkylhydrazones (route b). Deprotection has been carried out by either acid hydrolysis or ozonolysis. Advantages of the hydrazone method are cheap available starting materials, high yields over three to four steps as well as its general applicability. Furthermore, this approach has been adapted by Enders to asymmetric synthesis by using SAMP/RAMP as chiral auxiliary.16 This methodology will be described in the following section.

R2

O

d c

Z b

O a

R1

+ XSiR3

b

d

R2

R1

R2

Z = NR, NNR2

SiR3 c O R2

R1

X

SiR3

R2 + R1 SiR3

a-Silyl Ketones and a-Silyl Aldehydes via the SAMP/RAMP Hydrazone Method

2.2

X = leaving group; e.g.: Cl, Br, I, OR etc.

Scheme 1

determined so far.8 Overall, this epoxidation and rearrangement strategy allows access to enantiomerically enriched, tertiary and quarternary a-silyl aldehydes.

O tBuMe2Si

OH

78 %

tBuMe2Si

37 %

CH3

(E)-1

O

* H2C tBuMe2Si CH3 4 ee = 77 %

Sharpless epoxidation

CH3

O

87 %

Pd(0)

1. Swern oxidation 2. Wittig olefination

The general concept sets up with formation of the SAMP/ RAMP hydrazones. After silylation and (where required) alkylation under kinetic control, the auxiliary may be removed by ozonolysis with regeneration of the carbonyl group and without racemisation. In order to synthesize a wide range of substances with complete stereo- and regiocontrol we have developed two methods (method A and B) complementing each other. In method A, aldehydes, symmetrically substituted ketones and ketones which contain acidic protons in one of the a-positions are used, meaning that the formation of mixtures of regioisomers is not possible. O R3Si

R2 tBuMe2Si

O

CH3

R1

OH ee ≥ 98 %

R2 R1

(R)-8

5

ee ≥ 96 %

54 % 2

1373

a-Silyl Ketone Controlled Asymmetric Syntheses

3

CH2

OCH3 N

Scheme 2

NH2

According to route c (Scheme 1) dihydroxylation, instead of epoxidation, leads after a Lewis-acid mediated 1,2-silicon shift to a-silyl ketones and aldehydes.9 In a “contrathermodynamic” approach devised by Corey and Rücker, silyl enol ethers possessing sterically hindered silyl groups undergo rearrangement to the corresponding asilyl ketones.10 By bromine/lithium exchange of 1-bromo2-trimethylsilyloxyethylenes and subsequent 1,3-silyl migration Duhamel et al. succeeded in isolating a-trimethylsilyl aldehydes.11 Another access to a-silyl aldehydes has been developed by hydroformylation of vinylsilanes. Unfortunately this reaction does not proceed smoothly and mixtures of a- and b-silylated aldehydes are obtained.12 In contrast to carboxylic acid esters, the direct a-silylation of ketones and aldehydes in a deprotonation-silylation sequence is not possible, with only one known exception.13 Owing to its oxophilicity such attempts result in the for-

SAMP

OCH3 N

N 2

R R1

1. Et2O, LDA (0 °C) or t-BuLi (−78 °C) 2. R3SiOSO2CF3, −78 °C → rt

O3, −78 °C, pentane

OCH3 N R3Si (S,R)-7

(S)-6

N R2

R1 de ≥ 96 %

Scheme 3

Both methods start with condensation of SAMP and carbonyl compounds 5 to afford the desired SAMP hydrazones (S)-6. Reaction conditions differ according to the carbonyl compounds used. Aldehydes react in dichloromethane or diethyl ether at 0 - 25 °C. Dialkyl ketones are available by reaction without solvent at 60 °C, whereas arylalkyl ketones need to be converted under conditions where water is removed such as in the presence of 4 Å mo-

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lecular sieves or using a Dean-Stark trap. After workup and distillation under reduced pressure the SAMP hydrazones (S)-6 are formed in most cases in more than 90% yield. Use of the enantiomer RAMP instead of SAMP works in the same way to give hydrazones (R)-6.17 In method A hydrazones (S)-6 are converted to the lithiated azaenolates by treatment with lithium diisopropylamide (LDA) for four hours at 0 °C or by metallation with tert-butyllithium (t-BuLi) for two hours at -78 °C. After addition of the appropriate silyl triflate at -78 °C the reaction mixture is slowly warmed up to room temperature. Workup and purification either by distillation or by column chromatography affords the a-silyl hydrazones (S,R)-7 in high yields, excellent diastereoselectivities of de ≥ 96%, and in varying E/Z ratios (Scheme 3). The cheaper and easier to handle silyl chlorides were found to be unreactive for this transformation, therefore requiring the use of the triflates. The solvent of choice is anhydrous diethyl ether. Tetrahydrofuran is not suitable because the Lewis-acid promoted ring opening with subsequent stereoselective siloxybutylation of the azaenolate to form (S,R)-9 is far faster than the desired silylation (Scheme 4).18

OCH3 N

N R2

OCH3 1. LDA, THF, 0 °C 2. R3SiOSO2CF3, −78 °C → rt

N R3SiO

1

(S)-6

R

H3CO H3C CH3 N Si H3C H3C CH3 CH3 (S,R)-7a

Figure 1

during reduction. In order to find the best conditions for ee-determination, racemic samples are necessary. They are easily accessible via the synthetic route depicted in Scheme 4 using N,N-dimethylhydrazine instead of SAMP.20 The use of this method for the preparation of a-silyl dialkyl ketones proved problematic due to poor regioselectivity of the a-silylation of the corresponding dialkyl ketone hydrazones. Furthermore, this methodology is limited by the accessibility and ease of preparation of the corresponding silyl triflates. Consequently, it was necessary to develop an alternative route (method B) involving a-silylation of methyl ketone and aldehyde hydrazones with commercially available or readily accessible chlorosilanes, followed by stereoselective a-alkylation with the corresponding alkyl halides (Scheme 5).

N R2

4

OCH3

1

(S,R)-9

N

R

N

de ≥ 96 %

N

O R3Si

R2

H3C

Scheme 4

(S)-8

(S)-6

R2 R

1

ee ≥ 96 %

If unsymmetrically substituted hydrazones (R2 π CH2R1) are used they should not contain acidic protons both in aand a´-position to avoid formation of regioisomeric compounds in unfavorable ratios. The given absolute and relative configuration is based on mechanistic considerations related to the extensively studied SAMP/RAMP hydrazone method, spectroscopic data and X-ray structure analysis of compound (S,R)-7a (R1 = CH3, R2 = Ph; Figure 1).19 Finally, ozonolysis of the a-silylated hydrazone (S,R)-7 allows access to the virtually enantiomerically pure a-silyl ketones and aldehydes (R)-8 (ee ≥ 96%). Yields range typically from 85-96%. The determination of enantiomeric excesses is easily done by 1H NMR shift experiments using Eu(hfc)3 or Eu(tfc)3 as reagents. A more accurate procedure is to carry out gas chromatography using a chiral stationary phase with the corresponding b-silyl alcohols. These b-silyl alcohols are obtained by reduction of the carbonyl function using LiAlH4. Unfortunately, application of this procedure is not suitable for all a-silyl ketones and aldehydes. For instance the five-, six- and seven-membered cyclic ketones undergo racemisation Synlett 2000, No. 10, 1371–1384

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1. LDA, THF or Et2O, 0 °C 2. R3SiCl, −78 °C → rt

OCH3 N

N

R3Si

R2 (S)-10

O3, −78 °C, pentane

OCH3

1. LDA, THF or Et2O, 0 °C 2. R1X, −78 °C → rt

N R3Si (S,S)-7

X = leaving group e.g.: Cl, Br, I

N R2

R1 de ≥ 96 %

Scheme 5

Again, the hydrazones (S)-6 are accessible according to standard methods from acetaldehyde or methyl ketones. Deprotonation with LDA can be carried out either in diethyl ether or in THF. The resultant azaenolates were converted in high yields (70 – >99%) to the a-silylated hydrazones (S)-10 by treatment with trisubstituted chlorosilanes. Owing to the complete regioselectivity of the deprotonation at the methyl group, the regioisomeric

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a´-silylated hydrazones never have been observed. In the next step deprotonation using LDA followed by alkylation with alkyl halides was carried out. Since the silicon stabilizes the negative charge in the a-position, only the desired regioisomer (S,S)-7 was observed. Yields are usually high and diastereofacial differentiation is complete to deliver enantiomerically and diastereomerically pure a-silyl hydrazones (S,S)-7. As described before, racemisation free removal of the auxiliary by ozonolysis furnishes the virtually enantiomerically pure a-silyl ketones and aldehydes (S)-8.

Formally, the order of alkylation and silylation in the first (Scheme 3) and second method (Scheme 5) is reversed. This results in the possibility to separately prepare both enantiomeric a-silyl carbonyl compounds using a single auxiliary, namely SAMP. In case of a-silylated aldehyde hydrazones (S,S)-7 (R2 = H) a further deprotonation and alkylation sequence can be carried out to furnish quarternary substituted a-silyl hydrazones 11 (Scheme 6).21 For this deprotonation the very strong and sterically less hindered base methyllithium is necessary. The desired a-silyl hydrazones 11 are obtained in moderate to good yields (43 - 87%). The moderate yields in case of EX = MeOCOCl are explained by the occurrence of N-acylation as a side reaction. The configuration of the quarternary stereogenic center has been determined by X-ray structure analysis of compound (S,R)-11a (R1 = CH3, E = C2H5). The final cleavage of the CN-double bound furnishes a-silyl aldehydes and carboxylic acids 12 with a quarternary stereogenic center in high enantiomeric excesses (ee = 85 - 98%).

OCH3 N

1375

a-Silyl Ketone Controlled Asymmetric Syntheses

3

a-Silyl Carbonyl Compounds in Stereoselective Bond Formation

3.1

Stereoselective Carbon-Carbon Bond Formation

3.1.1

Aldol Reactions

The aldol reaction is one of the most important tools for the carbon-carbon bond formation in organic chemistry. In particulary asymmetric versions are of great synthetic interest for the preparation of biologically active compounds. Enantiomerically pure a-silyl ketones can be used as efficient chiral methylene components in asymmetric aldol reactions with very high inductions.22 As is depicted in Scheme 7, the a-silyl ketone (R)-13 was initially converted to the boron enolate (R)-14 with di-n-butyl boryl triflate in the presence of diisopropylethyl- amine. Subsequent addition to aldehydes at - 78 °C led, after oxidative workup and flash column chromatography, to the synconfigured aldol products 15 with excellent diastereo- and enantiomeric excesses (desyn = 92 - ≥ 98%, ee ≥ 98%). Epimerisation and racemisation free desilylation with aqueous tetrafluoroboronic acid (60%) in THF furnished the syn-products 16 in good overall yields (55-68%) and very high diastereomeric and enantiomeric purity (de = 92 - ≥ 98%, ee ≥ 98%). The diastereomeric and enantiomeric excesses were determined by 13C- and 19 F NMR-spectroscopy of the corresponding (S)-MTPA esters.

O

N

t-BuMe2Si

tually complete enantiomeric excesses and with very high regiocontrol. In the next chapter their application to stereo- and regiocontrolled asymmetric synthesis will be discussed.

H

t-BuMe2Si 31 - 49 %

(S)-10

H(OH)

ee = 85 - 98 %

H3C

H3C

CH3

t-BuMe2Si 1. LDA, Et2O, −50 °C 2. R1I, −100 °C

79 - 97 %

O3, −78 °C, pentane

R CH3

55 - 68 %

(R)-13

66 - 82 %

OH

O

O

E R1

12

syn-16 de = 92- > 98 %, ee > 98 %

OCH3 N t-BuMe2Si

N H

R1

OCH3 1. MeLi, THF, −100 °C 2. EX, −100 °C t-BuMe2Si 43 - 87 %

(S,S)-7

de = 88 - 93 %

11 EX = MeOCOCl, EtI

N

N

n-Bu2BOSO2CF3

HBF4,/H2O, THF

i-Pr2NEt, CH2Cl2

- 20 °C, 1-2 d

- 10 °C, 2h H

E R1 de = 85 - 98 %

OBBu2 H3C

CH3

1. RCHO, - 78 °C 2. [O] 3. Chromatography

t-BuMe2Si

Scheme 6

t-BuMe2Si

(R)-14

In conclusion, we have developed efficient methods for preparing a wide range of a-silyl carbonyl compounds in good overall yields over three to five steps, in high to vir-

OH

O H3C

R CH3 15

de = 92- > 98 %, ee > 98 %

Scheme 7

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Table 1

Table 2

[a] (S)-13 was used

The correlation between the Z/E ratio of the boron enolate and the syn/anti ratio of crude compounds 16 (9/1 in each case) allows the assumption of a practically complete asymmetric induction. Boron mediated asymmetric aldol reactions may also be carried out using 4-silyl substituted 2,2-dimethyl-1,3-dioxan-5-one (S)-17 as the chiral methylene component, resulting in the formation of the anti-configured aldol products (S,S,S)-19.23 As is depicted in Scheme 8, the cyclic silyl ketone was transformed to the corresponding boron enolate (S,E)-18 (c-Hex2BCl, N,N-dimethylethylamine) having the only possible (E)-configuration. Aldol reaction with aldehydes and following oxidative workup (H2O2, pH-7-buffer/MeOH) afforded the virtually diastereo- and enantiomerically pure (de, ee = 96 - ≥ 98%) anticonfigured products 19 in very good yields (78-93%).

inferred from NMR-NOE-experiments, since the absolute configuration of the starting ketone 17 was well known. Epimerisation free cleavage of the carbon-silicon bond was carried out using the triethylamine-trihydrofluoride complex (TREAT-HF) 24 as a mild cleavage reagent. Other methods tested proved to be unsuitable, because of considerable epimerisation (TBAF, THF, 1h, - 78 °C; TBAF, NH4F) or removal of the isopropylidene group under acidic conditions (HBF4, Et2O; HBF4,THF/H2O; HF, MeCN). The cleavage products (S,S)-20 were obtained in good yields (64-79%) and with very high diastereo- and enantioselectivity (de, ee > 96%). The (S,S)-configuration of the desilylated derivatives could be proved by X-ray structure analysis of crystalline 20c. 3.1.2

OH

O

O t-HexMe2Si

R O

O

O 50 - 73 %

O

H3C CH3

H3C CH3

(S,S)-20 ee > 96 %

(S)-17

de, ee = 96 - > 98 %

c-Hex2BCl, EtMe2N 67 - 79 %

Et2O

THF

c-Hex2BO RCHO, Et2O O

OH

O

t-HexMe2Si O

3HF,

Et3N

t-HexMe2Si

R O

78 - 93 %

H3C CH3

O

H3C CH3 (S,S,S)-19

(S,E)-18

de, ee = 96 - > 98 %

Scheme 8

The diastereomeric excesses of the hydroxy ketones and the corresponding Mosher esters were determined by 1Hand 13C NMR-spectroscopy. The determination of the absolute (S,S,S)-configuration of compounds 19 was Synlett 2000, No. 10, 1371–1384

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Michael Additions

In continuation of our investigations to extend the utility of a-silyl controlled asymmetric reactions, a-silyl ketones were employed as nucleophilic components in asymmetric Michael additions. Thus, new methods for the highly stereoselective 1,4-addition to a,b-unsaturated derivatives, such as enones25 or nitroalkenes,26 have been developed. As shown in Scheme 9, the a-silyl ketone (R)-21 was first transformed regioselectively to the corresponding (Z)-silyl enol ether 22 (Z:E = 99:1) using Kuwajima’s method. After subsequent 1,4-addition to acyclic enones in the presence of catalytic amounts of trityl perchlorate the 1,5diketones 23 were obtained in good yields (81-82%) and high diastereoselectivities of the anti-diastereomer (anti : syn = 98:2 - 88:12). Desilylation with aqueous tetrafluoroboric acid induced an intramolecular aldol condensation resulting in the formation of the cyclic enones 24 in good yields (63-65%), moderate to good diastereomeric excesses but excellent enantiomeric excesses (ee > 95%), which were proved by shift-experiments using Eu(hfc)3. The ratios of diastereomers were determined by NMR-spectroscopy. The configuration given is based on mechanistic considerations assuming that the enone approaches the silyl enol ether from the opposite face of the bulky silyl group in a chair like transition state. In addition, reaction of the silyl enol ether 22 with cyclic enones led to the corresponding Michael adducts 25, how-

© Thieme Stuttgart · New York

ACCOUNT O O H3C

O

H3C

CH3

CH3

NO2

(R)-27

(S,R)-30

ee > 96 %

de = 91 - 92 %, ee > 98 %

ee > 95 % aq. HBF4 (60 %) 95 %

THF, ca. 20 °C O

OSiMe3 CH3

R1

O R2

R2

LDA, THF

CH3 CH3

SiMe2t-Bu

OSiMe3 t-BuMe2Si

NO2 Ar CH2Cl2, SnCl4, t-BuMe2Si - 70 °C

(R)-28

anti : syn = 98:2 - 88:12

O

NH4F / HF O

Ar NO2

74 - 87 %

23

(R,Z)-22

TBAF, THF

81 - 90 %

TMSCl

O

R1

Ph3C+ClO4-

t-BuMe2Si

Ar

57 - 74 %

24

(R)-21

O

t-BuMe2Si

R2

R1

t-BuMe2Si

H3C

1377

a-Silyl Ketone Controlled Asymmetric Syntheses

(R,S,R)-29 de > 96 %, ee > 96 %

( )1,2

, Ph3C+ClO4-

Scheme 10

O OH CH

aq. HBF4 (60 %) O ( )1,2

CH3 CH3 25

3

NH4F, ca. 20 °C ( )1,2 CH3

O

Table 3

SiMe2t-Bu 26

Scheme 9

ever, with moderate to good selectivities (anti : syn = 87:13 - 55:45). The subsequent removal of the silyl group and intramolecular aldol reaction gave bicyclic bhydroxy ketones 26 in good yields (71-75%) without further condensation. Diastereomeric- and enantiomeric excesses, as well as the relative- and absolute configuration, could not be determined. A 1,2-addition did not occur in any cases described. As previously mentioned, enantiopure a-silyl ketones can also be employed in efficient Michael additions to nitroalkenes,26 leading to a-silylated g-nitroketones, which are important intermediates due to the simple transformation of the nitro group into other functionalities.27 Starting from the cyclic silyl ketone (R)-27 (Scheme 10), it was initially converted regioselectively to the corresponding silyl enol ether (R)-28 by deprotonation with lithium diisopropylamide and treatment with chlorotrimethylsilane. Subsequent Michael addition to nitroalkenes was carried out in the presence of SnCl4 as Lewis acid to promote the 1,4-addition reaction. After simple workup and isolation, the silyl nitro ketones 29 were obtained in good yields (74-87%) and with excellent diastereo- and enantiomeric excesses (de, ee > 96%).

The absolute configuration was determined by X-ray structure analysis of crystalline compound 29a (Ar = Ph) as (R,S,R). The cleavage of the carbon-silicon bond with n-Bu4NF and NH4F/HF as a buffer system led to the a,bdisubstituted g-nitro ketones 30 in high yields (81-90%) and very high diastereo- and enantiomeric excesses (de = 91-92%, ee > 98%). However, a partial epimerisation at the a-stereogenic center could not be avoided. The diastereomeric excesses were determined by 1H NMR, the enantiomeric excesses by HPLC on chiral stationary phases. Starting from acyclic silyl ketone 31 for the preparation of the silyl enol ether led to the selectivity problem of E/Zgeometry, which could be solved by the following procedure (Scheme 11). First, the silyl ketone was deprotonated regioselectively with lithium diisopropylamide in the presence of HMPA as a strong cation solvating reagent and treated with Me3SiCl to obtain the pure silyl enol ether 32 in excellent yield (95%). This compound was used for the subsequent 1,4-addition to nitroalkenes, promoted by SnCl4.

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D. Enders et al.

O

O

Ar NO2

CH3 52 - 70 %

t-BuSiMe2 (S)-31

CH3 (R,S)-34

ee > 96 %

de > 96 %, ee > 98 %

LDA, THF / HMPA

95 %

TBAF, THF

80 - 89 %

TMSCl

NH4F / HF

NO2

Ar OSiMe3 CH3 t-BuSiMe2

O

CH2Cl2, SnCl4, - 70 °C 68 - 83%

(S,Z)-32

Ar

first practicable method for the enantioselective synthesis of b-amino ketones was developed by us using enantiopure a-silyl ketones as precursors (Scheme 12).29 The silyl ketones (S)-35 were deprotonated regioselectively with LDA in the presence of HMPA and treated with Me3SiCl to give the corresponding (Z)-silyl enol ethers 36 in quantitative yields. Subsequent aminoalkylation with dibenzylmethoxymethylamine was carried out employing BF3∑OEt2 as Lewis acid to give the a´-silylated b-amino ketones 37 after aqueous workup and flash chromatography in excellent yields (>94%) and diastereomeric excesses (de = 92- ≥ 96%), which could be determined by 1H NMR spectroscopy. The absolute configurations of the Mannich bases were proved by X-ray structure analysis of crystalline compound 37f (R = p-BrPh) as (S,R).

NO2 t-BuSiMe2 CH3 (S,R,S)-33 de > 96 %, ee > 96 %

O

O R

CH3

R

t-HexMe2Si (S)-35

NBn2 CH3

91 - 93 %

(R)-38

ee > 96 %

Scheme 11

ee = 91 - 97 %

Table 4

quant.

LDA, THF / HMPA

TBAF, THF

> 98 %

NH4F

TMSCl Bn2NCH2OCH3 OSiMe3 R

CH3

t-HexMe2Si (S,Z)-36

CH2Cl2, BF3 OEt2, - 95 °C > 94 %

O R

NBn2

t-HexMe2Si

CH3

(S,R)-37 de = 92 - > 96 %

Scheme 12

After simple workup and isolation the a-silylated g-nitro ketones 33 were furnished in good yields (68-83%) and excellent diastereo- and enantiomeric excesses (de, ee > 96%). The removal of the t-butyldimethylsilyl group with n-Bu4NF and NH4F/HF led to the corresponding virtually pure (de > 96%, ee > 98%) a,b-disubstituted g-nitro ketones 34 in very good yields (80-89%) without epimerisation at the a-position.

Table 5

The (R,S)-configuration has been proved by X-ray structure analysis of compound 33a (Ar = Ph), the diastereomeric excesses were determined by 1H NMR spectroscopy and the enantiomeric excesses by HPLC on chiral stationary phases. 3.1.3

Mannich Reactions

A further carbon-carbon bond forming reaction of great interest in organic chemistry is the Mannich reaction, which allows the insertion of an aminomethyl group in aposition to a carbonyl function to give b-amino ketones, which are of interest due to their biological activity.28 The

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Finally, the directing silyl group was removed with nBu4NF and NH4F as a buffer to obtain the b-amino ketones 38 in almost quantitative yields (>98%) and enantiomeric purity (ee = 91 - 97%). The enantiomeric excesses were determined by 1H NMR spectroscopy using (R)-(-)-9-anthryl-2,2,2-trifluoroethanol as a chiral cosolvent.

© Thieme Stuttgart · New York

ACCOUNT

3.1.4

Darzens Reactions

a4-Umpolung Reactions

3.1.5

The Darzens reaction is a useful synthetic protocol for the preparation of biologically active a,b-epoxy ketones30 starting from a-bromo ketones. We have developed an asymmetric version of this reaction31 using enantiopure a´-silylated a-bromo ketones such as 41, which can be easily prepared by the regioselective transformation of the a-silyl ketones (S)-39 to the corresponding trimethylsilyl ethers 40 and reaction with N-bromosuccinimide (NBS). Subsequent addition reaction to aldehydes (Scheme 13), initiated by deprotonation with LDA, leads to the a-bromo-b-alkoxy ketones as intermediates with an anti/syn ratio of ≥98:2. This stereochemical outcome depends on the E-configuration of the lithium enolate, which may be determined by trapping experiments with methyl iodide or trimethylsilyl chloride. The intermediate aldol adducts undergo intramolecular nucleophilic substitution to give the trans-epoxy ketones 42 in good yields (55-80%) and with poor to good diastereomeric excesses (de = 0-90%). The diastereomers may be separated by flash chomatography in all cases to give the diastereomerically and enantiomerically pure a´-silylated a,b-epoxy ketones (de, ee ≥ 95%).

Substituted tetracarbonyl(h3-allyl)iron(1+) complexes are well known to undergo stereo- and g-regioselective addition reactions with a variety of soft nucleophiles to obtain the corresponding allyl coupled products after removal of the stabilizing iron fragment.32 The tetracarbonyl(h3-allyl)iron(1+) complexes undergo nucleophilic attack by the lithiated enantiomerically pure a-silyl ketones 44 leading to 1,6-dicarbonyl compounds 46 (Scheme 14).33 The iron complexes act as a4-synthons via umpolung of the classical d4-reactivity in a (1,5)-homologous Michael addition.

R2

O R3Si

R1 R1

O

O R1

46

(R)/(S)-43

ee = < 5 - > 92 %

ee > 96 %

LHMDS, THF

HBF4 / THF (1:4)

47 - 95 %

7 °C O

R2 R2

R3Si

(S,S,R)-42

OCH3

55 - 80 % TMSCl

OCH3

R

12 - 51 %

45 de = 49 - > 96 %

2. R2CHO,- 95 °C

Scheme 14

3. H2O

OSiMe3

t-BuMe2Si

*

O

1. LDA, THF,- 78 °C

LDA, THF 94 %

CH2

R2

O

(R)/(S)-44

R1

R1

Fe(CO)4 Y R3Si 2. CAN / H2O

1

de = 0 - 90 % de, ee > 95 % after chromatogr.

ee > 95 %

1. H2C

OLi

t-BuMe2Si

(S)-39

OCH3

O

O

CH3

t-BuMe2Si

O

*

R2

- 78 °C

R1

1379

a-Silyl Ketone Controlled Asymmetric Syntheses

O NBS, THF, - 78 °C 85 %

(S)-40 ee > 95 %

Table 7

R1 t-BuMe2Si

Br

(S)-41 ee > 95 %

Scheme 13

Table 6 [a]

[a]

After flash chromatography

Diastereomeric excesses of compounds 45

Initially, the a-silylated ketones 43 were metalated by treatment with lithium hexamethyldisilazide (LHMDS) to give the corresponding lithium enolates 44 with predominantly (Z)-configuration (E/Z: <4 / >96), proved by trapping experiments with trimethyl chlorosilane. Deprotonation of the cyclic silyl ketone 43a (R3Si = tBuMe2Si) led to the lithium enolate 44a of (E)-configuration. The following addition reaction to the methoxySynlett 2000, No. 10, 1371–1384

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carbonyl-substituted tetracarbonyl(h3-allyl)iron(1+) complexes and removal of the iron carbonyl group with ceric ammonium nitrate gave the 1,6-dicarbonyl derivatives 45 in moderate yields (12-51%) and moderate to very good diastereomeric excesses (de = 49 - > 96%), as determined by 13C NMR spectroscopy. In the best cases, desilylation was achieved using a mixture of HBF4 and THF (1:4). Other methods (e.g. TBAF/ THF/H2O, HF/CH3CN) proved to be unsuitable with regard to undesired side reactions. The 1,6-diketones 46 were obtained in moderate to very good yields (35-95%) and poor to excellent enantiomeric purity (ee = <5 - 92%). It is noteworthy, that the dicarbonyl derivatives 45e,f, containing a i-PrMe2Si-group, were desilylated in excellent yields (92-95%) and without remarkable loss of stereochemical purity (ee = 47-66%). Unfortunately, desilylation of compounds containing a t-BuMe2Si-group (45a-d) gave much poorer yields (35-52%). In the case of 45a nearly complete racemisation took place during the prolonged desilylation process (ee < 5%). All enantiomeric excesses described were determined by 1H NMR shift experiments using Eu(tfc)3.

3.2

O

O R2

R1

R2

R1 X

50 ee = 0 - ≥95 %

47

removal of R3Si-group

SAMP/RAMPhydrazone method

O

O R2

R1 SitBuMe2

48 ee ≥95 %

introduction of X

R2

R1 Me2tBuSi

X

49 de ≥95 % X = F, Br, I, OH, NHBoc

Scheme 15

Table 8

Stereoselective Carbon-Hetero Atom Bond Formation

Using a-silylated ketones 8 we have developed methods for the stereoselective synthesis of a-fluoro,34 a-bromo,35 a-iodo,36 a-hydroxy,37 a-amino38 and a-azido ketones.39 Recently a-fluoro ketone derivatives have found application in pharmaceutical and agrochemical research.40 a-Bromo and a-iodo ketones are known as synthetically useful intermediates for the synthesis of a-azido ketones and epoxides.41 a-Azido ketones have been used as intermediates for the synthesis of protected and unprotected aamino ketones42 and a-amino ketones have found wide application as precursors of physiologically important ethanolamine derivatives and a large number of heterocycles.43 Finally, a-hydroxy ketones are common structural features of many natural products and are useful chiral building blocks in the synthesis of biologically active compounds. As shown in Scheme 15 and Table 8, the diastereoselective fluorination of a-silylated ketones 48 with N-fluorosulfonimide (NFSI) gave the a-silylated a-fluoro ketones 49a-c in good yields (59-85%) and with virtually complete diastereoselectivities (de ≥ 95%, after chromatography). Subsequent racemization free carbon-silicon bond cleavage with tetrabutylammonium fluoride (TBAF) in the presence of a buffer mixture (NH4F, KH2PO4 and aqueous HF) led to the corresponding a-fluoro ketones 50a-c in very good yields (99%) and with excellent enantiomeric excesses (ee ≥ 95%). When using N-bromosuccinimide instead of NFSI, the enantiomerically pure a-silylated ketones 48 are converted to the a-silylated a-bromo ketones 49d,e in good yields (80-85%) and with very high diastereoselectivities (de ≥ 95%, after chromatography). To afford the a-bromo keSynlett 2000, No. 10, 1371–1384

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tones 50d,e, the carbon-silicon bond is cleaved using aqueous tetrafluoroboric acid. The cleavage occurred with good yields (63-86%) but with partial racemization of the stereogenic centre (ee = 30 - 35%). a-Silylated ketones 48 are also precursors for the synthesis of a-iodo ketones 50f-h. Therefore, lithium enolates generated in situ of a-silylated ketones 48 are converted with trifluoroiodomethane as iodination reagent to a-silylated a-iodo ketones 49f-h in good to excellent yields (4787%) and with very high diastereoselectivities (de = 95%). Unfortunately, subsequent carbon-silicon bond cleavage using 3HF3∑Et3N, Ph3CBF4 or aqueous or ethereal tetrafluoroboric acid led to complete racemisation. It was not possible to find conditions for racemisation free cleavage. Nevertheless, the first regioselective

© Thieme Stuttgart · New York

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a-Silyl Ketone Controlled Asymmetric Syntheses

synthesis of a-iodo ketones 50f-h was found. The diastereoselective hydroxylation of a-silylated ketones with mchloroperbenzoic acid or 3-phenyl-2-(phenylsulfonyl)oxaziridine, followed by hydrolysis with aqueous HCl and flash chromatography gave the a-silylated a-hydroxy ketones 50i-k of high diastereomeric purity (de ≥ 95%). Subsequent removal of the silyl group without racemization by treatment with aqueous HBF4 (60%) in THF led to the enantiomerically pure a- hydroxy ketones (ee ≥ 95%) in good overall yields (55-70%). Besides several carbon-halogen and carbon-oxygen bond formations we developed two methods for carbon-nitrogen formation starting from a-silylated ketones 48 leading to protected a-amino ketones 50l,m. The conversion of lithium enolates of a-silylated ketones 48 with 3-(4-cyanophenyl)-N-t-butoxycarbonyloxaziridine gave the corresponding a-silylated a-BOC-protected amino ketones 49l,m in moderate yields (27-29%) and with very high diastereoselectivities (de ≥ 95%, after chromatography). Following carbon-silicon bond cleavage using TBAF as cleaving reagent afforded the protected a-amino ketones 50l,m in excellent yields (89-92%). In this case, the cleavage reaction using TBAF was accompanied by partial racemisation at the stereogenic center (ee = 49 - 69%). The a-azido ketones 54 were not synthesized via an electrophilic reaction procedure but via nucleophilic substitution of the iodo group in a-silylated a-iodo ketones 52 using NaN3. The substitution occurred in good yields (4183%) and very high diastereoselectivities (de = 90 ≥95%) with retention of the configuration. The racemisation free carbon-silicon bond cleavage of the resulting asilylated a-azido ketones 53 using 3HF∑Et3N afforded the corresponding a-azido ketones 54 in good yields (5486%) and with very high enantioselectivities (ee = 90 ≥95%; Scheme 16, Table 9).

Table 9

4

Miscellaneous

Besides carbon-carbon and carbon-hetero atom bond formations we have reported further synthetic methods using a-silylated ketones as starting materials. The synthesis of vicinal diols has received considerable interest since they are not only crucial structural features of many biologically active compounds but also important building blocks in organic chemistry.44,45 As shown in Scheme 17 the a-silylated alcohols 56 were synthesized by the reaction of a-2-(isopropoxydimethylsilyl) ketones 55 with L-selectride. Subsequent oxidative cleavage of the carbonsilicon bond according to Tamaos method led to the vicinal diols with retention of the configuration with high diastereo- and enantioselectivities (de ≥ 95%) and high overall yields (52-56%; Table 10). The stereoselectivity of the reduction depends on the silyl ketone, the reducing reagent and the solvent. O R1

OH R2

a)

SiMe2OiPr

OH c)

R1

2

R

R1

SiMe2OiPr

55 ee ≥95 %

R2 OH

57 de, ee ≥95 %

56

R1 = CH3, R2 = CH3, C2H5 O O

O R2

R1

R

R2

1

OH a) or b)

R1

R2 SiMe2OiPr

N3

SiR3

55

54 ee = 90 - ≥95 %

51 1) LDA, 0 °C, 4 h 2) CF3I, inverse addition, −100 °C → rt

OH c)

R1

R2

R1

SiMe2OiPr

ee ≥95 %

R2 OH

57 de, ee ≥95 %

56

For a: R1 ≠ CH3, R2 ≠ CH3, C2H5 For b: R1 = CH3, R2 = CH3, C2H5

3HF•Et3N, THF, 54 - 86 % rt

a) L-Selectride, toluene, −78 °C b) L-Selectride, diethyl ether, SnCl4, −78 °C c) KF, KHCO3, 30 % H2O2 aqueous solution, MeOH/THF

O

O R2

R1

NaN3, rt

R2

R1

Scheme 17

41 - 83 % SiR3

I

52 de ≥ 95 %

SiR3 N3 53

Table 10

de = 90 - ≥95 %

Scheme 16

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Allylsilanes are extremely useful intermediates in organic synthesis, especially as important carbon nucleophiles in reactions with a wide variety of electrophilic reagents in a highly regio- and stereoselective manner.2,46 Starting from silyl aldehydes 58, allylsilanes 59 of high enantiomeric purity (ee = ≥95%) were synthesized via Wittig olefination with various alkylidene triphenylphosphoranes in high E/Z selectivities (94/6 - 97/3) in good yields (8092%) and without racemisation (Scheme 18, Table 11).

Table 12

R2CH2PPh3X, n-BuLi, THF, −78 °C 40 - 92 % R2

SitBuMe2

O

SitBuMe2

R1

R1

58

59

ee = 90 - ≥95 %

ee = 90 - ≥95 % 1) O3, CH2Cl2, −78 °C 2) Me2S, CH2Cl2, −78 °C

chiral vicinal silylamines (Scheme 19).47 Nucleophilic 1,2-addition of in situ prepared methyl cerium reagent to a-silyl aldehyde-SAMP-hydrazone 2 and subsequent reductive nitrogen-nitrogen bond cleavage affords protected vicinal silylamines 3 in good yields (56-78%) with high diastereomeric and enantiomeric excesses (de, ee ≥95%; Table 12).

75 - 80 %

Scheme 18

5

Application of a-Silyl Controlled Asymmetric Syntheses

5.1

Pheromone Synthesis

Table 11

Ozonolysis of the allylsilanes, followed by reductive workup with dimethylsulfide led back to the corresponding a-silyl aldehydes without racemisation. As mentioned above, chiral amines are important intermediates for the synthesis of bioactive compounds. Based on our silyl ketone method we have reported the synthesis of

Insect pheromones48 belong to the class of semiochemicals. They are chemical messengers, which are secreted by an insect and received by another individual of the same species. The reception of the pheromone leads to a specific reaction, e.g. aggregation, sexual behavior etc. In 1984 Burkholder et al. reported on the isolation of the aggregation pheromone of the rice and maize weevil, sitophilure.49 It was identified to be syn-5-hydroxy-4-methyl3-heptanone. The absolute configuration was determined by the comparison of acetyl lactate derivatives of natural and synthetic samples and was determined to be >98% (4S,5R) in case of the maize weevil and >92% (4S,5R) in case of the rice weevil.50

O H3C

O H3C

H 60

36-49 %

SAMP/RAMPhydrazone method

49-72 %

NH

R

H3C

CH3

SiMe2tBu (R,S)-63 de, ee = ≥95 % 78-88 %

H3CO

CH3

N R

H SiMe2tBu

1) CH3Li/CeCl3, THF, F3C −100 °C R 2) (CF3CO)2O 70 - 91 %

(S,S)-61 de ≥95 %

CHO

N

CH3

(S)-13

(4S,5R)-16b de > 98 %, ee > 98 %

H3C

OCH3

H3C

CHO

62 % (R)-13

SiMe2tBu

OH

H3 C

CH3 CH3 (4R,5S)-16b

de > 96 %, ee > 98 %

de = 90 - ≥95 %

Scheme 20 ISSN 0936-5214

O CH3

t-BuMe2Si

CH3

(S,R,S)-62

CH3

58 %

1) Li/NH3,t-BuOH, THF, −33 °C 2) AcCl, py

N

OH

H3 C

O

Scheme 19 Synlett 2000, No. 10, 1371–1384

H3C

t-BuMe2Si

O N

O

O

© Thieme Stuttgart · New York

ACCOUNT

We have developed an efficient method for the asymmetric synthesis of both enantiomers of sitophilure using enantiopure a-silyl ketones as nucleophilic components in an asymmetric aldol reaction,22 which was presented in section 3.1.1 (Scheme 7). Reaction of (S)-13 or (R)-13 with propioaldehyde (R = Et) led after removal of the silyl group to the natural Sitophilure (4S,5R)-16b or its enantiomer (4R,5S)-16b (Scheme 20) in good overall yields (5862%) and excellent diastereo- and enantiomeric excesses (de ≥ 96%, ee ≥ 98%).

O

O

R

O

H SiMe2t-Bu

OMe SiMe2t-Bu

27 -28 %

(S)-64

(S,R,S)-67 de = > 96 %, ee = 93 - > 96 %

TMSO

MeC(OMe)2Me

OTMS

54 - 87 %

90 %

BF3 OEt2, CH2Cl2

Synthesis of Mevinolin Analogues

The 1,3-diol functionality is of great importance for the bioactivity of many pharmaceutical products, such as HMG-CoA-reductase-inhibitors or macrolide antibiotics. Therefore, it is not surprising that a great deal of different strategies have been developed for the stereoselective synthesis of compounds containing a 1,3-diol functionality.51 We have synthesized 6-silyl substituted-3,5-dihydroxyesters using a high diastereo- and enantioselective aldol reaction of enantiomerically pure a-silyl aldehydes (S)-64 to 1,3-bis(trimethylsilyloxy)-1-methoxybutadiene as the key step (Scheme 21).52 The a-silyl aldehydes 64 were activated by treatment with titanium tetrachloride. Subsequent aldol reaction led to the 6-silyl substituted 5hydroxy-3-oxoesters 65 as single diastereomers in moderate to good yields (54-87%). The subsequent syn-selective reduction of the keto group with tributylborane / pivalic acid / sodium borohydride yielded the syn-diols 66 in moderate yields (52-55%). After protection of the diol functionality with 2,2-dimethoxypropane in the presence of BF3∑OEt2 the corresponding acetonides 67 were obtained in very good yields (90%) and excellent diastereoand enantiomeric excesses (de > 96%, ee = 93-95%). The diastereomeric excesses were determined by 13C NMR spectroscopy, the enantiomeric excesses by 1H NMR spectroscopy using (R)-(-)-9-anthryl-2,2,2-trifluoroethanol as chiral cosolvent. The synthesized protected 6-silyl substituted-3,5-dihydroxy esters 67 are interesting intermediates, which offer an efficient entry to new precursors for the synthesis of mevinolin analogues.

6

O

R

OMe

5.2

1383

a-Silyl Ketone Controlled Asymmetric Syntheses

Conclusion

In this account we have described a series of methodologies in asymmetric synthesis employing enantiopure a-silyl ketones and aldehydes, which have been developed by us in recent years. We hope that this review gives the readership an insight into the numerous applications of a-silyl ketone controlled asymmetric reactions and demonstrates the virtually complete asymmetric inductions possible with the “traceless“ silyl directing group.

OH

O

Bu3B,

O

R

OMe SiMe2t-Bu

C4H9CO2H, NaBH4 52-55 %

OH

OH

R

O OMe

SiMe2t-Bu (S,R,S)-66

(S,R)-65

Scheme 21

Table 13

References and Notes (1) Enders, D.; Klatt, M. In Encyclopedia of Reagents for Organic Synthesis; Paquette, L.A., Ed.; Wiley: New York, 1995; p 178. Enders, D. In Asymmetric Synthesis, Vol. 3; Morrison, J.D., Ed.; Academic Press: Orlando, 1984, p 275. (2) Larson, G.L. Adv. Silicon Chem. 1996, 3, 105. Colvin, E.W. Silicon Reagents in Organic Synthesis; Academic Press: New York, 1988. (3) Hauser, C.R.; Hance, C.R. J. Am. Chem. Soc. 1952, 74, 5091. (4) Demuth, M. Helv. Chim. Acta 1978, 61, 3136. (5) Seitz, D.E.; Zapata, A. Synthesis 1981, 557. (6) Larson, G.L.; de Lopez-Cepero, I.M.; Tores, L.-E. Tetrahedron Lett. 1984, 25, 1673. (7) Sato, S.; Okada, H.; Matsuda, I.; Izumi, Y. Tetrahedron Lett. 1984, 25, 769. Beißwenger, H.; Hanack, M. Tetrahedron Lett. 1982, 23, 403. Fristad, W.E.; Bailey, T.R.; Paquette, L.A. J. Org. Chem. 1980, 45, 3028. Yamamoto, K.; Tomo, Y.; Suzuki, S. Tetrahedron Lett. 1980, 21, 2861. Obayashi, M.; Utimoto, K.; Nozaki, H. Bull. Chem. Soc. Jpn. 1979, 52, 1760. Obayashi, M.; Utimoto, K.; Nozaki, H. Tetrahedron Lett. 1977, 18, 1807. Eisch, J. J.; Galle, J.E. J. Org. Chem. 1976, 41, 2615. Hudrlik, P.F. Tetrahedron Lett. 1976, 17, 1453. Hudrlik, P.F.; Peterson, D. J. Am. Chem. Soc. 1975, 97, 1464. (8) Gilloir, F.; Malacria, M. Tetrahedron Lett. 1992, 33, 3859. (9) Cunico, R.F. Tetrahedron Lett. 1986, 27, 4269. (10) Corey, E.J.; Rücker, C. Tetrahedron Lett. 1984, 25, 4345. (11) Duhamel, L.; Gralak, J.; Bouyanzer, A. J. Chem. Soc., Chem. Commun. 1993, 1763.

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