Alcohols enantioselective synthesis, from aldehyd

Since the addition of dialkylzinc reagents to aldehydes can be performed enantioselectively in the presence of a chiral amino alcohol catalyst, such as (-)-(1S,2/ )-Ar,A -dibutylnorephedrine (see Section 1.3.1.7.1.), this reaction is suitable for the kinetic resolution of racemic aldehydes127 and/or the enantioselective synthesis of optically active alcohols with two stereogenic centers starting from racemic aldehydes128 129. Thus, addition of diethylzinc to racemic 2-phenylpropanal in the presence of (-)-(lS,2/ )-Ar,W-dibutylnorephedrine gave a 75 25 mixture of the diastereomeric alcohols syn-4 and anti-4 with 65% ee and 93% ee, respectively, and 60% total yield. In the case of the syn-diastereomer, the (2.S, 3S)-enantiomer predominated, whereas with the twtf-diastereomer, the (2f ,3S)-enantiomer was formed preferentially. 

The enantioselective synthesis in Scheme 13.22 is based on stereoselective reduction of an a, (3-unsaturated aldehyde generated from (—)-(.V)-limonene (Step A). The reduction was done by Baker s yeast and was completely enantioselective. The diastereoselectivity was not complete, generating an 80 20 mixture, but the diastere-omeric alcohols were purified at this stage. After oxidation to the aldehyde, the remainder of the side chain was introduced by a Grignard addition. The ester function... 

In addition to the results described, enantioselective access to 2-phosphino alcohols could be accomplished, too [71]. Starting from a borane-protected a-phosphino aldehyde hydrazone 91 as the key intermediate and available by two different approaches, the enantioselective synthesis of the desired 2-phosphino alcohols 93 could be accomplished. Thus, the electrophilic phosphinylation of aldehyde hydrazones 90 (via route I with the chlorodiphenylphosphine-borane adduct or via route II with chlorophosphines and subsequent phosphorus-boron bond formation) and the alkylation of phosphino acetaldehyde-SAMP hydrazones 92 (route III) was carried out (Scheme 1.1.26). 

Chirality plays a central role in the chemical, biological, pharmaceutical and material sciences. Owing to the recent advances in asymmetric catalysis, catalytic enantioselective synthesis has become one of the most efficient methods for the preparation of enantiomer-ically enriched compounds. An increased amount of enantiomerically enriched product can be obtained from an asymmetric reaction using a small amount of an asymmetric catalyst. Studies on the enantioselective addition of dialkylzincs to aldehydes have attracted increasing interest. After the chiral amino alcohols were developed, highly enantioselective and reproducible —C bond forming reactions have become possible. 

Chiral homoallylic alcohols, The glycol 1 has been used as the chiral matrbt in an enantioselective synthesis of homoallylic alcohols (4) from aldehydes and allyl-boranes (equation I). 

Roush, W. R., Grover, P. T. Diisopropyl tartrate (E)-Y-(dimethylphenylsilyl)allylboronate, a chiral allylic alcohol 3-carbanion equivalent for the enantioselective synthesis of 2-butene-1,4-diols from aldehydes. Tetrahedron Lett. 1990, 31,7567-7570. 

Panek et al. introduced the synthesis of optically active crotylsilanes by Claisen rearrangement of allyl vinyl ethers derived from homochiral y-silylated allyl alcohols (Scheme 10.141) [393]. These allylsilanes have been used for highly diastereo-and enantioselective allylation of aldehydes and acetals [334], which enables efficient syntheses of complex natural products [394]. 

Synthesis from o-glyceraldehyde Synthesis of (-)-prosophylline (1) from D-glyceraldehyde acetonide (64) has been reported (Scheme 7). The enantioselective al-lylation of aldehyde 64 with (S,S)-75 afforded the homoallyl alcohol 65 in 86% yield. Protection of 65, as the benzyl derivative, followed by hydroboration and transformation to... 

This reaction was first reported by Roush in 1985. It is an enantioselective synthesis of a chiral alcohol by the condensation between a crotylboronate derived from diisopropyl-(/ ,/ )-tartrate and an achiral aldehyde. Therefore, it is known as the Roush crotylboration, ... 

Sulfonamide 79f (10 mol%. Scheme 4.29) allowed the enantioselective synthesis of convolutamydine E (89c) and derivatives, by the reaction of isatins (72) and acetaldehyde (5f) in THE at 25°C, followed by reduction with NaBHjCN. As in the previous cases, isatin 72a gave the corresponding alcohol in moderated yield (60%) and nearly as a racemic mixture. Other linear aldehydes different from acetaldehyde, gave alcohols 89 with good results, while the reaction with a-branches aldehydes failed [156]. 

An intermolecular FC hydroxyalkylation on a carboxonium ion is the key step in the enantioselec-tive synthesis of the nenrotrophic lignan (-)-talaumidin (Scheme 2.5) [6]. The carboxonium precursor 36 was prepared from alcohol 33 (obtained in eight steps from aldehyde 32 with high diastereo- and enantioselectivity). The crucial diastereoselective FC step was achieved upon treatment of 36 with 1,2-methylenedioxybenzene (37) and SnCl, which afforded straightforwardly the desired product 39 in 89% yield throngh cation 38. Debenzylation of 39 with Pd(OH)2 fnmished (-)-(2S,3S,4S,5S)-talaumidin (40) in 77% yield. 

Alkylations Chiral amino alcohol-functionaUzed polystyrene resins [36, 37] were useful catalysts in the enantioselective alkylation of aldehydes with diethyl zinc in continuous-flow columns. Another continuous flow system for the synthesis of enantioenriched diarylmethanols from aldehydes used transmetallation of tti-arylboroxins with diethyl zinc over amino alcohol-functionaUzed polystyrene resin catalyst [38]. 

On the other hand, however, trimethylsilyl-protected catalyst 18 was suitable for the asymmetric bromination of aldehydes, and the resulting a-bromoaldehydes can be diastereoselectively transformed into the corresponding bromohydrin in one-pot (Scheme 7.31) (54). An additional utility of catalyst 18 was highlighted by application to the development of the direct aminoxylation of aldehydes with an oxoammonium salt generated from 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) by in situ oxidation with benzoyl peroxide, allowing for the highly enantioselective synthesis of stable a-aminoxy aldehydes, which could subsequently be reduced to the corresponding alcohol (55). 

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