Aldehydes, asymmetric alkylation dialkylzinc reagents

An amino alcohol was found to accelerate the addition reaction of diethlylzinc to aldehyde [8], and then chiral amino alcohols were proved to be efficient chiral catalysts for asymmetric alkylation by using dialkylzinc reagents [9], Oguni reported a remarkable asymmetric amplification in chiral amino alcohol-promoted alkylation (Scheme 9.4). In the presence of (-)-l-piperidino-3,3-dimethyl-2-butanol (5) of 11% ee, benzaldehyde is alkylated enantioselectively to give (/ )-l-phenylpropanol with 82% ee [10]. Asymmetric amplification was also observed by Noyori using partially resolved (2.S )-3-exo-(dimethylamino)isobomeol (6) [11]. 

The asymmetric alkylation of aldehydes by dialkylzinc reagents is one of the most intensively studied catalytic reactions [60-62]. Following the initial discoveries of Oguni and colleagues, including the recognition that a single... 

Introduction. (1 R,25, 3/ ,45 )-3-Dimethylamino-1,7,7-trime-thylbicyclo[2.2.1 ]heptan-2-ol, herein referred to as (—)DAIB, has been shown to be an effective catalyst for enantioselective carbon-carbon bond formation utilizing dialkylzinc reagents with aldehydes and ketones. Attempts to utilize (—)DAIB for asymmetric inductions with other organometallic reagents such as aluminum alkyls, alkyl Grignards, and alkyl lithiums, have been unsuccessful. ... 

In the asymmetric alkylation of a-chiral aldehydes using dialkylzinc reagents, the stereochemistry is controlled by the configuration of the chiral catalyst, not by the stereochemistry in the a-position. It is different from the diastereoselec-tive alkylation using other organometallic reagents where the stereochemistry follows from Cram s rule or the Felkin-Ahn model. Each diastereomer with high ee was obtained by the choice of the appropriate enantiomer of chiral catalyst [(IS, 2R)- or (li ,2S)-DBNE 1] (Scheme 6) [18]. 

The addition of dialkylzinc to aldehyde proceeds smoothly in the presence of a Lewis acid. Several catalytic asymmetric alkylations catalyzed by chiral titanium complexes have been reported using dialkylzinc reagents. 

In this section, the asymmetric synthesis of the vicinal thio- and selenoalcohols 42 — 45 is described based on the highly enantio- and diastereoselective addition of diethylzinc reagent to racemic a-thio- and selenoaldehydes 41, catalyzed by 20o (( —)-DFPE) and S,R)-2Qo ((+)-DFPE) (Scheme 3-20). Although the enantio-selective addition of dialkylzinc reagents to achiral aldehydes using chiral catalysts has been well investigated [10], there are no known catalytic enantio- and di-asteroselective dialkylzinc additions to aldehydes with chiral centers, except for the alkylation of a-methyl- [58, 59], a-chloro- [59], and j5-alkoxyaldehydes [60]. The reaction of diethylzinc with racemic a-thio- and selenoaldehydes 41 was carried out in the presence of 20o or (S,il)-20o (5 — 50 mol%) in hexane at room temperature for 12 —16h. The results are summarized in Table 3-11. 

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