Reformatsky reaction spartein

The earliest enantioselective Reformatsky reaction was reported in 1973.52 Compound (-)-spartein was used as the chiral ligand, but the reaction gave rather low yield. Almost 20 years later, in 1991, Soai and Kawase53 reported an enantioselective Reformatsky reaction in which chiral amino alcohol 58 or 59 was used as the ligand. Aliphatic and aromatic //-hydroxy esters were obtained with moderate to good yields. 

The indium-induced Reformatsky reaction with stoichiometric amounts of chiral amino alcohols such as cinnco-nine and cinchonidine gives optically active /3-hydroxy esters with 40%-70% ee (Table 19). In contrast to the smooth reaction with uncomplexed indium-based Reformatsky reagents, ketones do not react with the complexed indium Reformatsky reagents. Other chiral ligands, including (—)-spartein, (—)-norephedrine, (+)-(l-methylpyrrolidin-2-yl)diphenylmethanol, (+)-Dibutyl tartrate and (+)-l,l -bi-2-naphthol, are not effective for this reaction.324... 

Chiral Modification of Achiral Organometallic Reagents. The addition of n-Butyllithium or Ethylmagne-sium Bromide to aldehydes or ketones in the presence of (—)-sparteine resulted in the formation of optically active secondary or tertiary alcohols with 20% ee or lower. Optically active acyl sulfoxides (<15% ee) were obtained by acylation of p-Tolylsulfinylmethyllithium. The asymmetric Reformatsky reaction of ethyl bromoacetate with benzaldehyde proceeds with 95% ee, in an exceptional case (eq 1). ... 

Details have been given of the partial asymmetric syntheses of j -hydroxy-esters by the Reformatsky reaction in the presence of (— )-sparteine, reported in brief earlier. The optical purity of the products was occasionally very high, particularly when the carbonyl component was benzaldehyde, and reached 95 3 % in the reaction between benzaldehyde, zinc, sparteine, and ethyl bromo-... 

The ability of ditertiary bases of the sparteine group to complex with alkali-metals and alkaline-earth metals has been further investigated by carrying out the Reformatsky reaction in the presence of ( —)-sparteine. In all the cases examined, a partial asymmetric synthesis of (S)-hydroxy-esters was achieved, the optical purity of the products ranging from 34—98 %. 

The Reformatsky reaction, the zinc-mediated reaction of a-halo esters with aldehydes or ketones, may be considered an alternative to the aldol addition. As far as enantioselective versions are concerned, this method was much less developed than the aldol protocols [155]. In an early approach, Guette and coworkers explored the Reformatsky reaction of ethyl bromoacetate in the presence of stoichiometric amounts of sparteine although a high enantiomeric excess was observed with benzaldehyde (94% ee), the method was much less satisfactory for other carbonyl compounds [156]. According to a report of Yamano and coworkers, high enantioselectivity (up to 97% ee) was obtained when the Reformatsky reagent generated from ethyl bromoacetate was allowed... 

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