Bislactim ethers unsaturated esters

An excellent method for the diastereoselective synthesis of substituted amino acids is based on optically active bislactim ethers of cyclodipeptides as Michael donors (Schollkopf method, see Section 1.5.2.4.2.2.4.). Thus, the lithium enolates of bislactim ethers, from amino acids add in a 1,4-fashion to various a,/i-unsaturated esters with high diastereofacial selectivity (syn/anti ratios > 99.3 0.7-99.5 0.5). For example, the enolate of the lactim ether derivative 6, prepared from (S)-valine and glycine, adds in a highly stereoselective manner to methyl ( )-3-phenyl-propenoate a cis/trans ratio of 99.6 0.4 and a syn/anti ratio of 91 9, with respect to the two new stereogenic centers, in the product 7 are found105, los. 

Ail extremely useful method for the asymmetric synthesis of substituted amino acids, in particular glutamic acids, is based on optically active bislactim ethers of cyclodipeptides. The lithium etiolates of bislactim ethers (which are prepared easily from amino acids) undergo 1,4-addition to various a,/ -unsaturated esters to give -substituted 2,5-dihydropyrazine-propanoates203-205 with high diastereofacial selectivity, ratio (R/S) > 140-200 1. 

In a further extension of this method, the enolate of the bislactim ether cyclo(L-Val-Gly) or cyclo(L-Val-Ala) were added to methyl (Z)-3-chloro-2-butenoate. The adduct is again a (Z)- ,/l-unsaturated ester and was obtained as a single diastereomer (d.r. > 99 l)207. For further examples see references cited ill the text. 

Reaction of the Titanated Bislactim Ether. The titanium derivative of the bislactim ether of cyclo(L-Val-Gly) reacts with alkyl aldehydes, aryl aldehydes, and a,(3-unsaturated aldehydes highly diastereoselectively to give almost exclusively the syn addition products (eq 2). Hydrolysis with dilute Trifluo-roacetic Acid affords (2R, 35 )-(3-hydroxy-a-amino acid methyl esters. a-Amino-y-nitro amino acids can be obtained by 1,4-addition of the titanated bislactim ether to nitroalkenes and subsequent hydrolysis of the adduct. ... 

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