Alkylations of azaenolates

In comparison to the alkylation reactions noted above, stereoselective alkylations of azaenolates derived from chiral auxiliaries and carbonyl compounds are more flexible concerning the variability of alkylation products. 

Despite the highly selective alkylations of azaenolates, the optical purity of the final products is rather low in several cases, due to partial racemization during hydrolysis of the alkylated imines. In general, racemization occurs very fast in basic media, whereas in acidic solutions, especially in two-phase systems, the degree of racemization is rather low and depends on the nature of the carbonyl compounds. 

P. Fey, Alkylation of Azaenolates from Imines, in Stereoselective Synthesis (Houben-Weyl) 4th ed. 1996, (G. Helmchen, R. W. Hoffmann, J. Mulzer, E. Schaumann, Eds.), 1996, Vol. E 21 (Workbench Edition), 2, 973-993, Georg Thieme Verlag, Stuttgart. 

As a close analog to 1-phenylethylamine but possessing greater steric hindrance, (5)-l-naph-thylethylamine has been employed as an auxiliary for the alkylation of azaenolates via imines (Section D. 1.1.1.4.) and amides (Section D.1.5.1.). The racemate (obtained by reductive amina-tion of 1-acetylnaphthalene) is best resolved w ith tartaric acid16 (see also ref 17). 

An amino ether 46, presumably derived from (+)-3-carene [( + )-40], has been used for asymmetric alkylation of azaenolates via imines (SectionD.1.1.1,4.1., ref 40). No details were given on the synthesis of 46, but it can be prepared by methylation of the corresponding amino alcohol which was probably obtained from the epoxide of ( + )-3-carene by ring opening with trimethylsilyl azide, followed by catalytic hydrogenation41,... 

Conclusion After the chiral hydrazones developed by Enders, Evans introduced the chiral oxazoUdinones, which tpeared to be particularly useful not only for the diastereoselective alkylation of azaenolates but also on a wide range of asymmetric transformations, finding applications in the synthesis of some of the most architecturally appealing and complex natural products. 

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