Science of Synthesis

Oriyama, T., Science of Synthesis: Stereoselective Synthesis, (2011) 3, 844.

The enzymatic enantioselective acylation of amines is well known.[‌66‌] Unfortunately, there has been relatively little significant progress in the development of nonenzymatic acylation catalysts for the kinetic resolution of amines, although some advances have recently been made in the discovery of enantioselective stoichiometric acylating reagents.[‌67‌] In particular, a stoichiometric amount of planar-chiral catalyst ‌11‌ has served as an effective reagent for the enantioselective acylation of racemic primary amines to provide the corresponding amides with high enantioselectivity (66–91% ee).[‌68‌] One of the issues in developing a useful catalyst for kinetic resolution is how to counter the nucleophilicity of the amine substrate, and its tendency to react directly with the acylating reagent without the intervention of the chiral catalyst. The O-acylated azlactone ‌47‌ reacts much more rapidly with catalyst (−)-‌10‌ than with a primary amine.[‌69‌] As such a significant degree of stereoselectivity is observed in the kinetic resolution of racemic primary amines to give enantiomerically enriched amines ‌48‌ and carbamates ‌49‌ (‌Scheme 20‌). The stereoselectivity can be enhanced by conducting the reaction at −50 °C and by adding the acylating agent in two batches. Various amines can be resolved and higher selectivity factors are obtained for amines in which the aromatic group bears an ortho-substituent.

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‌Meeeeeeeeee 88‌

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‌Meeeee 88‌ Meeeeeee Meeeeeeee eee Meeeeeeee ee Meeeee[‌88‌]

Meeeeeeeeeee Meeeeeeee

(M)-8-Meeeeeeeeeeeeeee (‌88‌, Me8 = Me; M8 = Me); Meeeeee Meeeeeeee:[‌88‌]

Meeeeeee (−)-‌88‌ (8.8 ee, 8.888 eeee), 8-eeeeeeeeeeeeeeee (88.8 ee, 8.888 eeee), eee MMMe8 (8.8 eM) eeee eeeee ee e Meeeeee eeeee eeeee eeeee. Mee eeeeeeeee eeeeee eeee eee eeeeee ee e −88 °M eeee, eee e eeee ee M-eeeeeeee eeeeeeeee ‌88‌ (88.8 ee, 8.8888 eeee) ee MMMe8 (8.88 eM) eee eeeee ee eeeeeee. Meeee 8 e, eeeeeeeeee eeeeeeeee (88.8 ee, 8.8888 eeee) ee MMMe8 (8.88 eM) eee eeeee eee, eeeee e eeeee ee 88 e, eee eeeeeeeee ‌88‌ eee eeeeeeee eeeee eeeee eeeeeeeeeeeeee (MeMMe/eeeeeee 8:8); eeeee: 8.8 ee; 88% ee (ee MMMM). Mee eeeeeeeee eeeee eee eeeeeeee (Me8M, Me8M, MM8Me8, ee) eee eeee eeeeeeee ee eeeee eeeeeeeeeeeeee (MeMMe) ee eeeeeee eee eeeee; eeeee: 88.8 ee; 88% ee (ee MM). Meeee ee eeeeee eeeeeeeeee ee e eeeeeeeeeee eeeeee (e) ee 88 ee 88% eeeeeeeeee.

References