A Robust, Efficient, and Highly Enantioselective Method for Synthesis of Homopropargyl Amines

摘要

Catalytic protocols that generate α-branched amines efficiently and enantioselectively facilitate the preparation of many important biologically active molecules. Among such entities are homopropargyl amines, used in the total synthesis of a number of natural products.Several investigations have adopted the chiral auxiliary strategy; the desired products are obtained in high diastereoselectivity as trimethylsilyl-substi-tuted alkynes. In contrast, the corresponding catalytic protocols are scarce. The first relevant report included three examples of reactions of allenyl stannanes with a glyoxylate-derived tosylimine,affording homopropargyl sulfonamides in 34-96 yield and 55:45-93:7 enantiomeric ratio (e.r.). A notable recent advance entails enantioselective additions of a readily available allenylboron to tosylimines catalyzed by a Ag-phosphine catalyst to furnish a wider range of products and higher enantioselectivity (87:13 to more than 98:2 e.r.). Nonetheless, reactions of substrates that do not bear an aryl substituent proved to be less efficient, those of enolizable alkyl-substituted tosylimines were not reported and, as with the aforementioned initial development, removal of the tosyl unit requires strong reducing conditions.