FAM-Ag-catalyzed asymmetric synthesis of heteroaryl-substituted pyrrolidines.

New derivatives of FAM (ferrocenyl aziridinyl methanol) ligands NFAM1-4 (naphthyl ferrocenyl aziridinyl methanol) and CFAM1-4 (cyclohexyl ferrocenyl aziridinyl methanol) were synthesized to form a small ligand library and used as chiral catalysts with AgOAc for the asymmetric synthesis of heteroaryl-substituted pyrrolidines by the 1,3-dipolar cycloaddition (1,3-DC) reaction of azomethine ylides. 2-Thienyl, 2-furyl, 2-, 3-, and 4-pyridyl aldimines were prepared and used with N-methylmaleimide, dimethyl maleate, tert-butyl acrylate, methyl acrylate, and acrylonitrile to form the corresponding heteroaryl-substituted pyrrolidines. 1,3-DC reactions yielded the expected cycloadducts in up to 89% yield and up to 76% ee that could be increased up to 95% ee upon crystallization.

Evidence for pi-stacking as a source of stereocontrol in the synthesis of the core pyranochromene ring system common to calyxin I, calyxin J, and epicalyxin J.

A diastereoselective synthesis of the tetrahydropyranochromene ring system common to several natural product isolates of Alpinia blepharocalyx is reported. We have shown that a stereochemical preference exists for a syn configuration between the anomeric aryl substituents, representative of the C-7 and C-7' substituents in the natural products. Further, our results show that stereocontrol is under kinetic control, and calculations suggest that a favorable pi-stacking interaction may be the source of this stereocontrol.

Stereoselective approach to C-aryl pyranoside synthesis which addresses the problem of C7-substitution in blepharocalyxin E.

A general route to a series of aryl-substituted pyranoside derivatives has been developed as a model for the synthesis of blepharocalyxin E. Two exo-substituted tetrahydro-4H-furo[2,3-b]pyran-2-one derivatives, 8a and 8b, were prepared and treated separately with anisole and phenoxytriisopropylsilane under Lewis acid conditions to effect C-aryl pyranoside synthesis. In each case, a gamma-lactone was formed, which rearranged to the desired structure on acid treatment.