Enantioselectivity
and Reactivity Enhancement by 1,1,3,3-Tetramethylguanidine
in Bisguanidinium-Catalyzed Asymmetric Alkylation for Construction
of Indole Alkaloid Marine Natural Products
Catalytic 1,1,3,3-tetramethylguanidine (TMG)-mediated
enhancement
of enantioselectivity and reactivity was revealed in bisguanidinium-catalyzed
asymmetric prenylation, propargylation, and benzylation of 3-substituted
oxindoles. Preliminary mechanistic studies indicate that protonated
TMG not only assists enolate intermediate formation as a phase-transfer
agent but also activates electrophiles in the transition state. The
resulting 3,3-disubstituted oxindoles with high enantioselectivities
were readily transformed to pharmaceutically valuable molecules. A
mild and efficient methodology for synthesizing (−)-flustramine
B, (−)-debromoflustramine B and their triazole analogues with
antibiofilm potentials was established.