Merging Gold and Organocatalysis: A Facile Asymmetric Synthesis of Annulated Pyrroles

Abstract

The combination of cinchona-alkaloid-derived primary amine and AuI–phosphine catalysts allowed the selective C–H functionalization of two adjacent carbon atoms of pyrroles under mild reaction conditions. This sequential dual activation provides seven-membered-ring-annulated pyrrole derivatives in excellent yields and enantioselectivities.

Gold(I)-Catalyzed Activation of Alkynes for the Construction of Molecular Complexity

“…The one-pot asymmetric synthesis of annulated pyrroles 455 has recently been reported combining cinchona-alkaloid-derived primary amine and gold(I) catalysts (Scheme 148 ). 403 …”

Recent Advances in Metal‐ and Organocatalyzed Asymmetric Functionalization of Pyrroles

“…In 2014, Enders and co-workers developed a highly efficient and straightforward one-pot multi-catalytic strategy for the enantioselective cascade reaction of pyrroles 11 to enones 159 (Scheme 56). [125] With the help of a synergic combination of 20 mol% of cinchona-alkaloid-derived primary amine C-37 and 10 mol% of Au I -phosphine catalysts C-38, a series of sevenmembered-ring annulated pyrrole derivatives 160, derived via the sequential Friedel-Crafts type Michael addition and 7-endodig cyclization, were obtained in moderate to excellent yield with high enantioselectivity. This dual activation facilitates the selective CÀ H functionalization of two adjacent carbon atoms of pyrroles under mild reaction conditions.…”

“…However, the proper choice of dual catalytic system and the reactants compatibility for the one-pot systems are major hurdles as the products were not acquired using either the catalysts alone. [127] Similar to Ender's work as described in Scheme 56, [125] which involves the synthesis of 7-membered annulated pyrroles via merging organocatalysis and gold catalysis, an alternative onepot sequential cascade strategy for the synthesis of annulated pyrroles through the combination of the dual metal catalytic system has been developed by Wang and co-workers in 2015. This sequential tandem reaction proceeds through the Cucatalyzed initial Friedel-Crafts alkylation between pyrroles 1 to β,γ-unsaturated α-ketoesters 164, and gold-catalyzed 7-endodig annulation step (Scheme 59).…”

Asymmetric Synthesis of Spiropyrazolones by Sequential Organo‐ and Silver Catalysis

“…[3] Our group has become interested by the combination of transition-metal and organocatalysis for the asymmetric synthesis of annulated heterocycles. [4] Although we originally focused our investigations on gold catalysis, [5] we have been recently intrigued by silver catalysis and its largely untapped potential in sequential and relay catalysis. [6][7][8] Ag I salts represent an inexpensive alternative to other carbophilic transition metals commonly used for the electrophilic activation of alkynes such as gold or platinum.…”