An enantioselective total synthesis of martinellic acid is described. The pyrroloquinoline alkaloid core is efficiently prepared from a quinoline, employing a method which relies on a newly developed Cu-catalyzed enantioselective alkynylation using the chiral imidazole-based biaryl P,N ligand StackPhos to establish the absolute stereochemistry. The remaining carbon atoms are then installed by means of a diastereoselective Pd-catalyzed decarboxylative allylation and the synthesis is completed after straightforward functional-group manipulation. This new synthetic method enables the most concise enantioselective synthesis of this important class of molecules to date.

A highly enantioselective copper-catalyzed alkynylation of quinolinium salts is reported. The reaction employs StackPhos, a newly developed imidazole-based chiral biaryl P,N ligand, and copper bromide to effect a three-component reaction between a quinoline, a terminal alkyne, and ethyl chloroformate. Under the reaction conditions, the desired products are delivered in high yields with ee values of up to 98 %. The transformation tolerates a wide range of functional groups with respect to both the alkyne and the quinoline starting materials and the products are easily transformed into useful synthons. Efficient, enantioselective syntheses of the tetrahydroquinoline alkaloids (+)-galipinine, (+)-angustureine, and (−)-cuspareine are reported.

An enantioselective total synthesis of martinellic acid is described. The pyrroloquinoline alkaloid core is efficiently prepared from a quinoline, employing a method which relies on a newly developed Cu-catalyzed enantioselective alkynylation using the chiral imidazole-based biaryl P,N ligand StackPhos to establish the absolute stereochemistry. The remaining carbon atoms are then installed by means of a diastereoselective Pd-catalyzed decarboxylative allylation and the synthesis is completed after straightforward functional-group manipulation. This new synthetic method enables the most concise enantioselective synthesis of this important class of molecules to date.

A highly enantioselective copper-catalyzed alkynylation of quinolinium salts is reported. The reaction employs StackPhos, a newly developed imidazole-based chiral biaryl P,N ligand, and copper bromide to effect a three-component reaction between a quinoline, a terminal alkyne, and ethyl chloroformate. Under the reaction conditions, the desired products are delivered in high yields with ee values of up to 98 %. The transformation tolerates a wide range of functional groups with respect to both the alkyne and the quinoline starting materials and the products are easily transformed into useful synthons. Efficient, enantioselective syntheses of the tetrahydroquinoline alkaloids (+)-galipinine, (+)-angustureine, and (−)-cuspareine are reported.

Mild conditions for the gold-catalyzed dehydrative cyclization of carbamate-protected azaallylic alcohols to form saturated nitrogen heterocycles are reported. The cyclization reactions are high-yielding, operationally easy to perform, and provide heterocycles with a synthetically useful vinyl group, strategically located on the ring system, which can facilitate further transformations for target oriented synthesis. It is also demonstrated through chirality transfer experiments that the mechanism can be either cationic in nature or a Au-catalyzed addition/elimination sequence. The diverging mechanistic scenario is dependent on the nature of the substituents on the allylic alcohol and necessitates judicious substrate design.

A high-yielding stereoselective method for forming spiroketals from simple ketoallylic diols is reported. Employing catalytic [PdCl₂(MeCN)₂] in THF at 0 °C, these dehydrative cyclization reactions require only mild conditions to produce vinyl-substituted spiroketals in high yields after brief reaction times with water as the only byproduct. Using this method, the stereochemical information embedded at the nucleophile is transmitted “down-the-chain” and efficiently sets the stereochemistry at both the anomeric carbon atom and the newly formed allylic stereocenter.

The activation of allylic and propargylic alcohols for use as electrophiles represents a burgeoning new area in homogeneous gold catalysis. This review covers Au-catalyzed substitution reactions of unsaturated alcohols in which water serves as leaving group. Attention is given to different substrate classes and the mechanisms by which the reactions are believed to occur. Recent advances in chirality transfer and enantioselective reactions are also reviewed.