Highly Effective Conditions for Nickel-Mediated Heck Cyclization Cascades Starting from Aryl and Vinyl Triflates

In contrast to the tremendous power of Pd-based Mizoroki–Heck reactions, methods to achieve such processes with other metals, particularly Ni, are generally lacking. Herein, we delineate specific conditions that can enable cascade variants of these C–C bond forming events to proceed smoothly under Ni catalysis. Critically, these reactions work with equal facility as their Pd-initiated counterparts when conducted intramolecularly, and in many cases are devoid of any Ni–H-mediated alkene isomerization within the starting materials and/or products as has typically been observed with previous Ni-based protocols. When conducted intermolecularly, the developed variant affords unique regioselectivity in product formation, substantively favoring 6-endo additions over the more standard 5-exo counterparts observed under Pd-based conditions. Finally, applications of the developed procedures to two different natural product syntheses are described

Ni-catalyzed Enantioselective Reductive Arylcyanation/Cyclization of N-(2-iodo-aryl) Acrylamide

A Ni/(S,S)-BDPP-catalyzed intramolecular Heck cyclization of N-(2-iodo-aryl) acrylamide with 2-methyl-2-phenylmalononitrile was developed to give oxindoles with good enantioselectivity. We found that utilizing such electrophilic cyanation reagent could tackle the deleterious...

Synthesis of (Hetero)Aryl Functionalized Azaindoline Derivatives By Palladium-Catalyzed Domino Heck Cyclization/Hiyama Cross-Coupling

A palladium-catalyzed domino Heck cyclization/Hiyama cross-coupling has been achieved for the synthesis of (hetero)aryl functionalized azaindoline derivatives bearing all-carbon quaternary centers with yields of 46-85%. The synthetic versatility of this protocol has been highlighted by the gram-scale synthesis and modification of aryl-containing complex bioactive molecules.

Domino Heck/Hiyama cross-coupling: trapping of the σ-alkylpalladium intermediate with arylsilanes

A Pd-catalyzed domino Heck cyclization/Hiyama cross-coupling sequence of aryl-tethered activated/unactivated alkenes with arylsilanes is described.

Direct photo-induced reductive Heck cyclization of indoles for the efficient preparation of polycyclic indolinyl compounds

Metal- and photocatalyst-free reductive Heck cyclization of indoles under light irradiation was developed and used to prepare polycyclic compounds and functionalize natural product analogues in moderate to good yields.