A Bulky Chiral N‐Heterocyclic Carbene Nickel Catalyst Enables Enantioselective C−H Functionalizations of Indoles and Pyrroles

Abstract

An enantioselective nickel(0)-catalyzedC À Hf unctionalization of indoles and pyrroles that does not require the typical Lewis basic directing groups is disclosed. The reaction provides access to valuable tetrahydropyridoindoles and tetrahydroindolizines in high yields and enantioselectivity under mild reaction conditions.T he process is characterized by aclear endo-cyclization preference to yield the sought-after six-membered-ring products.K ey for the success of the activation and selectivity in the cyclization was the development of anovel chiral SIPr carbene ligand analogue with very bulky flanking groups.

Nickel/Brønsted Acid-Catalyzed Chemo- and Enantioselective Intermolecular Hydroamination of Conjugated Dienes

“…In recent years, research toward nickel-catalyzed oxidative addition with X-H (X = C, O …) bonds has become a hot theme owing to earth-abundance of nickel and its great potential in oxidative addition (Ananikov, 2015, Tasker et al., 2014, Wang, 2016; Figure 1C). Significant progress has been made in the asymmetric hydrofunctionalization of alkenes through nickel-catalyzed reactions (Bezzenine-Lafollee et al., 2017, Cai et al., 2019, Chen and Lu, 2018, Cheng et al., 2018, Cheng et al., 2019, Diesel et al., 2018, Diesel et al., 2019, Donets and Cramer, 2013, Li et al., 2018, Li et al., 2019a, Lv et al., 2018, Richmond and Moran, 2018, Woźniak and Cramer, 2019, Xiao et al., 2016, Xiao et al., 2018, Zhang et al., 2019). Chiral centers are generally induced via a carbon-carbon bond-forming process, involving the direct oxidative addition of C-H bonds (Cai et al., 2019, Cheng et al., 2018, Cheng et al., 2019, Diesel et al., 2018, Diesel et al., 2019, Donets and Cramer, 2013, Li et al., 2019a, Lv et al., 2018, Woźniak and Cramer, 2019, Zhang et al., 2019) or an external stoichiometric reductant, such as alcohol (Chen et al., 2019) or hydrosiloxane (Ahlin and Cramer, 2016).…”

Nickel-Catalyzed Regio- and Enantioselective Hydroarylation of 1,3-Dienes with Indoles

“…[22][23][24] The development of methods for the synthesis of chiral indole derivatives is an important task in organic synthesis. 13,[25][26][27][28][29][30][31] As part of our ongoing research aimed at developing nickel-catalyzed C-C bond-forming reactions 15,19,[32][33][34][35][36] , we herein report a method for nickel-catalyzed asymmetric hydroarylation of aliphatic dienes with indoles to afford chiral indole derivatives with high regio-and enantioselectivities (Scheme 1C).…”

Enantioselective Three‐Component Coupling of Heteroarenes, Cycloalkenes and Propargylic Acetates

“…In another type of reaction pathway, low-valent late transition metals (Ni, [5] Rh [6] and Ir [7] ) were reported to cleave heteroaryl C À H bonds and then promote asymmetric b-insertion to pendant alkenes. [8] The intermolecular insertion of this type, however, is also challenging and such examples are limited.…”