Stereoselective Synthesis of Trisubstituted Alkenes by Nickel‐Catalyzed Benzylation and Alkene Isomerization

Abstract

Catalytic strategies that provide stereoselective access to highly substituted alkenes from abundant monosubstituted substrates are exceedingly sought-after but rare. Here, we show that a N-heterocyclic carbene-Ni I catalytic species mediates efficient union of electronically polarized terminal olefins with benzyl chlorides, in the presence of trimethylsilyl triflate and trimethylamine additives, to generate trisubstituted boron-and arene-containing trans alkenes in excellent regio-and stereoselectivities. Control experiments provide evidence for a mechanism involving branchedselective Heck-type benzylation that overrides substrate control, followed by trans-selective 1,3-hydrogen shift. The method represents a significant addition to the toolbox of reactions for the concise synthesis of unsaturated biologically active compounds.

N-Heterocyclic carbenes as privileged ligands for nickel-catalysed alkene functionalisation

“…An initial insertion of the alkene into the Ni-H bond generates an alkyl-Ni intermediate, which can react with the Scheme 8 Ni(I)/IPr-catalysed Heck-type benzylation/isomerisation for stereoselective synthesis of tri-substituted alkenes. 48 desired electrophile (via insertion or oxidative addition). Subsequent b-hydride elimination or reductive elimination affords the final product (Scheme 9b).…”

“…An extension to their previous work (Scheme 7), Koh and co-workers reported a Ni(I)/IPr catalysed branched-selective Heck-type benzylation-stereoselective olefin isomerisation methodology to access tri-substituted alkenes. 48 The same dinuclear IPr-derived Ni(I) dimeric complex (25) was used as the precatalyst, which efficiently enabled the reaction of styrenes/vinylboronates with various functionalised benzyl chlorides under basic conditions, to afford trisubstituted alkenes with high trans-selectivity. The excellent branched selectivity (where the benzyl group is attached to the more substituted olefinic carbon) of the initial Heck-type benzylation is attributed to the steric control provided by the bulky NHC ligand, which effectively overrides the olefin's strong electronic bias for linear selectivity.…”

Iron‐Catalyzed Positional and Geometrical Isomerization of Alkenes

“…[85,86,88,92] Some elegants Ni-catalyzed tandem processes incorporating a key isomerization step have also been described as a synthetically useful route towards this family of building blocks. [94,97] Never-theless, less attention has been given to this strategy using iron-based catalysts. In 2021, it was reported that structurally-defined iron(II) dichloride complexes 4-FeCl 2 and 5-FeCl 2 bearing a pincer phosphinepyridine-oxazoline or -imidazole framework were competent catalysts for the regio-and stereoselective monoisomerization of α-alkyl styrenes [144] (Scheme 10) and 1,1-disubstituted alkenyl boronates [145] (Scheme 11) respectively upon activation with NaH-BEt 3 .…”

(NHC)Ni(II)-Directed Insertions and Higher Substituted Olefin Synthesis from Simple Olefins

“…Such a technically simple and energy-efficient protocol opens a new avenue for a greener synthesis of higher substituted olefins from simple abundant terminal olefins. It saved the cost and availability problems of the alkenyl reagents in the Heck reaction and related variations (strictly speaking, that is a mechanistically different HA product synthesis method, not a standard HA). ,− This is essential in larger-scale synthesis and functionalized poly­(isobutylene) development.…”