Ni-Catalyzed Regioselective 1,2-Dialkylation of Alkenes Enabled by the Formation of Two C(sp³)–C(sp³) Bonds

Abstract

We disclose a Ni-catalyzed vicinal difunctionalization of alkenes with benzyl halides and alkylzinc reagents, which produces products with two new alkyl–alkyl bonds. This alkene dialkylation is effective in combining secondary benzyl halides and secondary alkylzinc reagents with internal alkenes, which furnishes products with three contiguous all-carbon secondary stereocenters. The products can be readily elaborated to access complex tetralene, benzosuberene, and bicyclodecene cores. The reaction also features as the most efficient alkene difunctionalization process to date with catalyst loadings down to 500 ppm and the catalytic turnover number (TON) and turnover frequency (TOF) registering up to 2 × 103 and 165 h–1 at rt, respectively.

Role of the X Coligands in Cyclometalated [Ni(Phbpy)X] Complexes (HPhbpy = 6-Phenyl-2,2′-bipyridine)

“…We tentatively ascribe the huge difference in terms of selectivity for reaction I vs reaction II to the possibility for Zn to form a chelate binding using the dioxane function in reaction II, thus tuning its reactivity. Similar phenomena have been reported previously. − Further, the role of the different halides might go beyond that of being a more or less suitable leaving group. Salt byproducts are known to play a critical role in Negishi cross-coupling reactions. , …”

Palladium-Catalyzed γ,γ′-Diarylation of Free Alkenyl Amines

“…Alkenes are important feedstocks in synthetic chemistry due to their versatility; they are inherently nucleophilic but can easily be made electrophilic by the addition of certain functional groups or catalysts. − Alkenes can also serve as activating groups for adjacent C–H bonds, allowing even greater synthetic utility. − One of the biggest challenges for alkene functionalization is to achieve regioselectivity. − While this is easily overcome for terminal olefins − and cyclization reactions, , internal alkenes often undergo poor regiochemically selective reactions without the aid of activating functional groups. This has spawned a significant research enterprise exploring how to achieve regioselective transformations in electronically unbiased alkenes. − For transition metal-catalyzed reactions, one of the most effective strategies has been the use of directing groups (DGs). A directing group can be thought of as an auxiliary ligand on the substrate that coordinates to the metal, thereby driving the regioselectivity through the formation of the most accessible cyclometalated intermediate.…”

Directed Nickel-Catalyzed Diastereoselective Reductive Difunctionalization of Alkenyl Amines

“…Transition-metal-catalyzed dicarbofunctionalization of alkenes is an emerging protocol developed to provide expeditious and economical access to molecular complexity from abundant and readily available materials . While significant progress has been made in recent years, most alkene multicomponent dicarbofunctionalizations are still limited to activated alkene substrates or Csp- or Csp 2 -hybridized coupling partners for diarylation, arylvinylation, arylalkynlation, and similar reactions . Reactions involving the regioselective introduction of Csp 3 -hybridized carbogenic groups present a formidable challenge because of their attenuated reactivity and high tendency toward β-hydride elimination.…”