Ligand‐Controlled NiH‐Catalyzed Regiodivergent Chain‐Walking Hydroalkylation of Alkenes

Abstract

A NiH-catalyzed migratory hydroalkylation of alkenyl amines with predictable and switchable regioselectivity is reported. By utilizing a ligand-controlled, directing group-assisted strategy, various alkyl units are site-selectively installed at inert sp 3 CÀ H sites far away from the original C=C bonds. A range of structurally diverse α-and β-branched protected amines are conveniently synthesized via stabilization of 5-and 6-membered nickelacycles respectively. This method exhibits broad scope and high functional group tolerance, and can be applied to late-stage modification of medicinally relevant molecules.

Remote arylalkylation of unactivated alkenesvia6- or 7-membered nickelacycles with excellent diastereofidelity

“…The trans orientation of the stereocenters generated from arylalkylation of αor β-substituted substrates arises from the formation of the more stable trans-nickelacycle upon C-C bond reductive elimination in analogy to our previous work (also see the following DFT calculation). 13,17 A more sterically hindered dimethyl group at the β position led to a low yield (2an). Importantly, challenging internal alkenes successfully engaged in the reaction to afford only the syn-isomeric products (2ap-2ax).…”

Redox-neutral remote amidation of alkenyl alcoholsvialong-range isomerization/transformation

“…In this area, transition metal-catalyzed alkene isomerization by “chain-walking” in combination with a sequential chemical transformation could realize remote functionalization, which can effectively reduce the number of manipulated steps and functional group protection/deprotection processes, and has received extensive attention and exploration. 2 As a result, molecular complexity can be achieved in a rapidly increased fashion from readily available starting materials through a thermodynamically favorable process.…”

Remote Stereocenter through Amide-Directed, Rhodium-Catalyzed Enantioselective Hydroboration of Unactivated Internal Alkenes

“…First, metal-catalyzed enantioselective hydroboration of unactivated trisubstituted alkene is particularly limited due to the low reactivity. − Diastereoselective processes are even less common. , Second, the catalyst must exert precise regio- and enantiocontrols even within a conformationally flexible, six-membered metallacycle . Third, isomerization of the allyl amide to an enamide should be avoided, as this could lead to decreased regio-, diastereo-, and enantioselectivities due to the presence of an enamide hydroboration product.…”