Iridium-Catalyzed Branch-Selective and Enantioselective Hydroalkenylation of α-Olefins through C–H Cleavage of Enamides

Abstract

Catalytic branch-selective hydrofunctionalization of feedstock α-olefins to form enantioenriched chiral compounds is a particularly attractive yet challenging transformation in asymmetric catalysis. Herein we report an iridium-catalyzed asymmetric hydroalkenylation of α-olefins through directed C–H cleavage of enamides. This atom-economical addition process is highly branch-selective and enantioselective, delivering trisubstituted alkenes with an allylic stereocenter. DFT calculations reveal the origin of regio- and enantioselectivity.

Chiral Trifluoromethylated Enamides: Synthesis and Applicability

“…[63][64][65] There is only one example for the synthesis of 𝛾-chiral enamides, described by the group of Li through an elegant Ir-catalyzed hydroalkenylation strategy of unactivated 𝛼-olefins promoted by a chiral ligand (Scheme 2A). 66 This method involves pre-protected substrates and the scope is limited to aliphatic alkenes. According to our previous interest, [67][68][69] we recently developed a one-pot stereoselective isomerization method of 𝛼-chiral allylic amines catalyzed by 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as a simple organocatalyst followed by a diastereoselective reduction of the imine-tautomer with DIBAL-H to obtain 𝛼, 𝛾-chiral aliphatic amines (Scheme 2B).…”

“…Various substituents at the R 1 -position on the 𝛼-chiral allylic amine (C𝛼) could be tolerated including trifluoromethyl-(2b), bromide-(2c) and m-methoxy-groups (2d). The bulky naphthyl-substituent (2e) A) Ir-catalyzed enantioselective hydroalkenylation of α-olefins (Li) [66] C) This work . .…”

Ir-Catalyzed Distal Branch-Selective Hydroarylation of Unactivated Internal Alkenes with Benzanilides via C–H Activation along with Consecutive Isomerization

“…However, the cationic iridium-catalyzed addition of C–H to alkenes heavily depends on the nature of the double bond. This is mainly limited to the reaction of terminal alkenes, − strained alkenes, conjugated alkenes, and functionalized alkenes . According to our survey, internal alkenes, such as β-substituted styrenes and internal aliphatic alkenes, have rarely been used in iridium-catalyzed C–H alkylation.…”

“…On the other hand, Dong’s group exhibited the use of a transient directing group to achieve branch-selective addition starting from simple ketones . Recently, Li et al also reported an enantioselective and branch-selective addition of a vinylic C–H bond to terminal alkenes . However, the cationic iridium-catalyzed addition of C–H to alkenes heavily depends on the nature of the double bond.…”

“…While previous reports have stated that the choice of ligand greatly determined the regioselectivity of the product, ,, we focused on optimization of the ligand to improve the branch-to-linear (B/L) ratio (Table ). When the biaryl bisphosphine ligand L1 , L2 , or L3 was used, the B/L ratio was around 3/1 to 5/1 (Table , Entry 3 and Table , Entries 1 and 2).…”