Construction of axial chirality by asymmetric alpha C–H alkenylation of aryl alkenes

Abstract

An asymmetric α-C–H alkenylation of aryl alkenes has been disclosed to provide axially chiral aryl 1,3-dienes, proceeding through six-membered exo-cyclopalladation, assisted by an aldehyde/l-t-leucine derived transient chiral auxiliary.

Recent Advances in Alkenyl sp2 C–H and C–F Bond Functionalizations: Scope, Mechanism, and Applications

“…However, electronically activated alkenes such as vinyl ketones, vinyl sulfones, and acrylamides were proven to be incompatible with the conditions. Unlike this asymmetric coupling reactions where endo metallacycles were generated to regioselectively functionalize the vinylic β-C­(sp 2 )–H bonds of styrene derivatives, the same group expanded to establish the asymmetric α-C­(sp 2 )–H alkenylations of styrenes using l - t -leucine as the transient chiral auxiliary through a six-membered exo -cyclopalladation process (Scheme b) …”

“…Unlike this asymmetric coupling reactions where endo metallacycles were generated to regioselectively functionalize the vinylic β-C(sp 2 )−H bonds of styrene derivatives, the same group expanded to establish the asymmetric α-C(sp 2 )−H alkenylations of styrenes using L-t-leucine as the transient chiral auxiliary through a six-membered exo-cyclopalladation process (Scheme 22b). 69 Almost simultaneously, Engle and co-workers also reported their exploration of a TDG approach to realize the feasibility of palladium(II)-catalyzed α-C−H olefination of styrenes by the generation of an exo alkenyl palladacycle, providing access to diverse 2-aryl-substituted 1,3-dienes with high regio-and E/Zselectivity (Scheme 23). 70 In this report, commercially available tert-leucine was identified as the optimal transient directing group, and alkenyl aldehydes with different substitution patterns could be readily olefinated to the expected coupling products.…”

Transition metal-catalyzed double Cvinyl–H bond activation: synthesis of conjugated dienes

“…Recently, Zhang and co-workers also reported the synthesis of chiral aryl 1,3-dienes 184 by a Pd( ii )-catalyzed coupling reaction between 2-vinyl benzaldehydes 182 and electron-deficient alkenes 183 , which proceeded through a 6-membered exo -palladacycle mechanism (Scheme 81). 113 They utilized an aldehyde/ l - t -leucine derived transient chiral auxiliary as the directing group for the α-C–H alkenylation reaction. Both substrates 182 and 183 bearing different functional groups were well tolerated and furnished the desired products 184 in good yields with high enantioselectivity (up to 99% ee).…”

Cross-Coupling Reactions between Alkenes by C–H Cyclometalation

“…Template for SYNLETT Thieme environmentally benign cobalt catalysis 20 and cross-coupling by exo-cyclopalladation. 24,27,32,37 as well as tandem cyclization. 58 In this Account, we would like to summarize transition-metalcatalyzed cross-coupling reactions between alkenes to generate 1,3-dienes by C−H alkenylation, 1,4-dienes by C−H allylation, [38][39][40][41][42][43][44][45] multi-substituted alkenes by hydroalkenylation, [46][47][48][49][50][51] and heterocycles by tandem alkenyl C-H functionalization and annulation.…”

“…[52][53][54][55][56][57][58][59][60][61] Asymmetric alkenyl C−H alkenylation to prepare axially chiral aryl 1,3-dienes was also discussed. [26][27][28]36,37 2 Alkenyl C-H Alkenylation Alkenyl C−H alkenylation represents the most studied reactions in cross-coupling between alkenes, providing valuable 1,3-dienes in E/Z selectivity. The cross-coupling starts with the olefinic C−H activation to form five-or six-membered endometallocycle I and exo-metallocycle II, and the subsequent olefin coordination and insertion affords larger sized metallocycle III and IV, which produces 1,3-dienes 1 and 2 by β-H elimination.…”