Pd^II‐Catalyzed C(alkenyl)−H Activation Facilitated by a Transient Directing Group**

Abstract

Palladium(II)-catalyzed C(alkenyl)À H alkenylation enabled by a transient directing group (TDG) strategy is described. The dual catalytic process takes advantage of reversible condensation between an alkenyl aldehyde substrate and an amino acid TDG to facilitate coordination of the metal catalyst and subsequent C(alkenyl)À H activation by a tailored carboxylate base. The resulting palladacycle then engages an acceptor alkene, furnishing a 1,3-diene with high regio-and E/Z-selectivity. The reaction enables the synthesis of enantioenriched atropoisomeric 2-aryl-substituted 1,3dienes, which have seldom been examined in previous literature. Catalytically relevant alkenyl palladacycles were synthesized and characterized by X-ray crystallography, and the energy profiles of the C(alkenyl)À H activation step and the stereoinduction model were elucidated by density functional theory (DFT) calculations.

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

“…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. Notably, unbiased aliphatic alkenes were found to be viable substrates for this transformation, albeit with diminished efficiency.…”

Enantioselective Hydroalkenylation and Hydroalkynylation of Alkenes Enabled by a Transient Directing Group

“…A limitation is that the other type of trisubstituted alkene (α,b,btrisubstituted), gave only the corresponding Heck byproduct (see mechanistic discussion below). Importantly, we were able to expand the alkenyl aldehyde scope beyond orthoalkenylbenzaldehydes to a conjugated dienyl aldehyde (3ka) and non-conjugated aldehyde containing purely aliphatic tether (3la), [26] both of which have not been demonstrated previously in TDG/Pd-catalyzed Heck-type alkene functionalizations. Enantioselectivity was high in both cases (96:4 er), while yields were 57% and 24%, respectively.…”

Functionality‐Directed Regio‐ and Enantio‐Selective Olefinic C−H Functionalization of Aryl Alkenes

“…Two olefinic palladacycle complexes were successfully obtained by simply combining benzaldehyde, Pd(OAc) 2 and a TDG in pyridine, which was used for mechanistic elucidation with the combination of DFT calculations. [33] This TDG strategy was also successfully applied to enantioselective olefin di-functionalization of alkenyl benzaldehydes by the same research group. [34] Nearly at same time, our group reported a palladiumcatalyzed enantio-selective α-CÀ H alkenylation of aryl alkenes to prepare axially chiral aryl 1,3-dienes 30, which was performed using 15 mol% Pd(OAc) 2 , 30 mol% L-tert-leucine as a transient directing group, equivalent of MnO 2 and BQ as Scheme 27. α-CÀ H alkenylation of plain 2-vinyl benzylamides (Zhang and Zhong, 2022).…”

“…In recent years, remarkable advances have been made in chelation-assisted alkenyl CÀ H functionalization of the aryl alkenes bearing an ortho-directing group. [30][31][32][33][34] Herein, we afforded an over-Yuhang Zhu was born in Zhejiang, China. (1999)(2000)(2001)(2002)(2003)(2004), a professor at Fudan University in Shanghai (2005Shanghai ( -2006 and at Hangzhou Normal University (2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019)(2020)(2021)(2022), and an associate professor at Nanyang Technological University in Singapore (2006Singapore ( -2011.…”