Stereodivergent Synthesis of BothZ- andE-Alkenes by Photoinduced, Ni-Catalyzed Enantioselective C(sp³)–H Alkenylation

Abstract

The enantio- and stereoselective synthesis of stereodefined alkenes, especially the functionalized Z-isomer with an allylic stereogenic center, remains a great challenge. We herein report an enantioselective benzylic C­(sp3)–H alkenylation of simple alkylarenes with vinyl bromides via photoinduced nickel catalysis, which allows for the stereodivergent synthesis of both enantioenriched Z- and E-alkenes bearing aryl-substituted, allylic tertiary stereogenic centers. Interestingly, the tunable Z/E-selectivity is achieved by energy transfer catalysis via a judicious choice of the photocatalyst counteranion. This versatile strategy features simple starting materials, mild reaction conditions, broad substrate scope, divergent Z- and E-selectivity, and high enantioselectivities. Moreover, a formal asymmetric benzylic C­(sp3)–H alkylation can also be achieved via a one-pot alkenylation/reduction sequence, providing a complementary strategy to address the notoriously challenging stereochemical control in C­(sp3)–C­(sp3) bond construction.

E/Z Photoisomerization of Olefins as an Emergent Strategy for the Control of Stereodivergence in Catalysis

“…This example exploits an interesting feature exerted by photocatalysts with different anions. In this case, the use of the ([Ir{dFCF 3 ppy} 2 (dtbbpy)]PF6, E T =60.1 kcal ⋅ mol −1 ) [43] rendered the Z ‐isomer, while the chloride analog did not promote the isomerization. This differential behavior was explained in terms of the potential counter anion effect studied by Yoon and Meyer, respectively, who described that a more‐coordinating anion can reduce the lifetime of the triplet excited species which is responsible for the photoisomerization step [44] .…”

“…More recently Huo and collaborators have described an interesting approach that enables the alkenylation of benzylic positions by merging Ni and Ir catalysis (Scheme 11). [43] The postulated mechanism involves a first oxidative addition of the alkenyl bromide to the catalytically active Ni(0) species 127 . The newly formed Ni(II) species 128 captures the in situ generated benzylic radical 129 from bromine‐radical‐mediated C−H cleavage.…”

Switchable Divergent Synthesis Using Photocatalysis

“…In 2021, a stereodivergent enantioselective C­(sp 3 )–H alkenylation reaction using a photocatalyst and Ni catalyst was reported by Huo (Scheme ). The reaction selectively affords E isomer 5 -( E )- 3 and Z isomer 5 -( Z )- 3 from ( E )-2-bromovinylbenzene ( 5 - 1 ) and 4-ethylbiphenyl ( 5 - 2 ) by changing the counteranion in the photocatalyst . The reactions of 5 - 1 and 5 - 2 were initiated by the oxidative addition of vinyl bromide 5 - 1 with Ni 0 catalyst 5 - A to furnish Ni II species 5 - B .…”

Synthetic Applications of Photocatalyzed Halogen‐Radical Mediated Hydrogen Atom Transfer for C−H Bond Functionalization

“…The Huo group gave an important contribution to the field of photoredox-generated halogen radicals for HAT by reporting several enantioselective transformations based on bromine radicals. [98][99][100][101] In one of these examples, the enantioselective acylation of α-to-N C(sp 3 )À H bonds using ubiquitous carboxylic acids as acylating partner to produce α-amino ketones was reported (Scheme 19). [98] In detail, when an isopropyl acetate solution of acetic acid (19.1, 0.1 mmol) and N-pentyl benzamide (19.2, 3.0 equiv.)…”