Nickel-Catalyzed Asymmetric Reductive Arylbenzylation of Unactivated Alkenes

Abstract

Reported is an asymmetric reductive dicarbofunctionalization of unactivated alkenes.U nder the catalysis of aN i/BOXs ystem, various aryl bromides,i ncorporating ap endant olefinic unit, were successfully reacted with an arrayo fp rimary alkylb romides in the presence of Zn as ar eductant, furnishing as eries of benzene-fused cyclic compounds bearing aquaternary stereocenter in high enantioselectivities.N otably,t his reaction avoids the use of pregenerated organometallics and demonstrates high tolerance of sensitive functionalities.T he preliminary mechanistic investigations reveal that this Ni-catalyzed reaction proceeds as acascade consisting of migratory insertion and cross-coupling with an ickel(I)-mediated intramolecular 5-exo cyclization as the enantiodetermining step.Asymmetric difunctionalizations of unactivated alkenes are among the most important reactions in organic synthesis,a s diverse optically active compounds can be accessed in asingle step using simple olefins as precursors.T ransition-metal catalysis has proven to be ap owerful tool for dicarbofunctionalizations of unactivated alkenes including diarylation, dialkylation as well as arylalkylation, and tremendous advances have been achieved recently using both redox-neutral [1][2][3] and reductive strategies. [4] However,a symmetric versions of these reactions are still rare.I nt he field of diarylation, Sigman et al. developed aP d-catalyzed enantioselective diphenylation of 1,3-dienes, [3c] while Brown and his coworker reported aC u-promoted asymmetric diarylation of pendant olefins tethered on aryl boronates. [2d] Recently,L iu et al. achieved Cu-catalyzed enantioselective dicarbofuntionalizations of styrenes involving the installation of aC F 3 moeity. [3d,j] Furthermore,F ue tal. accomplished an enantioselective variant of the two-component arylalkylation. [2b] In this Ni-catalyzed reaction, arylboranes incorporating aterminal olefinic unit were reacted with unactivated alkyl halides, affording various benzofurans and indanes in high enantioselectivities (Scheme 1A). However,a ll the aforementioned asymmetric dicarbofunctionalizations of unactivated olefins require the use of pregenerated organometallics as coupling partners,and is less desirable from the viewpoint of both stepeconomy and functionality tolerance.On the contrary,t he reductive strategy of dicarbofunctionalizations of C À Cd ouble bonds allows the incorporation of two carbo moieties directly from either aryl or alkyl halides with the assistance of ar educing agent, and thus eliminates the additional step of preparation of sensitive organometallics,a sw ell as the related issue of functional-group compatibility.D espite rapid progresses in this area, the asymmetric version of reductive dicarbofunctionalization of unactivated olefins still remains elusive. [5,6] Very recently,o ur group reported ar acemic version of Ni-catalyzed reductive arylalkylation of unactivated alkenes tethered to aryl bromides. [4i] In this context, we report asignificant advance of our method as w...

Nickel‐CatalyzedDicarbofunctionalization of Alkenes†

“…Based on these works, recently, the reaction was extended to benzyl chlorides by the same group (Scheme 69). [ 141 ]…”

Nickel-Catalyzed Reductive Asymmetric Aryl-Acylation and Aryl-Carbamoylation of Unactivated Alkenes

“…In contrast, the reactions employing the PyBOX L9 or PHOX L10 as a ligand failed to deliver compound 3aa (entries 9 and 10). Next, several Ni(II) salts and Ni(COD) 2 were surveyed (entries [11][12][13][14], and the highest enantioselectivity was achieved in the case of NiBr 2 •diglyme (entry 14). In this case, the yield was also increased to 38%.…”

“…[1][2][3][4][5][6] The majority of these reactions relies on a facially selective Heck-type arylmetallation of the pendant olefinic unit as the enantiodetermining step, 7 which is followed by trapping of the generated σ-alkylmetal species with either a nucleophile or an electrophile. Based on this strategy, asymmetric aryl-alkylation, [8][9][10] diarylation, [10][11][12][13] arylbenzylation, 14 aryl-alkenylation 15,16 and aryl-alkynylation 13,17,18 of incorporated alkenes have been developed under palladium, copper or nickel catalysis.…”

Enantioselective Intermolecular Heck and Reductive Heck Reactions of Aryl Triflates, Mesylates, and Tosylates Catalyzed by Nickel

“…[7] Notably, recent years also witnessed a surge of interest in Ni-catalyzed asymmetric bifunctionalization of alkenes with two different organohalides or sulfonates. [8] Herein, we disclose our finding on first examples of asymmetric intermolecular Heck reaction using nickel catalysts. Cheap aryl mesylates and tosylates, which are readily prepared from phenols, coupled efficiently, as well as more reactive aryl triflates.…”