Recent advances in allylation of chiral secondary alkylcopper species

Abstract

The transition-metal-catalyzed asymmetric allylic substitution represents a pivotal methodology in organic synthesis, providing remarkable versatility for complex molecule construction. Particularly, the generation and utilization of chiral secondary alkylcopper species have received considerable attention due to their unique properties in stereoselective allylic substitution. This review highlights recent advances in copper-catalyzed asymmetric allylic substitution reactions with chiral secondary alkylcopper species, encompassing several key strategies for their generation: stereospecific transmetalation of organolithium and organoboron compounds, copper hydride catalysis, and enantiotopic-group-selective transformations of 1,1-diborylalkanes. Detailed mechanistic insights into stereochemical control and current challenges in this field are also discussed.

Keywords: allylic substitution; chiral secondary organocopper; copper-mediated reaction; stereoselectivity.

Scheme 1

Representative transition-metal catalysis for allylic substitution.

Scheme 2

Formation of stereogenic centers in copper-catalyzed allylic alkylation reactions.

Scheme 3

Copper-mediated, stereospecific S_N2-selective allylic substitution through retentive transmetalation sequence.

Scheme 4

ZnCl₂-promoted stereospecific S_N2' allylic substitution of secondary alkylcopper species via sequential iodide–lithium–copper transmetalation.

Scheme 5

Temperature and time-dependent configurational stability of chiral secondary organocopper species.

Scheme 6

DFT analysis of B–C bond lengths in various boronate complexes and correlation with reactivity.

Scheme 7

Copper-catalyzed stereospecific allylic alkylation of secondary alkylboronic esters via tert-butyllithium activation.

Scheme 8

Copper-catalyzed stereospecific allylic alkylation of chiral tertiary alkylboronic esters via adamantyllithium activation.

Scheme 9

DFT-calculated energy surface for boron-to-copper transmetalation of either the tert-butyl group or the adamantyl group.

Scheme 10

CuH-catalyzed enantioselective allylic substitution and postulated catalytic cycle.

Scheme 11

CuH-catalyzed enantioselective allylic substitution of vinylarenes.

Scheme 12

CuH-catalyzed stereoselective allylic substitution of vinylboronic esters.

Scheme 13

(a) Generation of chiral copper species via enantioselective CuH addition to vinylBpin. (b) Regarding the origin of diastereoselectivity in CuH-catalyzed enantioselective allylic substitution.

Scheme 14

CuH-catalyzed enantioselective allylic substitution of 1‐trifluoromethylalkenes with 18-crown-6.

Scheme 15

CuH-catalyzed enantioselective allylic substitution of terminal alkynes.

Scheme 16

Copper-catalyzed enantiotopic-group-selective allylic substitution of 1,1-diborylalkanes.

Scheme 17

(a) Computational and (b) experimental studies to elucidate the mechanistic details of the enantiotopic-group-selective transmetalation.

Scheme 18

Copper-catalyzed regio-, diastereo- and enantioselective allylic substitution of 1,1-diborylalkanes.

Scheme 19

(a) Experimental and (b) computational studies to understand the stereoselectivities in oxidative addition step.