Enantioselective Synthesis of All‐Carbon Quaternary Stereogenic Centers via Copper‐Catalyzed Asymmetric Allylic Alkylation of (Z)‐Allyl Bromides with Organolithium Reagents

Abstract

A copper/phosphoramidite catalyzed asymmetric allylic alkylation of Z trisubstituted allyl bromides with organolithium reagents is reported. The reaction affords all-carbon quaternary stereogenic centers in high yields and very good regio- and enantioselectivity. This systematic study illustrates the crucial role of the olefin geometry of the allyl substrate on the outcome of the reaction and provides a viable alternative to access these important structural motifs.

Biocatalytic Redox Reactions with Allylic Alcohols

“…Although it was not possible to obtain a pure fraction of (Z)-3 with the procedure described previously. A new method was found to synthesize after three steps with 70% yield 3 . The next step is performing the biocatalysis of (Z)-3, with C. albicans and evaluate the difference on the products stereochemistry compared to (E)-3.…”

Cu-catalyzed enantioselective allylic alkylation with organolithium reagents

“…1b) [10][11][12] , Cu-catalyzed AAA typically represents the most efficient catalytic process for the use of organometallic reagents, including organoaluminium, organozinc, organomagnesium, and organozirconium compounds. However, the use of cheap and readily available organolithium reagents had not been successfully applied in catalytic asymmetric C-C bond formation until recently [13][14][15][16][17][18] . This protocol describes the application of organolithium compounds for the catalytic enantioselective C-C bond formation of tertiary and quaternary stereogenic centers.…”

“…As part of this method development, we studied the influence of the E or Z geometry of the prochiral trisubstituted allylic substrate on the stereochemical outcome of the copper-catalyzed AAA (Fig. 2e) 16 . In some cases, the reaction of (Z)-allyl bromides affords higher selectivity than that obtained using (E)-allyl bromides, therefore providing an alternative for the synthesis of all-carbon quaternary centers.…”

Catalytic Asymmetric Construction of the Tryptanthrin Skeleton via an Enantioselective Decarboxylative [4 + 2] Cyclization

“…The first one is controlling the chemoselectivity of the reaction because the carbonyl group (CO) of isatins in most cases exhibits high reactivity which, in principle, can undergo a decarboxylative [4 + 2] cyclization with vinyl benzoxazinanones 1 to generate the byproducts 4 . The second challenge is controlling the branch/linear selectivity in the allylic amination step; − otherwise, byproducts 5 from ring opening would be generated. The final challenge is controlling the enantioselectivity of the reaction.…”