Asymmetric cross-coupling of alkyl, alkenyl and (hetero)aryl nucleophiles with racemic allyl halides

Abstract

Single enantiomer molecules are important for the pharmaceutical and agrochemical industries and increasingly so in materials science. Most strategies to obtain enantiomerically enriched molecules rely on either generating new stereogenic centres from prochiral substrates or resolving racemic mixtures of enantiomers. Dynamic asymmetric processes are powerful methods that use racemic mixtures of chiral substrates as starting material. This Feature Article focuses on asymmetric additions to racemic substrates using non-stabilized sp- and sp-hybridized nucleophiles. These reactions bear considerable resemblance to traditional sp-sp cross-coupling reactions in terms of the starting materials used and the products obtained, but the reaction mechanisms are necessarily different.

Guanidine–Copper Complex Catalyzed Allylic Borylation for the Enantioconvergent Synthesis of Tertiary Cyclic Allylboronates

“…[2h] In copper-catalyzed asymmetric allylic borylation, it is often observed that rather than am etal-allyl complex, ac opper-boryl intermediate is first formed followed by stereoselective S N 2' attack. [13] Only recently Ito and co-workers developed ad irect enantioconvergent transformation (DECT) where the two enantiomers of the allylic ethers underwent anti-orsyn-S N 2' substitution, respectively,leading to the same borylated product. [13] Only recently Ito and co-workers developed ad irect enantioconvergent transformation (DECT) where the two enantiomers of the allylic ethers underwent anti-orsyn-S N 2' substitution, respectively,leading to the same borylated product.…”

“…[2h,4] Racemic allylic substrates, though easy to obtain, are challenging to be used in stereo-convergent borylation. [13] Only recently Ito and co-workers developed ad irect enantioconvergent transformation (DECT) where the two enantiomers of the allylic ethers underwent anti-orsyn-S N 2' substitution, respectively,leading to the same borylated product. [4d] Over the past decade,w eh ave developed asymmetric transformations by using chiral guanidines as Brønsted base catalysts,aswell as guanidinium salts as phase-transfer or ionpair catalysts.…”

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

“…Organozirconium compounds are another class of organometallic reagents that have been used widely in the synthesis of complex molecules. Recently, Fletcher and co-workers demonstrated the applicability of a hydrozirconation in the ACA reaction to non-heterocyclic conjugated substrates [22][23][24][25][26], while the Šebesta group was the first to report the copper-catalysed addition of organozirconium reagents to N-substituted 2,3dehydro-4-piperidones (Scheme 4A) [27]. In the latter work, the organozirconium reagents were generated first in situ by the hydrozirconation of alkenes.…”

Enantio‐ and Diastereoselective Suzuki–Miyaura Coupling with Racemic Bicycles

“…Asymmetric methods that generate highly enantioenriched chiral molecules from racemic substrates are inherently attractive as there are theoretically more chiral than prochiral molecules . While kinetic resolutions (KRs) are well explored, these procedures suffer from the intrinsic drawback of yields lower than 50 % .…”