Open AccessEnantioselective C(sp3)–C(sp3) cross-coupling of non-activated alkyl electrophiles via nickel hydride catalysis
Author(s) -
Srikrishna Bera,
Runze Mao,
Xile Hu
Publication year - 2020
Publication title -
nature chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.996
H-Index - 232
eISSN - 1755-4349
pISSN - 1755-4330
DOI - 10.1038/s41557-020-00576-z
Subject(s) - chemistry , alkyl , enantioselective synthesis , electrophile , hydride , nucleophile , combinatorial chemistry , nickel , organic chemistry , catalysis , metal
Cross-coupling of two alkyl fragments is an efficient method to produce organic molecules rich in sp 3 -hybridized carbon centres, which are attractive candidate compounds in drug discovery. Enantioselective C(sp 3 )-C(sp 3 ) coupling is challenging, especially of alkyl electrophiles without an activating group (aryl, vinyl, carbonyl). Here, we report a strategy based on nickel hydride addition to internal olefins followed by nickel-catalysed alkyl-alkyl coupling. This strategy enables the enantioselective cross-coupling of non-activated alkyl halides with alkenyl boronates to produce chiral alkyl boronates. Employing readily available and stable olefins as pro-chiral nucleophiles, the coupling proceeds under mild conditions and exhibits broad scope and high functional-group tolerance. Applications for the functionalization of natural products and drug molecules, as well as the synthesis of chiral building blocks and a key intermediate to (S)-(+)-pregabalin, are demonstrated.