Asymmetric Conjugate Addition of Chiral Secondary Borylalkyl Copper Species

Abstract

We report the diastereo‐ and enantioselective conjugate addition of chiral secondary borylalkyl copper species derived from borylalkenes in situ to α,β‐unsaturated diesters. In the presence of a chiral bisphosphine‐ligated CuH catalyst, the conjugate addition provides a direct access to enantioenriched alkylboron compounds containing two contiguous carbon stereogenic centers in good yield with high diastereo‐ and enantioselectivity (up to >98:2 dr, >99:1 er) by assembling readily available starting alkenyl reagents in a single operation without using preformed organometallic reagents or chiral auxiliaries. The resulting products were used in various organic transformations. The utility of the synthetic approach was highlighted by the synthesis of (−)‐phaseolinic acid.

Copper-catalysed asymmetric reductive cross-coupling of prochiral alkenes

“…While conjugate addition of a few configurationally stable chiral alkyl metallic reagents with α-heterofunctionality as the nucleophiles 18 , 19 and 1,6-conjugate addition of allene-derived nucleophiles 20 represented successful conjugate reactions, we recently reported that catalytic alkenylboron-derived copper nucleophiles could be utilized to accomplish diastereo- and enantioselective conjugate addition of α-borylalkyl copper species (Fig. 1c ) 21 . Inspired by this work, we envisioned a non-radical strategy for asymmetric assembly of two prochiral alkenes with stereocentre formation between the two connecting carbons bearing no heteroatom substituents (Fig.…”

Restoration of catalytic activity by the preservation of ligand structure: Cu-catalysed asymmetric conjugate addition with 1,1-diborylmethane

“…As a model reaction for investigation, the underdeveloped Cu-catalysed conjugate addition with 1,1-diborylmethane to an α,β-unsaturated ketone substrate was selected. 7 …”

Cu-Catalyzed Asymmetric Alkenylation of Enone Diesters with Trialkenylboroxines

“…Beginning with the enantioenriched product 3w , a diastereoselective reduction of the keto group with sodium borohydride , and a subsequent cyclization provided lactone 4 in good yield as a 10:1 mixture of diastereomers. The anti -lactone 5 was successfully obtained via a Krapcho decarboxylation . Finally, the Ru-catalyzed oxidative cleavage of the alkenyl moiety yielded carboxylic acid 6 , which can be transformed to (+)-methylenolactocin using a literature method …”