Copper(I)‐Catalyzed Asymmetric Conjugate 1,6‐, 1,8‐, and 1,10‐Borylation

Abstract

Catalytic asymmetric remote conjugate borylation is challenging as the control of regioselectivity is not trivial, the electrophilicity of remote sites is extenuated, and the remote asymmetric induction away from the carbonyl group is difficult. Herein, catalytic asymmetric conjugate 1,6‐, 1,8‐ and 1,10‐borylation was developed with excellent regioselectivity, which delivered α‐chiral boronates in moderate to high yields with high enantioselectivity. The produced chiral boronate smoothly underwent oxidation, cross‐coupling, and one‐carbon homologation to give synthetically versatile chiral compounds in moderate yields with excellent stereoretention. Furthermore, a stereomechanistic analysis was conducted using DFT calculations, which provides insights into the origins of the regioselectivity. Finally, the present 1,6‐borylation was successfully applied in an efficient one‐pot asymmetric synthesis of (−)‐7,8‐dihydrokavain.

First-Row d-Block Element-Catalyzed Carbon–Boron Bond Formation and Related Processes

“…β-Borylation of α,β-unsaturated carbonyl and related compounds continues to be an active area of research (Scheme a). , Ferrocenyl-type ligands such as Josiphos and Taniaphos are particularly efficient for controlling the enantioselectivity of these transformations (Scheme b). ,, For example, Whiting and co-workers expanded on their previous work and demonstrated ligand-controlled sequential asymmetric protoborations leading to syn - or anti -diboryl esters to access chiral syn - and anti -1,3-diol derivatives (Scheme c) wherein Josiphos ligands enabled the effect of the existing chiral center to be overridden. Likewise, catalytic asymmetric conjugate 1,6-, 1,8-, and 1,10-borylations using Josiphos ligands afford α-chiral boronates with high enantioselectivity . The β-borylation of α,β-unsaturated carbonyl compounds followed by oxidation and subsequent cyclization affords a benzoxazinone scaffold .…”

“…Likewise, catalytic asymmetric conjugate 1,6-, 1,8-, and 1,10borylations using Josiphos ligands afford α-chiral boronates with high enantioselectivity. 544 The β-borylation of α,βunsaturated carbonyl compounds followed by oxidation and subsequent cyclization affords a benzoxazinone scaffold. 545 Recyclable copper nanoparticles (nanoferrite-supported Cu nanoparticles) are also effective as a catalyst for the borylation of α,β-unsaturated carbonyl compounds.…”

Ruthenium(ii)-catalyzed regioselective 1,6-conjugate addition of umpolung aldehydes as carbanion equivalents

“…47 The utility of the reaction was further examined on linear and cyclic aliphatic aldehydes with increased base loading, generating the desired products 34-35 in lower yields. For the conjugated electrophile, both electron-withdrawing and donating groups on the aryl ketone provided the desired 1,6addition products in moderate to good yields (36)(37)(38)(39)(40)(41)(42)(43). The thiophene-derived heteroarene ketone also led to a moderate yield (44).…”

“…34,35 Expansion of metal-catalyzed 1,6-additions to boryl and silyl groups are represented by the works of Lam, 36,37 Liao 38 and Newhouse. 39 While these advancements are very signicant, most involve stoichiometric use of organometallic nucleophiles, which inevitably leads to sizable metallic waste and poor atom economy. With our group's continuous pursuit in the umpolung of hydrazones as "so" alkyl carbanions (Fig.…”

Umpolung Asymmetric 1,5‐Conjugate Addition via Palladium Hydride Catalysis

“…Nucleophilic 1,6‐conjugate addition is a well‐known transformation, and generally involves sequential electronically matched nucleophilic addition and protonation [5, 6] . This widely accepted reaction model has been demonstrated by a series of elegant studies, and enantioselective pathways have also been realized via diverse catalytic systems, including transition metals and organocatalysts (Scheme 1a) [7–21] . This 100 % atom‐economic process can be used to construct enantioenriched stereogenic centers remote from versatile electron‐deficient functional groups and thus represents a highly valuable route to build intriguing chiral skeletons.…”