Studies Toward Improved Enantiocontrol in the Asymmetric Cu-Catalyzed Reductive Coupling of Ketones and Allenamides: 1,2-Aminoalcohol Synthesis

Organic Letters, Journal Year: 2023, Volume and Issue: 25(9), P. 1425 - 1430

Published: Feb. 27, 2023

Herein, we report the development of an improved system for Cu-catalyzed enantioselective reductive coupling ketones and allenamides through optimization allenamide to avoid on-cycle rearrangement. High enantioselectivities could be obtained a variety ketones. Use acyclic described herein selectively generated anti-diastereomers in contrast cyclic that were previously shown favor syn-form. A rationale this change diastereoselectivity is also presented.

Language: Английский

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Enantioselective Synthesis of α‐Hydroxy Allyl Ketones via BINAP‐CuH‐Catalyzed Hydroacylation

Angewandte Chemie, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Abstract Catalytic hydrocupration of unsaturated carbon‐carbon bonds to generate organometallic nucleophiles has recently become an attractive alternative conventional stoichiometric reagents in the stereoselective synthesis. Herein, we have developed efficient and economical method synthesize enantiopure α ‐hydroxy allyl ketones via a copper hydride (CuH)‐catalyzed hydroacylation alkoxyallenes, significant advancement given scarcity reports on such scaffolds literature. DFT calculations reveal that this reaction proceeds through nucleophilic attack kinetically favourable Z ‐selective allyl‐copper intermediate acid anhydrides six‐membered chair‐like transition state, stabilized by strongly non‐covalent interactions ultimately leads high level enantioselectivities using simple BINAP ligand. This successfully overcomes challenges over‐reduction carbonyl functionality presence CuH‐complex, olefin isomerization highly enolizable ‐stereocenter, which can lead erosion enantioselectivities, making our strategy desirable. The exhibits wide range substrate scope including symmetrical as well carbonic with both aromatic, aliphatic substitutions. In addition, ‐substituted provide exclusive syn α,α′ ‐disubstituted excellent enantiomeric ratios, where allylation occurs one carbonyls containing matched α‐ stereocenter, confirmed mechanistic studies.

Language: Английский

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Enantioselective Synthesis of α‐Hydroxy Allyl Ketones via BINAP‐CuH‐Catalyzed Hydroacylation

Angewandte Chemie International Edition, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Abstract Catalytic hydrocupration of unsaturated carbon‐carbon bonds to generate organometallic nucleophiles has recently become an attractive alternative conventional stoichiometric reagents in the stereoselective synthesis. Herein, we have developed efficient and economical method synthesize enantiopure α ‐hydroxy allyl ketones via a copper hydride (CuH)‐catalyzed hydroacylation alkoxyallenes, significant advancement given scarcity reports on such scaffolds literature. DFT calculations reveal that this reaction proceeds through nucleophilic attack kinetically favourable Z ‐selective allyl‐copper intermediate acid anhydrides six‐membered chair‐like transition state, stabilized by strongly non‐covalent interactions ultimately leads high level enantioselectivities using simple BINAP ligand. This successfully overcomes challenges over‐reduction carbonyl functionality presence CuH‐complex, olefin isomerization highly enolizable ‐stereocenter, which can lead erosion enantioselectivities, making our strategy desirable. The exhibits wide range substrate scope including symmetrical as well carbonic with both aromatic, aliphatic substitutions. In addition, ‐substituted provide exclusive syn α,α′ ‐disubstituted excellent enantiomeric ratios, where allylation occurs one carbonyls containing matched α‐ stereocenter, confirmed mechanistic studies.

Language: Английский

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Recent advancement on metal free hydroamination reaction of C-C multiple bonds.

Tetrahedron, Journal Year: 2025, Volume and Issue: unknown, P. 134625 - 134625

Published: March 1, 2025

Language: Английский

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Enantioselective 1,4-Borylamination Enabled by Copper Catalysis

Synlett, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Abstract Compounds bearing both boryl and amino groups are highly valuable synthons in organic synthesis. However, while enantioselective 1,1- 1,2-borylamination reactions have been developed, processes enabling distal borylamination rarely investigated. Here, we present an 1,4-borylamination reaction, achieved through a copper-catalyzed cascade hydroborylation hydroamination of arylidenecyclopropanes. This four-component reaction provides direct access to enantioenriched 4-aminoalkylboronate products with high chemo-, site-, enantioselectivity. The versatility these was demonstrated their broad transformations extensive applications the synthesis various drug core structures. Additionally, preliminary mechanistic studies were conducted investigate pathway, intermediates, chemo- site-selectivity.

Language: Английский

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