Bimetallic Catalysis in Stereodivergent Synthesis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(45)

Published: Aug. 2, 2022

Abstract Bimetallic catalysis has emerged as an efficient strategy for the development of new chemical reactions. Importantly, this also provides a simple and powerful platform stereodivergent synthesis, whereby all possible stereoisomers products bearing two stereocenters can be easily prepared from same set starting materials. In Minireview, allylic substitution, propargylic hydrofunctionalization, annulation based on bimetallic been summarized. It is expected that more catalytic systems will developed applied synthesis valuable molecules.

Language: Английский

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Stereodivergent Construction of 1,4‐Nonadjacent Stereocenters via Hydroalkylation of Racemic Allylic Alcohols Enabled by Copper/Ruthenium Relay Catalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(36)

Published: June 28, 2022

An unprecedented hydroalkylation of racemic allylic alcohols and ketimine esters enabled by Cu/Ru relay catalysis has been developed via merging the ruthenium-catalyzed asymmetric borrowing-hydrogen reaction with a copper-catalyzed Michael addition in one-pot procedure. The current method enables efficient preparation highly functionalized δ-hydroxyesters bearing 1,4-nonadjacent stereocenters good yields high levels diastereoselectivity excellent enantioselectivity under mild conditions. full complement four stereoisomers products could be readily accessed orthogonal permutations two chiral metal catalysts. work highlights power for stereodivergent construction that were otherwise inaccessible.

Language: Английский

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Synergistic Dual Catalysis in Stereodivergent Synthesis

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(6), P. 3812 - 3844

Published: Feb. 23, 2024

Chiral skeletons with multiple stereogenic centers widely reside in nature and drugs, their relative absolute configuration often determine physiological or pharmacological properties. Stereodivergent synthesis of chiral molecules is not only great significance, but also highly challenging since the formation one diastereomers inherently preferred most asymmetric reactions. dual catalysis, introduced 2013 by Carreira group, perfectly catered to all requirements for full stereoselectivity control given reactions two catalysts are utilized a synergistic way act independently, has now been arguably efficient strategy realize stereodivergent synthesis. This comprehensive review presents an overview development enabled catalysis past ten years, providing readers fundamental attributes as well ability, scope, mechanism, limitations this strategy.

Language: Английский

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Asymmetric transformations enabled by synergistic dual transition-metal catalysis

Chem Catalysis, Journal Year: 2022, Volume and Issue: 3(1), P. 100455 - 100455

Published: Nov. 17, 2022

Language: Английский

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Cooperative Catalyst‐Enabled Regio‐ and Stereodivergent Synthesis of α‐Quaternary α‐Amino Acids via Asymmetric Allylic Alkylation of Aldimine Esters with Racemic Allylic Alcohols

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(46)

Published: Sept. 26, 2022

We describe cooperative bimetallic catalysis that enables regio-/stereodivergent asymmetric α-allylations of aldimine esters. By employing Et3 B as the key activator, racemic allylic alcohols can be directly ionized to form Pd or Ir-π-allyl species in presence achiral chiral Ir complexes, respectively. The less more substituted termini metal-π-allyl are amenable nucleophilic attack by Cu-azomethine ylide, formation which is simultaneously facilitated B, affording α-quaternary α-amino acids with high regioselectivity and excellent stereoselectivity. use readily available electrophilic precursors represents an improvement from environmental atom/step economy perspective. Computational mechanistic studies reveal crucial role additive origins stereo- regioselectivities analyzing steric effects, dispersion interactions, frontier orbital population.

Language: Английский

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Recent Advances in the Catalytic Asymmetric Friedel–Crafts Reactions of Indoles

ACS Omega, Journal Year: 2022, Volume and Issue: 7(40), P. 35446 - 35485

Published: Oct. 3, 2022

Functionalized chiral indole derivatives are privileged and versatile organic frameworks encountered in numerous pharmaceutically active agents biologically natural products. The catalytic asymmetric Friedel–Crafts reaction of indoles, catalyzed by metal complexes or organocatalysts, is one the most powerful atom-economical approaches to access optically derivatives. Consequently, a wide range electrophilic partners including α,β-unsaturated ketones, esters, amides, imines, β,γ-unsaturated α-keto- α-ketiminoesters, ketimines, nitroalkenes, many others have been successfully employed achieve plethora functionalized moieties. In particular, strategies for C–H functionalization phenyl indoles require incorporation directing blocking group azole ring indole. discovery catalysts which can control enantiodiscrimination has gained great deal attention recent years. This review will provide an updated account on application synthesis diverse derivatives, covering timeframe from 2011 today.

Language: Английский

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Copper/Ruthenium Relay Catalysis for Stereodivergent Access to δ‐Hydroxy α‐Amino Acids and Small Peptides

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(7)

Published: Dec. 29, 2023

Abstract An atom‐ and step‐economical redox‐neutral cascade reaction enabled by asymmetric bimetallic relay catalysis merging a ruthenium‐catalyzed borrowing‐hydrogen with copper‐catalyzed Michael addition has been realized. A variety of highly functionalized 2‐amino‐5‐hydroxyvaleric acid esters or peptides bearing 1,4‐non‐adjacent stereogenic centers have prepared in high yields excellent enantio‐ diastereoselectivity. Judicious selection rational modification the Ru catalysts careful tuning conditions played pivotal role stereoselectivity control as well attenuating undesired α‐epimerization, thus enabling full complement all four stereoisomers that were otherwise inaccessible previous work. Concise stereodivergent synthesis key intermediates for biologically important chiral molecules further showcases synthetic utility this methodology.

Language: Английский

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C3 versus C5 Regioselectivity in the Intramolecular Dehydrative Friedel–Crafts Alkylation of Indole C4-Tethered Carbinols

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Described herein is a mild catalytic dehydrative Friedel-Crafts alkylation of 1,1-diarylalkanols─a challenging reaction with exceedingly rare previous success, presumably because the unfavorable steric hindrance around reactive centers and competitive E1 reaction. Executing in an intramolecular fashion benefiting from high nucleophilicity indole, we have successfully utilized this synthesizing 3,4-fused indoles. Interestingly, strategy could also be applied to access 4,5-fused indoles via modification tether connecting alcohol indole moieties.

Language: Английский

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Asymmetric Synthesis of Chiral 1,2‐Bis(Boronic) Esters Featuring Acyclic, Non‐Adjacent 1,3‐Stereocenters

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(5)

Published: Dec. 15, 2023

The construction of acyclic, non-adjacent 1,3-stereogenic centers, prevalent motifs in drugs and bioactive molecules, has been a long-standing synthetic challenge due to acyclic nucleophiles being distant from the chiral environment. In this study, we successfully synthesized highly valuable 1,2-bis(boronic) esters featuring nonadjacent 1,3-stereocenters. Notably, reaction selectively produces migratory coupling products rather than alternative deborylative allylation or direct byproducts. This approach introduces new activation mode for selective transformations gem-diborylmethane asymmetric catalysis. Additionally, found that other gem-diborylalkanes, previously challenging steric hindrance, also participated reaction. incorporation 1,2-bis(boryl)alkenes facilitated diversification alkenyl two boron moieties our target compounds, thereby enabling access broad array versatile molecules. DFT calculations were performed elucidate mechanism shed light on factors responsible observed excellent enantioselectivity diastereoselectivity. These determined arise ligand-substrate repulsions syn-addition transition state.

Language: Английский

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Enantio- and diastereodivergent synthesis of fused indolizines enabled by synergistic Cu/Ir catalysis

Chemical Science, Journal Year: 2023, Volume and Issue: 14(15), P. 4134 - 4142

Published: Jan. 1, 2023

Highly selective assembly of 2,3-fused indolizines was achieved via a cascade allylation/Friedel–Crafts type reaction with Cu/Ir catalysis. This protocol furnishes stereodivergent synthesis chiral bearing three stereogenic centers excellent results.

Language: Английский

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