Chiral Aldehyde Catalysis-Enabled Asymmetric α-Functionalization of Activated Primary Amines

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(5), P. 776 - 794

Published: Feb. 21, 2024

ConspectusThe development of catalytic activation modes provides a reliable and effective platform for designing new enantioselective reactions preparing chiral molecules with diverse structures. Chiral aldehyde catalysis is an attractive concept in asymmetric catalysis, which utilizes catalyst to promote the hydroamination allylic amines, α-functionalization primary or transamination α-keto esters. Typically, aldehyde-catalyzed amines efficient straightforward method synthesis α-functionalized does not require any additional protection deprotection manipulations amine group. However, achieving stereoselective transformations high efficiency enantioselectivity by this strategy has remained intractable challenge.This Account summarizes our endeavors application catalysis. Using as catalyst, we reported α-C alkylation 2-aminomalonate 3-indolylmethanol 2014, represents first activated amine. Subsequently, several axially catalysts were continuously prepared using BINOL starting material, their applications explored. On one hand, they used organocatalysts realize various α-amino acid esters, such 1,4-addition toward conjugated enones/α,β-unsaturated diesters cyclic 1-azadienes well α-arylation/allylation benzylation corresponding halohydrocarbons. Notably, taking advantage difference distribution sites between two catalysts, disclosed diastereodivergent 1,6-conjugated addition Mannich reactions. other potential cooperative transition metal also been demonstrated. Enabled combination aldehyde, palladium complex, Lewis acid, α-allylation amino esters allyl alcohol was established. Moreover, ternary system successfully 1,3-dienes, allenes, allenylic 1,3-disubstituted arylmethanol cascade Heck-alkylation reaction. The nickel complex allows α-propargylation propargylic excellent enantioselectivities. These provide large library optically active acids. With those key building blocks, formal multiple natural products biologically significant unnatural accomplished. This includes stereodivergent pyrrolizidine alkaloid NP25302 product (

Language: Английский

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The Catalytic Asymmetric Allylic Alkylation of Acyclic Enolates for the Construction of Quaternary and Tetrasubstituted Stereogenic Centres

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(20)

Published: Jan. 29, 2024

To facilitate the discovery and development of new pharmaceuticals, demand for novel stereofunctionalised building blocks has never been greater. Whilst molecules bearing quaternary tetrasubstituted stereogenic centres are ideally suited to explore untapped areas chemical space, asymmetric construction ofsterically congested carbon remains a longstanding challenge in organic synthesis. The enantioselective assembly acyclic is even more demanding due need restrict much wider range geometries conformations intermediates involved. In this context, catalytic allylicalkylation (AAA) prochiral nucleophiles, namely enolates, become an indispensable tool access linearα-quaternary andα-tetrasubstituted carbonyl compounds. However, unlike AAA cyclic enolates with fixed enolate geometry, achieve high levels stereocontrol stereoselectivity enolisation must be considered. aim review offer acomprehensivediscussion reactions their analogues generate chiral using metal, non-metal dual catalysis, particular focus given control geometry its impact on stereochemical outcome reaction.

Language: Английский

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Asymmetric three-component Tsuji–Trost allylation reaction enabled by chiral aldehyde/palladium combined catalysis

Chemical Science, Journal Year: 2024, Volume and Issue: 15(26), P. 10232 - 10236

Published: Jan. 1, 2024

An asymmetric three-component allylation reaction is achieved under the promotion of chiral aldehyde/palladium combined catalysis via mixed Heck/allylation cascades.

Language: Английский

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Direct Enantioselective Allylic Alkylation of α-Amino Esters to Quaternary Glutamates via Strategic Pyridoxal Catalyst Design

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

The difficulty for N-unprotected α-substituted glycinates as α-C nucleophiles originates from both competing N nucleophilic interference and steric hindrance of the α substituent, which makes direct asymmetric alkylation with Morita-Baylis-Hillman (MBH) adducts especially challenging. Given wide utilization α-quaternary chiral glutamic acid derivatives in therapeutic studies, we took advantage biomimetic carbonyl catalysis to achieve their efficient synthesis. A bifunctional centrally pyridoxal, featured an expanded catalytic cavity reduced around aldehyde group, was designed synthesized. In this work, describe novel pyridoxal enabled MBH acetates. broad range multiple modifications were produced high reactivity excellent stereocontrol.

Language: Английский

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Core Structure-Oriented Asymmetric α-Allenylic Alkylation of Amino Acid Esters Enabled by Chiral Aldehyde/Palladium Catalysis

Organic Letters, Journal Year: 2023, Volume and Issue: 26(1), P. 153 - 159

Published: Dec. 22, 2023

Aiming at the reported chiral synthons leading to manzacidins A and D, here we report a highly efficient catalytic asymmetric α-allenylic alkylation reaction of NH2-unprotected amino acid esters that is promoted by combined aldehyde/palladium catalysis. Fifty examples unnatural α,α-disubstituted are with good-to-excellent yields stereoselectivities. Based on this methodology, key intermediate manzacidin C its other three stereoisomers prepared accordingly.

Language: Английский

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Dual-Catalysis-Enabled Construction of Vicinal Stereogenic Centers through Diastereo- and Enantioselective Allylic Substitution

Synthesis, Journal Year: 2024, Volume and Issue: 56(22), P. 3365 - 3376

Published: April 15, 2024

Abstract Vicinal stereogenic centers represent prevalent structural motifs in organic synthetic chemistry, and their construction poses a longstanding challenge. Transition-metal-catalyzed asymmetric allylic substitution has become well-established enantioselective C–C bond-forming reaction. When these reactions involve prochiral nucleophile an electrophile with terminal substituent, the creation of vicinal becomes feasible. However, despite remarkable achievements having been accomplished, realizing this transformation precise control over both enantio- diastereoselectivity remains significant To address stereoselective challenges, introduction second catalyst to transition-metal-catalyzed alkylation during bond formation proven particularly fruitful. In short review, we aim highlight recent advances dual catalysis that enable diastereo- substitutions. 1 Introduction 2 Construction Stereogenic Centers by Organo Metal Dual Catalysis 2.1 Chiral Phase-Transfer Transition-Metal 2.2 Amine 2.3 NHC 2.4 Aldehyde 2.5 Lewis Base 3 3.1 Acidic Iridium 3.2 Palladium 3.3 Ruthenium 3.4 Other Advancements through Synergistic Bimetallic Enabling Asymmetric Allylic Alkylation 4 Conclusions Future Outlook

Language: Английский

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The Development of Aldehyde Catalytic System

Chemistry - An Asian Journal, Journal Year: 2023, Volume and Issue: 18(22)

Published: Sept. 27, 2023

Aldehyde catalysts have proven to be highly effective in facilitating and accelerating a wide range of challenging transformations organic chemistry. This article is structured into three main sections, focusing on the utilization aldehydes as organocatalysts, aldehydes/transition metals catalytic systems, photochemical initiators. Finally, we provide concise summary advancements this fascinating research field, offering our perspectives insights.

Language: Английский

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Asymmetric α-Allylation for the Synthesis of α,α-Disubstituted Amino Acids with Vicinal Chiral Centers

Synfacts, Journal Year: 2023, Volume and Issue: 19(11), P. 1166 - 1166

Published: Oct. 14, 2023

Key words three-component reaction - carboamination chiral aldehydes palladium catalysis radical coupling α-aryl α-amino acids quaternary amino

Language: Английский

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