1,2-Additions on Chiral N-Sulfinylketimines: An Easy Access to Chiral α-Tertiary Amines

Carret, Sébastien; Poisson, Jean‐François; Berthiol, Florian; Achuenu, Chukuka

doi:10.1055/s-0041-1737563

Cited by 6 publications

(1 citation statement)

References 165 publications

(127 reference statements)

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“…While catalytic methods are emerging for their synthesis, most prominently proceeding through the Giese-type functionalization of an α-amino radical, these methods are fundamentally limited in terms of accessible chemical space due to the incorporation of the structural signature associated with the alkene Giese acceptor . Arguably, one of the best-established strategies toward the synthesis of α-tertiary amines is the 1,2-addition of carbon-centered nucleophiles. − However, these examples are invariably limited to activated, preformed imines. While unquestionably a powerful strategy, there are notably few examples of addition to nonactivated dialkyl imines, likely due to competitive α-deprotonation resulting from the basic nature of the organometallic nucleophile.…”

Section: α-Tertiary Amine Synthesismentioning

confidence: 99%

Multicomponent Synthesis of α-Branched Amines via a Zinc-Mediated Carbonyl Alkylative Amination Reaction

Phelps,

Kumar,

Robinson

et al. 2024

J. Am. Chem. Soc.

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Methods for the synthesis of α-branched alkylamines are important due to their ubiquity in biologically active molecules. Despite the development of many methods for amine preparation, C(sp 3 )-rich nitrogen-containing compounds continue to pose challenges for synthesis. While carbonyl reductive amination (CRA) between ketones and alkylamines is the cornerstone method for α-branched alkylamine synthesis, it is sometimes limited by the sterically demanding condensation step between dialkyl ketones and amines and the more restricted availability of ketones compared to aldehydes. We recently reported a "higher-order" variant of this transformation, carbonyl alkylative amination (CAA), which utilized a halogen atom transfer (XAT)mediated radical mechanism, enabling the streamlined synthesis of complex α-branched alkylamines. Despite the efficacy of this visible-light-driven approach, it displayed scalability issues, and competitive reductive amination was a problem for certain substrate classes, limiting applicability. Here, we report a change in the reaction regime that expands the CAA platform through the realization of an extremely broad zinc-mediated CAA reaction. This new strategy enabled elimination of competitive CRA, simplified purification, and improved reaction scope. Furthermore, this new reaction harnessed carboxylic acid derivatives as alkyl donors and facilitated the synthesis of α-trialkyl tertiary amines, which cannot be accessed via CRA. This Zn-mediated CAA reaction can be carried out at a variety of scales, from a 10 μmol setup in microtiter plates enabling high-throughput experimentation, to the gramscale synthesis of medicinally-relevant compounds. We believe that this transformation enables robust, efficient, and economical access to α-branched alkylamines and provides a viable alternative to the current benchmark methods.

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Section: α-Tertiary Amine Synthesismentioning

confidence: 99%

Multicomponent Synthesis of α-Branched Amines via a Zinc-Mediated Carbonyl Alkylative Amination Reaction

Phelps,

Kumar,

Robinson

et al. 2024

J. Am. Chem. Soc.

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Evans’ Chiral Auxiliary‐Based Asymmetric Synthetic Methodology and Its Modern Extensions

Chen,

Huang

2023

Eur J Org Chem

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Although the asymmetric catalysis has made a spurt of progress, the use of chiral auxiliaries remains crucial in asymmetric synthesis due to both the reliability and versatility of the methods, and the predictability of stereochemistry of the reactions. Up to date, Evans’ chiral non‐racemic oxazolidinone‐based asymmetric synthetic methodology is still widely used in asymmetric synthesis. More importantly, the Evans asymmetric synthetic methodology turned out to be a fruitful source of inspiration for the development of related asymmetric synthetic methodologies. However, although reviews on the application of Evans’ asymmetric synthetic methodology in both organic synthesis and medicinal chemistry continually to appear in the literature, a comprehensive review dedicating to the extensions of Evans’ chiral non‐racemic oxazolidinone‐based asymmetric methodology remains elusive. In this review, we summarize the extensions of the Evans asymmetric methodology, which cover: (1) the modification of the chiral oxazolidinone auxiliaries; (2) the extension of the Evans’ asymmetric aldol reaction from Evans’ syn‐aldol to other diastereomeric aldol adducts; (3) the extension of the asymmetric reaction types; (4) the extension of chiral imide‐type substrates to N‐alkenyl, N‐allenenyl and N‐alkynyl oxazolidinones; (5) the achiral oxazolidinone‐based asymmetric catalysis; (6) the catalytic transformation of Evans’ products; and (7) the straightforward transformations of Evans’ chiral products to other classes of compounds than the chiral carboxylic acids, esters, alcohols, and Weinreb amides.

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Biocatalytic Amine Synthesis

Abdelraheem

Damian

Mutti

2024

Comprehensive Chirality

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1,2-Additions on Chiral N-Sulfinylketimines: An Easy Access to Chiral α-Tertiary Amines

Cited by 6 publications

References 165 publications

Multicomponent Synthesis of α-Branched Amines via a Zinc-Mediated Carbonyl Alkylative Amination Reaction

Multicomponent Synthesis of α-Branched Amines via a Zinc-Mediated Carbonyl Alkylative Amination Reaction

Evans’ Chiral Auxiliary‐Based Asymmetric Synthetic Methodology and Its Modern Extensions

Biocatalytic Amine Synthesis

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