Highly enantioselective carbene insertion into N–H bonds of aliphatic amines

Li, Maolin; Yu, Jinhan; Li, Yi-Hao; Zhu, Shou‐Fei; Zhou, Qi‐Lin

doi:10.1126/science.aaw9939

Cited by 222 publications

(103 citation statements)

References 64 publications

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“…12,13 This strategy has been perfected over the last een years and a diverse array of diazo compounds and nitrogen nucleophiles can now be coupled with high enantioselectivities. [14][15][16][17][18] The most recent achievement in this eld was described by Zhou 18 in 2019, where a combination of a copper(I)-scorpionate complex, together with an optically active thiourea, led to high enantioselectivities when strongly coordinating aliphatic amines were reacted in the presence of diazo esters. Despite these great advances, each catalytic system described so far is still only efficient for a specic combination of substrates.…”

Section: Introductionmentioning

confidence: 99%

Cooperative copper-squaramide catalysis for the enantioselective N–H insertion reaction with sulfoxonium ylides

2021

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Section: Introductionmentioning

confidence: 99%

Cooperative copper-squaramide catalysis for the enantioselective N–H insertion reaction with sulfoxonium ylides

2021

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“…The insertion of metal‐carbene species into N−H bond is one of the efficient and rapid route for synthesizing various compounds such as α‐amino esters, dipeptides and N‐heterocycles [43] . This method is also useful in the late‐stage functionalization of natural compounds or complex molecules.…”

Section: Iron‐based Chemical Catalystsmentioning

confidence: 99%

Recent Advances in Iron‐Catalyzed Chemical and Enzymatic Carbene‐Transfer Reactions

Kaur

Tyagi

2021

Adv Synth Catal

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The use of diazo compounds in the transition‐metal‐catalyzed coupling reactions to form C−C and C−X (X=O, S, N, Si, P etc.) bonds have been a well established approach in organic synthesis. In this context, various transition metals such as Pd, Cu, Rh, Ni, Co, Fe, Ir etc. have proved useful to generate a metal‐carbene intermediate which subsequently undergoes carbene transfer or insertion to form C−C, C−Si or C‐heteroatom bonds. However, the use of most abundant, cheaper and environmentally benign metal such as iron to catalyze carbene‐transfer reactions has attracted considerable attention in the last few years. Iron is the second most abundant transition metal in nature and also an integral part of various biological systems which make it highly valuable to use as a catalyst in organic chemistry. This review summarizes the efforts made after 2013 in the area of iron‐catalyzed chemical and enzymatic carbene‐transfer reactions using diazo compounds as carbene precursor.

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“…14,15,36,37 The difficulty in achieving high enantioselectivity in these reactions have been attributed to catalyst poisoning by the nucleophilic amine and facile dissociation of the ylide intermediate from the metal center. 14,37 While significant progress was made toward overcoming these challenges, these chemocatalytic protocols require the use of precious metals (e.g., Rh, Pd), [38][39][40][41] synthetically challenging chiral ligands and/or co-catalysts, 38,[42][43][44] and/or are restricted to -aryl diazo compounds, 40,41,45 with only a few exceptions. 43,44 In this context, the development of biocatalytic alternatives would be therefore highly desirable as it will contribute to the development of sustainable and environmentally benign approaches for realizing these transformations.…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Synthesis of Chiral Amines via Biocatalytic Carbene N–H Insertion

et al. 2020

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Optically active amines represent highly valuable building blocks for the synthesis of advanced pharmaceutical intermediates, drug molecules, and biologically active natural products. Hemoproteins have recently emerged as promising biocatalysts for the formation of C-N bonds via carbene transfer, but asymmetric N-H carbene insertion reactions using these or other enzymes have so far been elusive. Here, we report the successful development of a biocatalytic strategy for the asymmetric N-H carbene insertion of aromatic amines with 2-diazopropanoate esters using engineered variants of myoglobin. High activity and stereoinduction in this reaction could be achieved by tuning the chiral environment around the heme cofactor in the metalloprotein in combination with catalyst-matching and tailoring of the diazo reagent. Using this approach, an efficient biocatalytic protocol for the synthesis of a broad range of substituted aryl amines with up to 82% ee was obtained. In addition, a stereocomplementary catalyst useful to access the mirrorimage form of the N-H insertion products was identified. This work paves the way to asymmetric amine synthesis via biocatalytic carbene transfer, and the present strategy based on the synergistic combination of protein and diazo reagent engineering is expected to prove useful in the context of these as well as other challenging asymmetric carbene transfer reactions. File list (2) download file view on ChemRxiv AsymmNH_Main_final (1).pdf (743.83 KiB) download file view on ChemRxiv AsymmNH_Main_final (1).docx (579.50 KiB)

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Highly enantioselective carbene insertion into N–H bonds of aliphatic amines

Cited by 222 publications

References 64 publications

Cooperative copper-squaramide catalysis for the enantioselective N–H insertion reaction with sulfoxonium ylides

Cooperative copper-squaramide catalysis for the enantioselective N–H insertion reaction with sulfoxonium ylides

Recent Advances in Iron‐Catalyzed Chemical and Enzymatic Carbene‐Transfer Reactions

Enantioselective Synthesis of Chiral Amines via Biocatalytic Carbene N–H Insertion

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