Enantioselective Alkyl–Acyl Radical Cross-Coupling Enabled by Metallaphotoredox Catalysis

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Фев. 19, 2025

Radical-radical cross-coupling (RCC) offers a promising approach for carbon-carbon bond formation in organic synthesis, particularly creating complex, three-dimensional molecules. However, achieving both cross- and enantioselectivity RCC reactions has remained significant challenge. Here, we report novel metallaphotoredox platform that enables highly enantioselective decarboxylative coupling of carboxylic acid derivatives with aldehydes. Our strategy leverages independent control over radical generation subsequent through fine-tuning common photocatalyst simple chiral bis(oxazoline) nickel catalyst. This redox-neutral protocol requires no exogenous oxidants or reductants demonstrates broad substrate scope functional group compatibility the synthesis enantioenriched α-aryl α-amino ketones. The ketone products can be readily transformed into valuable β-amino alcohols, streamlining access to these important motifs. Furthermore, showcase potential this more challenging C(sp3)-C(sp3) alkyl-alkyl reactions. unified alkyl-acyl represents advance asymmetric catalysis underscores exploit new mechanisms solve long-standing synthetic problems.

Язык: Английский

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Decarboxylative tandem C-N coupling with nitroarenes via SH2 mechanism

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Май 4, 2022

Abstract Aromatic tertiary amines are one of the most important classes organic compounds in chemistry and drug discovery. It is difficult to efficiently construct from primary via classical nucleophilic substitution due consecutive overalkylation. In this paper, we have developed a radical tandem C-N coupling strategy aromatic commercially available carboxylic acids nitroarenes. A variety can be furnished good yields (up 98%) with excellent functional group compatibility under mild reaction conditions. The use two different also allows for concise synthesis nonsymmetric satisfactory yields. Mechanistic studies suggest intermediacy arylamine–(TPP)Fe(III) species might provide possible evidence an S H 2 (bimolecular homolytic substitution) pathway critical bond formation step.

Язык: Английский

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Ni/Photoredox-Catalyzed C(sp³)–C(sp³) Coupling between Aziridines and Acetals as Alcohol-Derived Alkyl Radical Precursors

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(43), С. 20067 - 20077

Опубликована: Окт. 18, 2022

Aziridines are readily available C(sp3) precursors that afford valuable β-functionalized amines upon ring opening. In this article, we report a Ni/photoredox methodology for C(sp3)-C(sp3) cross-coupling between aziridines and methyl/1°/2° aliphatic alcohols activated as benzaldehyde dialkyl acetals. Orthogonal activation modes of each alkyl coupling partner facilitate cross-selectivity in the bond-forming reaction: acetal is via hydrogen atom abstraction β-scission bromine radical (generated situ from single-electron oxidation bromide), whereas aziridine at Ni center reduction. We demonstrate an Ni(II) azametallacycle, conventionally proposed cross-coupling, not intermediate productive cross-coupling. Rather, stoichiometric organometallic linear free energy relationship studies indicate proceeds Ni(I) oxidative addition, previously unexplored elementary step.

Язык: Английский

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Discovery, structure and mechanism of a tetraether lipid synthase

Nature, Год журнала: 2022, Номер 609(7925), С. 197 - 203

Опубликована: Июль 26, 2022

Archaea synthesize isoprenoid-based ether-linked membrane lipids, which enable them to withstand extreme environmental conditions, such as high temperatures, salinity, and low or pH values1-5. In some archaea, Methanocaldococcus jannaschii, these lipids are further modified by forming carbon-carbon bonds between the termini of two lipid tails within one glycerophospholipid generate macrocyclic archaeol from glycerophospholipids macrocycle glycerol dibiphytanyl tetraether (GDGT)1,2. GDGT contains 40-carbon chains (biphytanyl chains) that span both leaflets membrane, providing enhanced stability conditions. How specialized formed has puzzled scientists for decades. The reaction necessitates coupling completely inert sp3-hybridized carbon centres, which, our knowledge, not been observed in nature. Here we show gene product mj0619 M. encodes a radical S-adenosylmethionine enzyme, is responsible biphytanyl chain formation during synthesis lipids6. Structures enzyme presence four metallocofactors: three [Fe4S4] clusters mononuclear rubredoxin-like iron ion. vitro mechanistic studies Csp3-Csp3 bond takes place on fully saturated archaeal substrates involves an intermediate substrate sulfur clusters. Our results only establish biosynthetic route but also improve use GDGT-based paleoclimatology indices7-10.

Язык: Английский

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Two-in-one metallaphotoredox cross-couplings enabled by a photoactive ligand

Chem, Год журнала: 2022, Номер 8(9), С. 2419 - 2431

Опубликована: Июнь 9, 2022

Язык: Английский

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