Heme‐Enzymatic Biocatalysis for C−C or C−N Bond Formation

ChemCatChem, Год журнала: 2024, Номер 16(21)

Опубликована: Июль 15, 2024

Abstract The C−C or C−N bond formation is critical in the synthesis of pharmaceuticals and other value‐added products; however, traditional metal‐catalysed has brought about environmental resource issues. A plethora engineered heme‐dependent enzymes, such as cytochrome P450, have exhibited enormous potential biocatalysis for formation. With development computational spectroscopic methods, mechanisms underlying heme‐catalysed been extensively investigated. In presence carbene nitrene precursor, an active iron porphyrin ( IPC ) IPN formed, which subsequently reacts with a second substrate to form new bonds. Apart from widely studied / ‐facilitated catalytic pathway, halide‐initiated radical cyclization pathway Cpd‐I‐catalysed diradical also proposed. These mechanistic insights enabled rational engineering de novo design heme enzymes. This review summarises recent advances enzymatic presents successful applications mechanism‐based enzyme design. It would shed light on tailored biocatalysts complex but valuable industrial products.

Язык: Английский

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Selective C−H Bond Functionalization of Unprotected Indoles by Donor‐Acceptor Carbene Insertion

Advanced Synthesis & Catalysis, Год журнала: 2023, Номер 366(4), С. 844 - 851

Опубликована: Июль 3, 2023

Abstract Copper catalysts containing alkoxydiaminophosphine (ADAP) ligand catalyze the selective C3−H functionalization of unprotected indoles upon carbene transfer from donor‐acceptor diazo compounds, N−H bond remaining unaltered during transformation. Mechanistic studies, including DFT calculations, allows proposing existence two competitive pathways, none them occurring through formation cyclopropane intermediates, at variance with previously reported systems.

Язык: Английский

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Role of mutations in a chemoenzymatic enantiodivergent C(sp³)–H insertion: exploring the mechanism and origin of stereoselectivity

Chemical Science, Год журнала: 2023, Номер 14(33), С. 8810 - 8822

Опубликована: Янв. 1, 2023

New-to-nature enzymes have emerged as powerful catalysts in recent years for streamlining various stereoselective organic transformations. While synthetic strategies employing engineered witnessed proliferating success, there is limited clarity on the mechanistic front and more so when considering molecular-level insights into role of selected mutations, dramatically escalating catalytic competency selectivity. We investigated mechanism correlation between mutations exquisite stereoselectivity a lactone carbene insertion C(sp3)-H bond substituted aniline, catalyzed by two mutants cytochrome P450 variant, "P411" (engineered through directed evolution) which axial cysteine has been mutated to serine, utilizing computational tools. The pivotal S264 L/R328 active site delineated computationally using cluster models, thus rationalizing enantiodivergence. This report provides much-needed origin enantiodivergence, furnishing framework understanding anchoring effects H-bond donor residues with ring. study expected important implications rational design stereodivergent toward successful silico enzyme designing.

Язык: Английский

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Mechanistic Insight into Palladium‐Catalyzed Asymmetric Alkylation of Indoles with Diazoesters Employing Bipyridine‐N,N’‐dioxides as Chiral Controllers

Advanced Synthesis & Catalysis, Год журнала: 2023, Номер 366(1), С. 121 - 133

Опубликована: Ноя. 21, 2023

Abstract Metal‐catalyzed asymmetric alkylation of indoles with α‐diazoesters is well‐known, however, the underlying mechanisms this reaction, particularly origin stereoselectivity, remain uncertain. For Pd catalysis, we address cutting‐edge challenge from two complementary viewpoints – i) molecular level regarding a single catalytically active center; and ii) nano‐level species investigating factors favoring appearance preferred catalytic centers. The formation was monitored by structural methods (NMR ESI‐MS), metal particles were characterized electron microscopy (SEM, EDX). On level, chiral bipyridine‐ N,N’ ‐dioxides proved to be competent controllers. kinetic DFT computational data revealed crucial role water in rate selectivity determining steps showed that enantioselectivity process controlled protodepalladation step. nano‐scale, important effect catalyst precursor on overall reaction performance shown.

Язык: Английский

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A Crossover between Conventional Cross-Coupling and Carbene Insertion Reaction Pathways in a Pd Catalyzed C(sp2)-H Insertion

Опубликована: Авг. 9, 2023

Computational methods (Density Functional Theory) along with experimental tools are used to probe the mechanism and stereocontrol in a Pd(II)-catalyzed enantioselective C–H insertion reaction. The mechanistic aspects reveal crossover between general transition metal-catalyzed carbene reactions typical Pd-catalyzed cross-coupling reactions. We demonstrate intermediacy of metal hydride species which contrasts previously studied routes taken case all other metals (Rh, Fe, Au, Cu, etc.). Detailed investigation into origin stereoselectivity again throws up new paradigm wherein arises during formation metallocarbene itself. Novel illustrated this report provide crucial insights differential reactivity exhibited by Pd

Язык: Английский

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C–H functionalization of indole with diazoacetate catalyzed by a CCC-NHC Ir (III) dimer complex

Tetrahedron Letters, Год журнала: 2023, Номер 125, С. 154610 - 154610

Опубликована: Июнь 21, 2023

Язык: Английский

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Three‐component allylic alkylation reaction of α‐diazo ketones with water and allyl carbonates for construction of homoallylic alcohols

Advanced Synthesis & Catalysis, Год журнала: 2024, Номер 366(17), С. 3616 - 3623

Опубликована: Июнь 20, 2024

Abstract A three‐component allylic alkylation reaction of α‐diazo ketones, water and allyl carbonate under the cooperative catalysis Rh 2 (OAc) 4 , Pd (dba) 3 Brønsted acid was disclosed. This method provides an expeditious access to α‐keto homoallylic alcohols in good high yields. Controlled experiments support that transformations proceed through cross‐interception two active intermediates Pd‐allyl species enol derived from oxonium ylides. Moreover, synthetic generated products enable creation motifs enriched with dense functional groups, underscoring their potential as valuable building blocks.

Язык: Английский

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Cesium and Phenoxide Interaction Enabled by Rh Overrides the Innate Solvent-Mediated Chemoselectivity

ACS Catalysis, Год журнала: 2024, Номер 14(16), С. 12351 - 12358

Опубликована: Авг. 5, 2024

DLPNO-CCSD(T) calculations are carried out to understand the distinctive chemoselectivity in a Rh(II)-catalyzed carbene insertion into C(sp2)–H bond unprotected phenols without preinstalled directing groups. As per conventional rules of solvation and separated ion pair polar aprotic solvents like acetonitrile, reaction should have resulted an O–H insertion. However, our reveal transition state model that helps overriding innate acetonitrile. It involves explicit participation added Cs2CO3 base, where interaction between phenoxide oxygen Cs cation, but not as metal-bound phenoxide, is crucial for controlling chemoselectivity. Our study will be helpful developing further reactions with broad catalyst, substrate, solvent scope.

Язык: Английский

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