Mechanistically Guided Workflow for Relating Complex Reactive Site Topologies to Catalyst Performance in C–H Functionalization Reactions DOI
Ryan C. Cammarota, Wenbin Liu, John Bacsa

и другие.

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(4), С. 1881 - 1898

Опубликована: Янв. 24, 2022

Leveraging congested catalyst scaffolds has emerged as a key strategy for altering innate substrate site-selectivity profiles in C-H functionalization reactions. Similar to enzyme active sites, optimal small molecule catalysts often feature reactive cavities tailored controlling approach trajectories. However, relating three-dimensional shape reaction output remains formidable challenge, part due the lack of molecular features capable succinctly describing complex site topologies terms numerical inputs machine learning applications. Herein, we present new set descriptors, "Spatial Molding Approachable Rigid Targets" (SMART), which have applied quantify spatial constraints an expansive library dirhodium and predict 1-bromo-4-pentylbenzene via donor/acceptor carbene intermediates. Optimal terminal methylene position was obtained with Rh2(S-2-Cl-5-MesTPCP)4 (30.9:1 rr, 14:1 dr, 87% ee), while at electronically activated benzylic increasingly favored Rh2(TPCP)4 lacking ortho-Cl, Rh2(S-PTAD)4, Rh2(S-TCPTAD)4, respectively. Intuitive global models 25 disparate were developed multivariate linear regression explicitly assess contributing roles steric congestion dirhodium-carbene electrophilicity functionalization. The workflow utilizes classification extract descriptors only conformers, nuance that may be widely applicable establishing close correspondence between ground-state model systems transition states. Broader still, SMART are amenable delineating salient reactivity other chemical biological contexts.

Язык: Английский

Navigating the Unnatural Reaction Space: Directed Evolution of Heme Proteins for Selective Carbene and Nitrene Transfer DOI Creative Commons
Yang Yang, Frances H. Arnold

Accounts of Chemical Research, Год журнала: 2021, Номер 54(5), С. 1209 - 1225

Опубликована: Янв. 25, 2021

ConspectusDespite the astonishing diversity of naturally occurring biocatalytic processes, enzymes do not catalyze many transformations favored by synthetic chemists. Either nature does care about specific products, or if she does, has adopted a different strategy. In cases, appropriate reagents used chemists are readily accessible to biological systems. Here, we discuss our efforts expand catalytic repertoire encompass powerful reactions previously known only in small-molecule catalysis: formation and transfer reactive carbene nitrene intermediates leading broad range including products with bonds biology. light structural similarity iron (Fe═C(R1)(R2)) (Fe═NR) oxo (Fe═O) intermediate involved cytochrome P450-catalyzed oxidation, have precursors that systems encountered repurposed P450s natural world. The resulting protein catalysts fully genetically encoded function intact microbial cells cell-free lysates, where their performance can be improved optimized directed evolution. By leveraging promiscuity P450 enzymes, evolved transferases exhibiting excellent activity toward these new-to-nature reactions. Since initial report 2012, number other heme proteins myoglobins, protoglobins, cytochromes c also been found engineered promote unnatural transfer. Due altered active-site environments, often displayed complementary activities selectivities P450s.Using wild-type proteins, others described selective reactions, cyclopropanation, cyclopropenation, Si–H insertion, B–H C–H insertion. Similarly, variety asymmetric processes aziridination, sulfide imidation, amidation, and, most recently, amination demonstrated. scopes state-of-the-art based on transition-metal catalysts, making biocatalysts valuable addition chemist's toolbox. Moreover, enabled exquisite regio- stereocontrol imposed enzyme catalyst, this platform provides an exciting opportunity address challenging problems modern chemistry catalysis, ones eluded for decades.

Язык: Английский

Процитировано

254
Catalytic Enantioselective Functionalizations of C–H Bonds by Chiral Iridium Complexes DOI
Łukasz Woźniak, Jin-Fay Tan, Qui-Hien Nguyen

и другие.

Chemical Reviews, Год журнала: 2020, Номер 120(18), С. 10516 - 10543

Опубликована: Сен. 8, 2020

The development of catalytic enantioselective transformations, enabling the construction complex molecular scaffolds from simple precursors, has been a long-standing challenge in organic synthesis. Recent achievements transition-metal catalyzed functionalizations carbon–hydrogen (C–H) bonds represent promising pathway toward this goal. Over last two decades, iridium catalysis evolved as valuable tool stereocontrolled synthesis chiral molecules via C–H activation. iridium-based systems with various ligand classes, well studies their reaction mechanisms, resulted dynamic progress area. This review aims to present comprehensive picture by complexes emphasis on mechanisms activation step.

Язык: Английский

Процитировано

212
Dioxazolones: Stable Substrates for the Catalytic Transfer of Acyl Nitrenes DOI Creative Commons

Kaj M. van Vliet,

Bas de Bruin

ACS Catalysis, Год журнала: 2020, Номер 10(8), С. 4751 - 4769

Опубликована: Март 30, 2020

Dioxazolones are a convenient class of acyl nitrene transfer reagents. Their application in homogeneous transition-metal catalysis has led to many new amidation reactions. typically activated by transition metals at relatively low reaction temperatures. The metal nitrenoids formed decarboxylative activation dioxazolones generally electron deficient and commonly react concerted fashion. "Intermolecular" insertion reactions involving preactivated C–H bonds ("inner-sphere" mechanism) easily compete with the Curtius-type rearrangement, but for intramolecular "direct" transfer/insertion nonpreactivated substrates (i.e., without preceding formation metal–carbon or metal–hydride bonds) extensive ligand optimization is important prevent such unwanted side ease dioxazolone synthesis, CO2 gas as sole byproduct from dioxazolones, importance general development several interesting producing N-aryl amides, oxazoles, lactams. Since proceeds under mild conditions, stereo- enantioselective also possible, which useful synthesis bioactive nitrogen-containing compounds. This review provides an overview these reported recent years.

Язык: Английский

Процитировано

178
Nitrene transfer catalysts for enantioselective C–N bond formation DOI
Minsoo Ju, Jennifer M. Schomaker

Nature Reviews Chemistry, Год журнала: 2021, Номер 5(8), С. 580 - 594

Опубликована: Июнь 28, 2021

Язык: Английский

Процитировано

171
Catalytic enantioselective C(sp3)–H functionalization involving radical intermediates DOI Creative Commons
Chi Zhang, Zhong‐Liang Li, Qiang‐Shuai Gu

и другие.

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Янв. 20, 2021

Abstract Recently, with the boosted development of radical chemistry, enantioselective functionalization C( sp 3 )–H bonds via a pathway has witnessed renaissance. In principle, two distinct catalytic modes, distinguished by steps in which stereochemistry is determined (the formation step or step), can be devised. This Perspective discusses state-of-the-art area involving intermediates as well future challenges and opportunities.

Язык: Английский

Процитировано

118
Enantioselective C(sp3)–H Functionalization of Oxacycles via Photo-HAT/Nickel Dual Catalysis DOI
Sheng Xu, Yuanyuan Ping, Wei Li

и другие.

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(9), С. 5231 - 5241

Опубликована: Фев. 22, 2023

The selective functionalization of ubiquitous but inert C-H bonds is highly appealing in synthetic chemistry, the direct transformation hydrocarbons lacking directing groups into high-value chiral molecules remains a formidable challenge. Herein, we develop an enantioselective C(sp3)-H undirected oxacycles via photo-HAT/nickel dual catalysis. This protocol provides practical platform for rapid construction and enantiomerically enriched directly from simple abundant hydrocarbon feedstocks. utility this strategy further demonstrated late-stage natural products synthesis many pharmaceutically relevant molecules. Experimental density functional theory calculation studies provide detailed insights mechanism origin enantioselectivity asymmetric functionalization.

Язык: Английский

Процитировано

46
A Broad‐Spectrum Catalytic Amidation of Sulfonyl Fluorides and Fluorosulfates** DOI
Mingjie Wei,

Dacheng Liang,

Xiaohui Cao

и другие.

Angewandte Chemie International Edition, Год журнала: 2020, Номер 60(13), С. 7397 - 7404

Опубликована: Дек. 18, 2020

Abstract A broad‐spectrum, catalytic method has been developed for the synthesis of sulfonamides and sulfamates. With activation by combination a amount 1‐hydroxybenzotriazole (HOBt) silicon additives, amidations sulfonyl fluorides fluorosulfates proceeded smoothly excellent yields were generally obtained (87–99 %). Noticeably, this protocol is particularly efficient sterically hindered substrates. Catalyst loading low only 0.02 mol % catalyst required multidecagram‐scale an amantadine derivative. In addition, potential in medicinal chemistry demonstrated marketed drug Fedratinib via key intermediate fluoride 13 . Since large number amines are commercially available, route provides facile entry to access analogues biological screening.

Язык: Английский

Процитировано

79
Thioether-Directed NiH-Catalyzed Remote γ-C(sp3)–H Hydroamidation of Alkenes by 1,4,2-Dioxazol-5-ones DOI
Bingnan Du, Yuxin Ouyang,

Qishu Chen

и другие.

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(37), С. 14962 - 14968

Опубликована: Сен. 8, 2021

A NiH-catalyzed thioether-directed cyclometalation strategy is developed to enable remote methylene C–H bond amidation of unactivated alkenes. Due the preference for five-membered nickelacycle formation, chain-walking isomerization initiated by NiH insertion an alkene can be terminated at γ-methylene site from moiety. By employing 2,9-dibutyl-1,10-phenanthroline (L4) as ligand and dioxazolones reagent, occurs γ-C(sp3)–H bonds afford amide products in up 90% yield (>40 examples) with remarkable regioselectivity (up 24:1 rr).

Язык: Английский

Процитировано

79
Unravelling nitrene chemistry from acyclic precursors: recent advances and challenges DOI
Yuchao Wang, Xiaojing Lai, Keke Huang

и другие.

Organic Chemistry Frontiers, Год журнала: 2021, Номер 8(7), С. 1677 - 1693

Опубликована: Янв. 1, 2021

Recent advances in nitrene chemistry from acyclic precursors are reviewed this paper.

Язык: Английский

Процитировано

70
Dirhodium(II,II) Paddlewheel Complexes DOI
Radim Hrdina

European Journal of Inorganic Chemistry, Год журнала: 2021, Номер 2021(6), С. 501 - 528

Опубликована: Янв. 7, 2021

Abstract This minireview summarizes synthetic approaches towards homoleptic dirhodium(II,II) paddlewheel complexes with the general formula Rh 2 A 4 . These have found numerous applications in a wide range of chemical research and industry as catalysts, detectors, enzymatic inhibitors or building blocks for molecular scaffolds. In organic synthesis they are commonly used to transfer electron‐deficient species, act Lewis acids activate unsaturated bonds, serve hydrogenation catalysts participate oxidation/reduction processes. Dirhodium composed Rh‐Rh backbone four bridging anions, which surround core. According application, electrochemical potential atom can be modulated, geometry physical properties metal complex. prepared one step from basic inorganic precursors by post‐functionalization structures.

Язык: Английский

Процитировано

61