Copper‐Catalyzed Enantioselective Doyle–Kirmse Reaction of Azide‐Ynamides via α‐Imino Copper Carbenes

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(10)

Опубликована: Янв. 14, 2023

[2,3]-Sigmatropic rearrangement reaction involving sulfonium ylide (Doyle-Kirmse reaction) generated from metal carbenes represents one of the powerful methods for construction C(sp3 )-S and C-C bonds. Although significant advances have been achieved, asymmetric versions via generation ylides rarely reported to date, they so far limited diazo compounds as carbene precursors. Here, we describe a copper-catalyzed enantioselective Doyle-Kirmse azide-ynamide cyclization, leading practical divergent assembly an array chiral [1,4]thiazino[3,2-b]indoles bearing quaternary carbon stereocenter in generally moderate excellent yields enantioselectivities. Importantly, this protocol unique catalytic non-diazo approach unprecedented [2,3]-sigmatropic α-imino carbenes.

Язык: Английский

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Triftosylhydrazone in Single-Atom Skeletal Editing

Accounts of Chemical Research, Год журнала: 2024, Номер unknown

Опубликована: Дек. 16, 2024

ConspectusIn the past decade, single-atom skeletal editing, which involves precise insertion, deletion, or exchange of single atoms in core skeleton a molecule, has emerged as promising synthetic strategy for rapid construction diversification complex molecules without laborious de novo processes. Among them, carbene-initiated editing is particularly appealing due to ready availability and diverse reactivities carbene species. The initial endeavors modify heteroarenes through carbon-atom insertion could date back 1881, when Ciamician Denstedt described conversion pyrroles pyridines by trapping haloform-derived free carbene. Despite its potential value, general applicability this one-carbon seen limited progress poor yields harsh reaction conditions. Significant advances via were achieved only 3 years Levin, Ball, Xu, Song, Glorius, others. hallmark these approaches facile halocyclopropanation followed regioselective ring opening facilitated expulsion halide ion. Consequently, specially designed α-halocarbene precursors, such haloform derivatives, α-halodiazoacetates, chlorodiazirines, α-chlorodiazo oxime esters, can be employed achieve Ciamician–Denstedt-type editing. This not limits types functional groups installed on expansion products but also prevents their widespread adoption, especially late-stage contexts. enduring quest develop environmentally friendly versatile superior group compatibility, application diversifications investigation mechanistic insights into carbon reactions remain fundamental objective.In our over 5 years, we have developed o-trifluoromethylbenzenesulfonylhydrazones (named Triftosylhydrazones) operationally safe easily decomposable diazo surrogates explored various challenging catalytic transfer reactions. Recently, put great efforts expanding scope unlocking triftosylhydrazones precursors Since 2018, realized range acyclic 1,3-dicarbonyls with silver carbenes access 1,4-dicarbonyls, proceeding cyclopropanation/ring-opening process. Inspired results, recently demonstrated series transition-metal-catalyzed highly selective medicinally interesting like pyrroles, indoles, 1,2-diazoles carbenic insertion. We then strained three-membered nitrogen- oxygen-containing heterocycles single-carbon atoms. In Account, present an overview achievements heterocycles, organized based three situ-generated key intermediates, cyclopropane, N-ylide, O-ylide from focus scopes, features, applications. hope that Account will provide valuable contribute development new methodologies both chemistry fields.

Язык: Английский

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Catalytic enantioselective reductive Eschenmoser-Claisen rearrangements

Science, Год журнала: 2024, Номер 383(6681), С. 395 - 401

Опубликована: Янв. 25, 2024

An important challenge in enantioselective catalysis is developing strategies for the precise synthesis of neighboring congested all-carbon quaternary stereocenters. The well-defined transition states [3,3]-sigmatropic rearrangements and their underlying stereospecificity render them powerful tools such arrays. However, this type pericyclic reaction remains notoriously difficult to catalyze, especially an fashion. Herein, we describe reductive Eschenmoser-Claisen rearrangement catalyzed by chiral 1,3,2-diazaphospholene-hydrides. This developed transformation enables full control two newly formed acyclic stereogenic centers, leading amides with vicinal quaternary-tertiary or quaternary-quaternary carbon atoms.

Язык: Английский

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Gd(III)-Catalyzed Regio-, Diastereo-, and Enantioselective [4 + 2] Photocycloaddition of Naphthalene Derivatives

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(25), С. 16982 - 16989

Опубликована: Июнь 13, 2024

Catalytic asymmetric dearomatization (CADA) reactions have evolved into an efficient strategy for accessing chiral polycyclic and spirocyclic scaffolds from readily available planar aromatics. Despite the significant developments, CADA reaction of naphthalenes remains underdeveloped. Herein, we report a Gd(III)-catalyzed naphthalene with PyBox ligand via visible-light-enabled [4 + 2] cycloaddition. This features application Gd/PyBox complex, which regulates reactivity selectivity simultaneously, in excited-state catalysis. A wide range functional groups is compatible this protocol, giving highly enantioenriched bridged polycycles excellent yields (up to 96%) >20:1 chemoselectivity, dr, >99% ee). The synthetic utility demonstrated by 2 mmol scale reaction, removal directing group, diversifications products. Preliminary mechanistic experiments are performed elucidate mechanism.

Язык: Английский

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Sterically Hindered and Deconjugative α‐Regioselective Asymmetric Mannich Reaction of Meinwald Rearrangement‐Intermediate

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(13)

Опубликована: Янв. 26, 2023

Compared to γ-addition, the α-addition of α-branched β,γ-unsaturated aldehydes faces larger steric hindrance and disrupts π-π conjugation, which might be why very few examples are reported. In this article, a highly diastereo- enantioselective α-regioselective Mannich reaction isatin-derived ketimines with α-, β- or γ-branched aldehydes, generated in situ from Meinwald rearrangement vinyl epoxides, is realized by using chiral N,N'-dioxide/ScIII catalysts. A series α-quaternary allyl homoallylic alcohols vicinal multisubstituted stereocenters constructed excellent yields, good d.r. ee values. Experimental studies DFT (density functional theory) calculations reveal that large ligand Boc (tButyloxy carbonyl) protecting group imines critical factors for α-regioselectivity.

Язык: Английский

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Substituent-Controlled Regiodivergent Rearrangement of Gramine Ammonium Ylide

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

The complicated mechanism makes the regiodivergent rearrangement of ammonium ylide seem to be out reach. Herein, we reported a gramine well controlled by substituents. Density functional theory studies reveal that with more steric hindrance substituent 2-diazo-2-arylacetate goes through stepwise yield both kinetically and thermodynamically preferred [1,2]-rearrangement product. In contrast, less ethyl diazoacetate concerted generate [2,3]-rearrangement product, which is favored as result release ring strain in transition state. This study would open up avenues grasp ylide, will promote application skeletal editing synthesis complex natural products.

Язык: Английский

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Photoredox-catalyzed diastereoselective dearomative prenylation and reverse-prenylation of electron-deficient indole derivatives

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Июнь 30, 2023

Abstract Prenylated and reverse-prenylated indolines are privileged scaffolds in numerous naturally occurring indole alkaloids with a broad spectrum of important biological properties. Development straightforward stereoselective methods to enable the synthesis structurally diverse prenylated indoline derivatives is highly desirable challenging. In this context, most direct approaches achieve goal generally rely on transition-metal-catalyzed dearomative allylic alkylation electron-rich indoles. However, electron-deficient indoles much less explored, probably due their diminished nucleophilicity. Herein, photoredox-catalyzed tandem Giese radical addition/Ireland–Claisen rearrangement disclosed. Diastereoselective prenylation reverse-prenylation proceed smoothly under mild conditions. An array tertiary α-silylamines as precursors readily incorporated 2,3-disubstituted high functional compatibility excellent diastereoselectivity (>20:1 d.r.). The corresponding transformations secondary provide biologically lactam-fused one-pot synthesis. Subsequently, plausible photoredox pathway proposed based control experiments. preliminary bioactivity study reveals potential anticancer property these appealing indolines.

Язык: Английский

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Stereoselective Synthesis of Polysubstituted Conjugated Dienes Enabled by Photo‐Driven Sequential Sigmatropic Rearrangement

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(24)

Опубликована: Апрель 8, 2024

We here reported a highly stereoselective method for the synthesis of polysubstituted conjugated dienes from α-aryl α-diazo alkynyl ketones and pyrazole-substituted unsymmetric aminals under mild conditions, which was promoted by photo-irridation involved with 1,6-dipolar intermediate quadruple sigmatropic rearrangements, successfully developed. In this transformation, cleavage four bonds recombination five were implemented in one operational step. This protocol provided modular tool constructing amines, pyrazoles α-alkynyl-α-diazoketones one-pot manner. The results mechanistic investigation indicated that plausible reaction path underwent 1,6-sigmatropic rearrangement instead 1,5-sigmatropic rearrangement.

Язык: Английский

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Asymmetric Catalytic Ring‐Expansion of 3‐Methyleneazetidines with α‐Diazo Pyrazoamides towards Proline‐Derivatives

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(32)

Опубликована: Июнь 15, 2023

We realized a highly efficient formal [1,2]-sigmatropic rearrangement of ammonium ylides generated from 3-methylene-azetidines and α-diazo pyrazoamides. The employ readily available chiral cobalt(II) complex N,N'-dioxide enabled the ring-expansion azetidines, affording variety quaternary prolineamide derivatives with excellent yield (up to 99 %) enantioselectivity % ee) under mild reaction condition. For ylides, installation pyrazoamide group as masked brick build scaffolds proved successful. enantioselective ring expansion process was elucidated by DFT calculations.

Язык: Английский

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[3,3]‐Sigmatropic Rearrangements of Naphthyl 1‐Propargyl Ethers: para‐Propargylation and Catalytic Asymmetric Dearomatization

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(52)

Опубликована: Ноя. 1, 2022

The para-Claisen rearrangement of aryl 1-propargyl ethers involves two-step [3,3]-sigmatropic rearrangements and dearomatization process, which has high activation barriers is challenge. Here we discovered thermal naphthyl ethers, it enabled the formation formal para-C-H propargylation products upon rearomatization. Chirality transfer occurred if optically active propargyl were employed, leading to construction aryl/propargyl-containing stereogenic centers. Moreover, catalytic asymmetric with different substitution at para-position gave access benzocyclohexenones bearing all-carbon quaternary stereocenters. reaction was accelerated by a chiral N,N'-dioxide/Co(OTf)2 complex catalyst achieve yields (up 98 %) enantioselectivities 93 % ee). DFT calculations experimental results provided important clues clarify process as well induction remote delivery.

Язык: Английский

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