Late-stage diversification of indole skeletons through nitrogen atom insertion

Science, Год журнала: 2022, Номер 377(6610), С. 1104 - 1109

Опубликована: Сен. 1, 2022

Compared with peripheral late-stage transformations mainly focusing on carbon-hydrogen functionalizations, reliable strategies to directly edit the core skeleton of pharmaceutical lead compounds still remain scarce despite recent flurry activity in this area. Herein, we report skeletal editing indoles through nitrogen atom insertion, accessing corresponding quinazoline or quinoxaline bioisosteres by trapping an electrophilic nitrene species generated from ammonium carbamate and hypervalent iodine. This reactivity relies strategic use a silyl group as labile protecting that can facilitate subsequent product release. The utility highly functional group-compatible methodology context several commercial drugs is demonstrated.

Язык: Английский

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Stereoselective Synthesis of Cyclobutanes by Contraction of Pyrrolidines

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(45), С. 18864 - 18870

Опубликована: Ноя. 8, 2021

Here we report a contractive synthesis of multisubstituted cyclobutanes containing multiple stereocenters from readily accessible pyrrolidines using iodonitrene chemistry. Mediated by nitrogen extrusion process, the stereospecific involves radical pathway. Unprecedented unsymmetrical spirocyclobutanes were prepared successfully, and concise, formal cytotoxic natural product piperarborenine B is reported.

Язык: Английский

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Energy transfer-enabled unsymmetrical diamination using bifunctional nitrogen-radical precursors

Nature Catalysis, Год журнала: 2022, Номер 5(12), С. 1120 - 1130

Опубликована: Дек. 8, 2022

Язык: Английский

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Regioselective Access to Vicinal Diamines by Metal‐Free Photosensitized Amidylimination of Alkenes with Oxime Esters

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(44)

Опубликована: Сен. 9, 2022

A metal-free photosensitized protocol for regioselective diamination of alkene feedstocks over a single step was developed based on the rationally designed bifunctional reagent, thus affording range differentially protected 1,2-diamines in moderate to high yields. Mechanistic studies reveal that reaction is initiated with triplet-triplet energy transfer between thioxanthone catalyst and followed by fragmentation simultaneously generate long-lived iminyl radical transient amidyl radical. The excellent regioselectivity presumably stems from large reactivity difference two different N-centered species. This characterized regioselectivity, broad functional group tolerance, mild conditions, which would enrich diversity versatility facilitate diversity-oriented synthesis 1,2-diamine-containing complex molecule scaffolds.

Язык: Английский

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The advent of electrophilic hydroxylamine-derived reagents for the direct preparation of unprotected amines

Chemical Communications, Год журнала: 2022, Номер 58(72), С. 9991 - 10003

Опубликована: Янв. 1, 2022

Electrophilic aminating reagents have seen a renaissance in recent years as effective nitrogen sources for the synthesis of unprotected amino functionalities.

Язык: Английский

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Selective Difunctionalization of Unactivated Aliphatic Alkenes Enabled by a Metal–Metallaaromatic Catalytic System

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(5), С. 2301 - 2310

Опубликована: Янв. 25, 2022

The design of organometallic catalysts is crucial in the development catalytic reactions. Herein, we describe a heterometallic [Os-Cu] complex with characteristics bimetallics, metallaaromatics, and pincer complexes. This serves as highly effective catalyst for selective amino- oxyselenation unactivated alkenes. More than 80 examples including challenging substrates unsymmetric aliphatic alkenes amine-based nucleophiles such reactions are provided. These produce 1,2-difunctionalized products good yields high levels chemo-, regio-, stereoselectivity. Our studies revealed following: (i) usually inert osmium center activates N- or O-centered nucleophiles. (ii) copper–osmium bonding its cooperative effects play essential roles control selectivity by bringing reaction components into close proximity. (iii) metallaaromatic moiety helps to stabilize intermediate. findings provide versatile platform based on metal–metallaaromatic that have not been attained previously bimetallic

Язык: Английский

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Reductive Coupling of Nitroarenes and HCHO for General Synthesis of Functional Ethane-1,2-diamines by a Cobalt Single-Atom Catalyst

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(31), С. 17329 - 17336

Опубликована: Июль 7, 2023

Despite the extensive applications, selective and diverse access to N,N'-diarylethane-1,2-diamines remains, date, a challenge. Here, by developing bifunctional cobalt single-atom catalyst (CoSA-N/NC), we present general method for direct synthesis of such compounds via reductive coupling cheap abundant nitroarenes formaldehyde, featuring good substrate functionality compatibility, an easily accessible base metal with excellent reusability, high step atom efficiency. Mechanistic studies reveal that N-anchored single atoms (CoN4) serve as catalytically active sites reduction processes, N-doped carbon support enriches HCHO timely trap in situ formed hydroxyamines affords requisite nitrones under weak alkaline conditions, subsequent inverse electron demand 1,3-dipolar cycloaddition imines followed hydrodeoxygenation cycloadducts furnishes products. In this work, concept catalyst-controlled nitroarene create specific building blocks is anticipated develop more useful chemical transformations.

Язык: Английский

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Photoredox Catalytic Three-Component Amidoazidation of 1,3-Dienes

ACS Catalysis, Год журнала: 2021, Номер 11(17), С. 10871 - 10877

Опубликована: Авг. 17, 2021

In spite of the obvious synthetic potential functionalized allylic azides, only limited routes have been developed. We report herein a three-component 1,2-amidoazidation 1,3-dienes. presence fac-Ir(ppy)3 under blue LED irradiation, reaction 1-aryl substituted 1,3-dienes with N-amidopyridinium salt and trimethylsilyl azide (TMSN3) affords exclusively products. The 1-alkyl counterparts undergo same moderate to high 1,2- vs 1,4-selectivity. Reduction this mixture PPh3 dynamic kinetic conditions enriches significantly one two isomers thanks facile 1,3-azide shift (Winstein rearrangement) allyl azides.

Язык: Английский

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Chiral Hypervalent Bromine(III) (Bromonium Salt): Hydrogen- and Halogen-Bonding Bifunctional Asymmetric Catalysis by Diaryl-λ³-bromanes

ACS Catalysis, Год журнала: 2021, Номер 11(21), С. 13028 - 13033

Опубликована: Окт. 13, 2021

Bromonium salts, which are hypervalent bromine reagents, have been explored as being strong electrophiles owing to their extremely high nucleofugalities. Only one example of catalytic application has reported by our group; however, chiral versions not yet researched. Halogen-bonding (XB) widely applied in chemistry; its successful highly enantioselective Lewis acid catalysis achieved. Herein, we report the design and development cyclic diarylbromonium salts. These catalysts enabled a XB catalysis, giving products with up 96% ee.

Язык: Английский

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From Serendipity to Rational Design: Heteroleptic Dirhodium Amidate Complexes for Diastereodivergent Asymmetric Cyclopropanation

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(16), С. 7465 - 7478

Опубликована: Апрель 14, 2022

A heteroleptic dirhodium paddlewheel complex comprising three chiral carboxylate ligands and one achiral acetamidate ligand has recently been found to be uniquely effective in catalyzing the asymmetric cyclopropanation of olefins with α-stannylated (silylated germylated) α-diazoacetate derivatives. number control experiments combination detailed computational studies provide compelling evidence that an interligand hydrogen bond between −NH group amidate ester carbonyl reactive rhodium carbene intermediate plays a quintessential role stereodetermining transition state. The penalty for distorting this array outweighs steric arguments renders two four conceivable transitions states unviable. Based on mechanistic insight, design parent catalyst is revisited herein: placement appropriate peripheral substituents allows high levels diastereocontrol imposed upon cyclopropanation, which original lacks. Because new complexes allow either trans- or cis-configured stannylated cyclopropanes made selectively excellent optical purity, transformation also marks rare case diastereodivergent catalysis. products are amenable stereospecific cross coupling aryl halides alkenyl triflates; these transformations appear first examples formation stereogenic quaternary carbon centers by Stille reaction; carbonylative achieved. Moreover, tin/lithium exchange affords lithium enolates, can intercepted variety electrophilic partners. virtues inherent flexibility methodology illustrated efficient synthesis salinilactones, extremely scarce bacterial metabolites signaling function involved self-regulatory growth inhibition producing strain.

Язык: Английский

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