Rapid Access to Chiral Spiro[2.3] Lactams: Stereoselective Hydroborylation and Hydrosilylation and Remote Control of Axial Chirality by Copper-Catalyzed Desymmetrization of Spirocyclopropenes

Organic Letters, Год журнала: 2024, Номер 26(9), С. 1941 - 1946

Опубликована: Фев. 28, 2024

Chiral spirocyclopropyl β-lactams are common motifs in bioactive compounds and pharmaceuticals. Here we disclose a diastereoselective enantioselective hydroborylation hydrosilylation of spirocyclopropenes, via Cu-catalyzed desymmetrization strategy, for the rapid preparation enantio-enriched β-lactams. The efficient strategy allows remote control axial chirality, offering borylated silylated products bearing central, spiro, chirality. combination multichiral elements would provide novel motif biological evaluation potential drug discovery.

Язык: Английский

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Expedient Access to Enantioenriched 1‐Azaspiro Cyclobutanones Enabled by Modified Heyns Rearrangement

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

Опубликована: Июнь 13, 2023

Leveraging the unexplored regions of chemical space, integration spirocyclic cyclobutane in a molecular scaffold opens up new vista modern drug discovery. Despite recent advancements achieving synthesis such motifs, strategies for their asymmetric construction have not been well-recognized and remain formidable challenge. Herein, first time, we demonstrated chiral Brønsted acid-catalyzed enantioselective 1-azaspiro cyclobutanone enabled by an unusual reactivity enamine that explore potentiality Heyns rearrangement upon electrophilic modification. This design strategy offers viable access to wide range containing spiroindoline spiropyrrolidine derivatives good yields with excellent stereoselectivities (up >99 % ee, >20 : 1 dr). Furthermore, practicality this methodology has shown scale-up products facile post-synthetic modifications.

Язык: Английский

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A Modular Access to 1,2‐ and 1,3‐Disubstituted Cyclobutylboronic Esters by Consecutive Radical Additions

Angewandte Chemie International Edition, Год журнала: 2021, Номер 61(3)

Опубликована: Окт. 30, 2021

A modular approach to substituted cyclobutylboronic esters is described. It proceeds by successive intermolecular radical additions of xanthates pinacolato 1-cyclobutenylboronate and bicyclo[1.1.0]but-1-ylboronate. Success hinges on tuning the stability α-boryl exploiting stabilizing influence trivalent boronic ester slightly destabilizing cyclobutane, which increases σ-character radical. Reductive removal xanthate group finally provides a range 1,2- 1,3-disubstituted esters. The contrast with cyclopropylboronic striking, since strong destabilization highly strained cyclopropane ring allows first addition take place but not second. Furthermore, adducts are geminal xanthyl that can be converted into cyclobutanones. This chemistry furnishes would quite difficult obtain otherwise thus complements existing methods.

Язык: Английский

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Photosensitized [2+2]‐Cycloadditions of Alkenylboronates and Alkenes

Angewandte Chemie, Год журнала: 2022, Номер 134(25)

Опубликована: Апрель 21, 2022

Abstract A new strategy for the synthesis of highly versatile cyclobutylboronates via photosensitized [2+2]‐cycloaddition alkenylboronates and alkenes is presented. The process mechanistically different from other processes in that energy transfer occurs with alkenylboronate as opposed to alkene. This allows an array diverse cyclobutylboronates. conversion these adducts compounds well their utility melicodenine C demonstrated.

Язык: Английский

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Boosting the Enantioselectivity of Conjugate Borylation of α,β‐Disubstituted Cyclobutenones with Monooxides of ChiralC₂‐Symmetric Bis(phosphine) Ligands

Chemistry - A European Journal, Год журнала: 2022, Номер 28(62)

Опубликована: Июль 11, 2022

Chiral bis(phosphine) monooxides (BPMOs) derived from C

Язык: Английский

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Photochemical [2+2] Cycloaddition of Alkynyl Boronates

Chemistry - A European Journal, Год журнала: 2023, Номер 29(54)

Опубликована: Июль 3, 2023

Abstract A photochemical [2+2] cycloaddition of alkynyl boronates and maleimides is reported. The developed protocol provided 35–70 % yield maleimide‐derived cyclobutenyl demonstrated wide compatibility with various functional groups. synthetic utility the prepared building blocks was for a range transformations, including Suzuki cross‐coupling, catalytic or metal‐hydride reduction, oxidation, reactions. With aryl‐substituted boronates, products double were obtained predominantly. Using protocol, cyclobutene‐derived analogue Thalidomide in one step. Mechanistic studies supported participation triplet‐excited state ground key step process.

Язык: Английский

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Photoredox cobalt-catalyzed asymmetric desymmetric reductive coupling of cyclobutenes with alkynes

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 1, 2025

Catalytic methods to couple alkynes and alkenes are highly valuable in synthetic chemistry. The cobalt-catalyzed intermolecular reductive coupling of is particularly attractive due the unique reactivity cost-effectiveness cobalt catalysts. However, enantioselective transformations this kind less developed. limited successful examples restricted use electronically biased activated olefins as partners. Herein, we report an asymmetric desymmetric unbiased succinimide-containing cyclobutenes with synthesize enantioenriched, synthetically important vinyl cyclobutanes via photoredox dual catalysis. Excellent enantioselectivities, good diastereoselectivities regioselectivities obtained. Preliminary mechanistic studies suggest that Hantzsch ester a better reducing reagent when used combination Et3N. Density functional theory calculations reveal reaction proceeds more likely through Co(III)-H migratory insertion mechanism. Here, authors internal

Язык: Английский

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Strained spiro heterocycles as potential bioisosteres: an update on the synthesis of heteroatom-containing spiro[2.3]hexanes and spiro[3.3]heptanes

Chemical Communications, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Developments in the synthesis and application of strained spiro heterocycles are discussed, given their potential as non-classical rigid three-dimensional bioisosteres drug development.

Язык: Английский

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Recent Advances in Non-Precious Metal Catalysis

Organic Process Research & Development, Год журнала: 2022, Номер 26(8), С. 2281 - 2310

Опубликована: Авг. 2, 2022

This review provides a summary of recently published developments in the field nonprecious metal catalysis (NPMC) and highlights range synthetic applications captured research between July October 2021. is an installment series on this area briefing Ni, Cu, Fe, Co catalysis. There has been evident increase publications NPMC, which indicates widespread interest among laboratories academia industry development utilization catalytic these metals.

Язык: Английский

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Catalytic asymmetric hydrometallation of cyclobutenes with salicylaldehydes

Chemical Science, Год журнала: 2021, Номер 13(1), С. 236 - 240

Опубликована: Дек. 10, 2021

Chiral, substituted cyclobutanes are common motifs in bioactive compounds and intermediates organic synthesis but few asymmetric routes for their known.

Язык: Английский

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