Difunctionalization of C–C σ-Bonds Enabled by the Reaction of Bicyclo[1.1.0]butyl Boronate Complexes with Electrophiles: Reaction Development, Scope, and Stereochemical Origins DOI
Steven H. Bennett, Alexander Fawcett, Elliott H. Denton

et al.

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(39), P. 16766 - 16775

Published: Sept. 4, 2020

Difunctionalization reactions of C–C σ-bonds have the potential to streamline access molecules that would otherwise be difficult prepare. However, development such is challenging because are typically unreactive. Exploiting high ring-strain energy polycyclic carbocycles a common strategy weaken and facilitate reaction σ-bonds, but there limited examples highly strained being used in difunctionalization reactions. We demonstrate bicyclo[1.1.0]butyl boronate complexes (strain ca. 65 kcal/mol), which were prepared by reacting boronic esters with lithium, react electrophiles achieve diastereoselective central σ-bond unit. The shows broad substrate scope, range different successfully employed form diverse set 1,1,3-trisubstituted cyclobutanes (>50 examples) diastereoselectivity. diastereoselectivity observed has been rationalized based on combination experimental data DFT calculations, suggests separate concerted stepwise mechanisms operating, depending upon migrating substituent electrophile used.

Language: Английский

Intermolecular [2π+2σ]-photocycloaddition enabled by triplet energy transfer DOI

Roman Kleinmans,

Tobias Pinkert,

Subhabrata Dutta

et al.

Nature, Journal Year: 2022, Volume and Issue: 605(7910), P. 477 - 482

Published: March 21, 2022

Language: Английский

Citations

262
Reactions of organoboron compounds enabled by catalyst-promoted metalate shifts DOI

Sheila Namirembe,

James P. Morken

Chemical Society Reviews, Journal Year: 2019, Volume and Issue: 48(13), P. 3464 - 3474

Published: Jan. 1, 2019

This tutorial review describes recent developments in catalytic reaction design that involve catalyst-promoted 1,2-metalate shifts as a critical part of the mechanism.

Language: Английский

Citations

215
Gold-Catalyzed Synthesis of Small Rings DOI Creative Commons
Mauro Mato, Allegra Franchino, Cristina García‐Morales

et al.

Chemical Reviews, Journal Year: 2020, Volume and Issue: 121(14), P. 8613 - 8684

Published: Nov. 2, 2020

Three- and four-membered rings, widespread motifs in nature medicinal chemistry, have fascinated chemists ever since their discovery. However, due to energetic considerations, small rings are often difficult assemble. In this regard, homogeneous gold catalysis has emerged as a powerful tool construct these highly strained carbocycles. This review aims provide comprehensive summary of all the major advances discoveries made gold-catalyzed synthesis cyclopropanes, cyclopropenes, cyclobutanes, cyclobutenes, corresponding heterocyclic or heterosubstituted analogs.

Language: Английский

Citations

187
Strain release – an old tool for new transformations DOI
Joanna Turkowska, Jakub Durka, Dorota Gryko

et al.

Chemical Communications, Journal Year: 2020, Volume and Issue: 56(43), P. 5718 - 5734

Published: Jan. 1, 2020

This Feature Article provides an overview of research advances in the chemistry spring-loaded molecules, focusing mainly on strain-release transformations.

Language: Английский

Citations

162
Radical Addition to Strained σ-Bonds Enables the Stereocontrolled Synthesis of Cyclobutyl Boronic Esters DOI
Mattia Silvi, Varinder K. Aggarwal

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(24), P. 9511 - 9515

Published: May 29, 2019

While radical additions to π-bonds are well established, σ-bonds far less explored. We have found that electron deficient radicals derived from alkyl iodides under visible light irradiation add the central strained bond of bicyclobutyl (BCB)-boronate complexes and lead 1,3-alkyl disubstituted cyclobutyl boronic esters in high yields, with full stereospecificity levels stereoselectivity. Novel cyclobutyl-substituted structures, including peptide steroid ester derivatives can be accessed. Additionally, although use electron-rich as precursors was ineffective, an alternative route involving alkylsulfonylation BCB-boronate followed by reductive desulfonylation provided access simple substituted cyclobutane products.

Language: Английский

Citations

158
Bicyclobutanes: from curiosities to versatile reagents and covalent warheads DOI Creative Commons
Christopher B. Kelly, John A. Milligan, Leon J. Tilley

et al.

Chemical Science, Journal Year: 2022, Volume and Issue: 13(40), P. 11721 - 11737

Published: Jan. 1, 2022

A flurry of reports for preparing, functionalizing, and using bicyclo[1.1.0]butanes (BCBs) have positioned them to be powerful synthons with numerous applications. This review discusses the recent developments regarding this strained carbocycle.

Language: Английский

Citations

157
Bicyclobutanes as unusual building blocks for complexity generation in organic synthesis DOI Creative Commons
Maxim Golfmann, Johannes C. L. Walker

Communications Chemistry, Journal Year: 2023, Volume and Issue: 6(1)

Published: Jan. 12, 2023

Abstract Bicyclobutanes are among the most highly strained isolable organic compounds and their associated low activation barriers to reactivity make them intriguing building-blocks in chemistry. In recent years, numerous creative synthetic strategies exploiting heightened have been presented these discoveries often gone hand-in-hand with development of more practical routes for synthesis. Their proclivity as strain-release reagents through weak central C–C bond has harnessed a variety addition, rearrangement insertion reactions, providing rapid access rich tapestry complex molecular scaffolds. This review will provide an overview different options available bicyclobutane synthesis, main classes that can be prepared from bicyclobutanes, modes used.

Language: Английский

Citations

147
Beyond Bioisosteres: Divergent Synthesis of Azabicyclohexanes and Cyclobutenyl Amines from Bicyclobutanes** DOI

Kushal Dhake,

Kyla Woelk,

Joseph Becica

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(27)

Published: April 20, 2022

The development of two divergent and complementary Lewis acid catalyzed additions bicyclobutanes to imines is described. Microscale high-throughput experimentation was integral the discovery optimization both reactions. N-arylimines undergo formal (3+2) cycloaddition with yield azabicyclo[2.1.1]hexanes in a single step; contrast, N-alkylimines an addition/elimination sequence generate cyclobutenyl methanamine products high diastereoselectivity. These new contain variety synthetic handles for further elaboration, including many functional groups relevant pharmaceutical synthesis. reactivity observed attributed differences basicity nucleophilicity nitrogen atom common carbocation intermediate, leading either nucleophilic attack (N-aryl) or E1 elimination (N-alkyl).

Language: Английский

Citations

143
Photochemical Intermolecular [3σ + 2σ]-Cycloaddition for the Construction of Aminobicyclo[3.1.1]heptanes DOI
Yongxiang Zheng, Weichen Huang,

Roshan K. Dhungana

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(51), P. 23685 - 23690

Published: Dec. 16, 2022

The development of synthetic strategies for the preparation bioisosteric compounds is a demanding undertaking in medicinal chemistry. Numerous have been developed synthesis bicyclo[1.1.1]pentanes (BCPs), bridge-substituted BCPs, and bicyclo[2.1.1]hexanes. However, progress on bicyclo[3.1.1]heptanes, which serve as meta-substituted arene bioisosteres, has not previously explored. Herein, we disclose first photoinduced [3σ + 2σ] cycloaddition trisubstituted bicyclo[3.1.1]heptanes using bicyclo[1.1.0]butanes cyclopropylamines. This transformation only uses mild operationally simple conditions but also provides unique bioisosteres. applicability this method showcased by derivatization reactions.

Language: Английский

Citations

141
ortho-Selective Dearomative [2π + 2σ] Photocycloadditions of Bicyclic Aza-Arenes DOI

Roman Kleinmans,

Subhabrata Dutta,

Kristers Ozols

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(22), P. 12324 - 12332

Published: May 26, 2023

Dearomative photocycloadditions are valuable chemical transformations, serving as an efficient platform to create three-dimensional molecular complexity. However, the photolability of original addition product especially within context ortho cycloadditions often causes undesired consecutive rearrangements, rendering these cycloadducts elusive. Herein, we report ortho-selective intermolecular photocycloaddition bicyclic aza-arenes including (iso)quinolines, quinazolines, and quinoxalines by utilizing a strain-release approach. With bicyclo[1.1.0]butanes coupling partners, this dearomative [2π + 2σ] cycloaddition enables straightforward construction C(sp3)-rich bicyclo[2.1.1]hexanes directly connected N-heteroarenes. Photophysical experiments DFT calculations revealed origin selectivity indicate that, in originally proposed energy transfer or direct excitation pathways, chain reaction mechanism is operative depending on conditions.

Language: Английский

Citations

127