Lewis Acid‐Catalyzed Unusual (4+3) Annulation of para‐Quinone Methides with Bicyclobutanes: Access to Oxabicyclo[4.1.1] octanes DOI

Shiksha Deswal,

Avishek Guin, Akkattu T. Biju

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(48)

Published: Aug. 22, 2024

Abstract Over the past few years, there has been a surge of interest in chemistry bicyclobutanes (BCBs). Although BCBs have used to synthesize bicyclo[2.1.1]hexanes and bicyclo[3.1.1]heptanes, synthesis bicyclo[4.1.1]octanes remained elusive. Herein, we report first Lewis acid‐catalyzed unexpected (4+3) annulation para ‐quinonemethides ( p ‐QMs) with allowing oxabicyclo[4.1.1]octanes proceeding under mild conditions. With 5 mol % Bi(OTf) 3 , reaction afforded annulated product high regioselectivity good functional group compatibility via simultaneous acid activation ‐QMs. The is likely initiated by 1,6‐addition activated ‐QMs followed C2‐selective intramolecular addition phenol moiety generated cyclobutyl cation intermediate. Moreover, detailed mechanistic studies provided insight into mechanism reaction.

Language: Английский

Three-dimensional saturated C(sp3)-rich bioisosteres for benzene DOI
Jet Tsien, Chao Hu, Rohan R. Merchant

et al.

Nature Reviews Chemistry, Journal Year: 2024, Volume and Issue: 8(8), P. 605 - 627

Published: July 9, 2024

Language: Английский

Citations

45
Synthesis of Azabicyclo[3.1.1]heptenes Enabled by Catalyst-Controlled Annulations of Bicyclo[1.1.0]butanes with Vinyl Azides DOI

Zhongren Lin,

Haosong Ren,

Xinbo Lin

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(27), P. 18565 - 18575

Published: June 27, 2024

Bridged bicyclic scaffolds are emerging bioisosteres of planar aromatic rings under the concept "escape from flatland". However, adopting this into exploration pyridines remains elusive due to challenge incorporating a N atom such bridged structures. Herein, we report practical routes for divergent synthesis 2- and 3-azabicyclo[3.1.1]heptenes (aza-BCHepes) as potential readily accessible vinyl azides bicyclo[1.1.0]butanes (BCBs) via two distinct catalytic annulations. The reactivity tailored with BCBs is key achieving transformations. Ti

Language: Английский

Citations

41
Catalytic Asymmetric Construction of Chiral Polysubstituted 3-Azabicyclo[3.1.1]heptanes by Copper-Catalyzed Stereoselective Formal [4π+2σ] Cycloaddition DOI

Xunhua Wang,

Rongkai Gao,

Xiaoxun Li

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(30), P. 21069 - 21077

Published: July 16, 2024

The direct construction of bioisosteric compounds enriched in C

Language: Английский

Citations

33
Lewis Acid Catalyzed Cycloaddition of Bicyclobutanes with Ynamides for the Synthesis of Polysubstituted 2‐Amino‐bicyclo[2.1.1]hexenes DOI
Qianqian Hu, Liuyang Wang, Xing‐Hao Chen

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(32)

Published: May 24, 2024

Abstract Synthesis of bicyclic scaffolds has gained significant attention in drug discovery due to their potential mimic benzene bioisosteres. Here, we present a mild and scalable Sc(OTf) 3 ‐catalyzed [3+2] cycloaddition bicyclo[1.1.0]butanes (BCBs) with ynamides, yielding diverse array polysubstituted 2‐amino‐bicyclo[2.1.1]hexenes good excellent yields. These products offer valuable starting materials for the construction novel functionalized bicyclo[1.1.0]butanes. Preliminary mechanistic studies indicate that reaction involves nucleophilic addition ynamides bicyclo[1.1.0]butanes, followed by an intramolecular cyclization situ generated enolate keteniminium ion. We expect these findings will encourage utilization complex bioisosteres foster further investigation into BCB‐based chemistry.

Language: Английский

Citations

25
Palladium-catalyzed decarboxylative (4 + 3) cycloadditions of bicyclobutanes with 2-alkylidenetrimethylene carbonates for the synthesis of 2-oxabicyclo[4.1.1]octanes DOI Creative Commons

X. N. Gao,

Lei Tang, Xu Zhang

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(34), P. 13942 - 13948

Published: Jan. 1, 2024

While cycloaddition reactions of bicyclobutanes (BCBs) have emerged as a potent method for synthesizing (hetero-)bicyclo[

Language: Английский

Citations

24
Enantioselective formal (3 + 3) cycloaddition of bicyclobutanes with nitrones enabled by asymmetric Lewis acid catalysis DOI Creative Commons
Wen‐Biao Wu, Bing Xu, Xue-Chun Yang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 12, 2024

Language: Английский

Citations

23
Copper-Catalyzed Enantioselective [4π + 2σ] Cycloaddition of Bicyclobutanes with Nitrones DOI

Xuan-Ge Zhang,

Zi-Yang Zhou,

Jiaxin Li

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 25, 2024

The selective construction of bridged bicyclic scaffolds has garnered increasing attention because their extensive use as saturated bioisosteres arene in pharmaceutical industry. However, sharp contrast to racemic counterparts, assembling chiral structures an enantioselective and regioselective manner remains challenging. Herein, we describe our protocol for constructing 2-oxa-3-azabicyclo[3.1.1]heptanes (BCHeps) by [4π + 2σ] cycloadditions bicyclo[1.1.0]butanes (BCBs) nitrones taking advantage a copper(II) complex Lewis acid catalyst. This method features mild conditions, good functional group tolerance, high yield (up 99%), excellent enantioselectivity 99% ee). Density theory (DFT) calculation elucidates the origin reaction's mechanism BCB activation Cu(II) complex.

Language: Английский

Citations

20
Facile access to bicyclo[2.1.1]hexanes by Lewis acid-catalyzed formal cycloaddition between silyl enol ethers and bicyclo[1.1.0]butanes DOI Creative Commons

Sai Hu,

Yuming Pan,

Dongshun Ni

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 20, 2024

Abstract Saturated three-dimensional carbocycles have gained increasing prominence in synthetic and medicinal chemistry. In particular, bicyclo[2.1.1]hexanes (BCHs) been identified as the molecular replacement for benzenes. Here, we present facile access to a variety of BCHs via stepwise two-electron formal (3 + 2) cycloaddition between silyl enol ethers bicyclo[1.1.0]butanes (BCBs) under Lewis acid catalysis. The reaction features wide functional group tolerance ethers, allowing efficient construction two vicinal quaternary carbon centers silyl-protected tertiary alcohol unit streamlined fashion. Interestingly, with conjugated dienol can provide bicyclo[4.1.1]octanes (BCOs) equipped that facilitate further transformation. utilities this methodology are demonstrated by late-stage modification natural products, transformations units on bicyclo[2.1.1]hexane frameworks, derivatization bicyclo[4.1.1]octanes, delivering functionalized bicycles traditionally inaccessible.

Language: Английский

Citations

17
Enantioselective synthesis of 2-substituted bicyclo[1.1.1]pentanes via sequential asymmetric imine addition of bicyclo[1.1.0]butanes and skeletal editing DOI

Jinteng Che,

Wei‐Yi Ding, Hongbo Zhang

et al.

Nature Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Language: Английский

Citations

7
Silver-mediated formal [4π + 2σ] cycloaddition reactions of bicyclobutanes with nitrile imines: access to 2,3-diazobicyclo[3.1.1]heptenes DOI Creative Commons

Huijuan Liao,

Jianyang Dong,

Xuechen Zhou

et al.

Chemical Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

We disclose a method for silver-enabled formal [4π + 2 σ ] cycloaddition reactions between bicyclobutanes and nitrile imines (generated from hydrazonyl chlorides) to furnish diverse array of 2,3-diazo-BCHepes.

Language: Английский

Citations

2