Divergent Enantioselective Access to Diverse Chiral Compounds from Bicyclo[1.1.0]butanes and α,β-Unsaturated Ketones under Catalyst Control DOI
Jinwook Jeong, Shi Cao, Hyung‐Joon Kang

et al.

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

Published: Sept. 30, 2024

Achieving structural and stereogenic diversity from the same starting materials remains a fundamental challenge in organic synthesis, requiring precise control over selectivity. Here, we report divergent catalytic methods that selectively yield either cycloaddition or addition/elimination products bicyclo[1.1.0]butanes α,β-unsaturated ketones. By employing chiral Lewis acid Brønsted catalysts, achieved excellent regio-, diastereo-, enantioselectivity across all three distinct transformations, affording diverse array of synthetically valuable bicyclo[2.1.1]hexanes cyclobutenes. The outcomes are controlled by differential activation substrates specific catalyst with reaction conditions dictating pathway This strategy demonstrates power catalysis creating molecular complexity diversity, offering tool for synthesis enantioenriched building blocks.

Language: Английский

Hantzsch Esters Enabled [2π+2σ] Cycloadditions of Bicyclo [1.1.0] butanes and Alkenes under Photo Conditions DOI

Huaipu Yan,

Yonghong Liu, Xiao Feng

et al.

Organic Letters, Journal Year: 2023, Volume and Issue: 25(45), P. 8116 - 8120

Published: Nov. 8, 2023

Hantzsch esters (HEs) are widely recognized as sources of hydride ions (H-) and sacrificial electron donors in their ground state. Here, we report the application HE a mediator [2π+2σ] cycloaddition bicyclo[1.1.0]butanes (BCBs) with alkenes under photo conditions. Through this strategy, various substituted bicyclo[2.1.1]hexanes can be efficiently prepared.

Language: Английский

Citations

51
Palladium-Catalyzed Ligand-Controlled Switchable Hetero-(5 + 3)/Enantioselective [2σ+2σ] Cycloadditions of Bicyclobutanes with Vinyl Oxiranes DOI
Jin‐Lan Zhou, Yuanjiu Xiao,

Linke He

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(29), P. 19621 - 19628

Published: May 13, 2024

For nearly 60 years, significant research efforts have been focused on developing strategies for the cycloaddition of bicyclobutanes (BCBs). However, higher-order and catalytic asymmetric BCBs long-standing formidable challenges. Here, we report Pd-catalyzed ligand-controlled, tunable cycloadditions divergent synthesis bridged bicyclic frameworks. The dppb ligand facilitates formal (5+3) vinyl oxiranes, yielding valuable eight-membered ethers with scaffolds in 100% regioselectivity. Cy-DPEphos promotes selective hetero-[2σ+2σ] to access pharmacologically important 2-oxabicyclo[3.1.1]heptane (O-BCHeps). Furthermore, corresponding O-BCHeps 94–99% ee has achieved using chiral (S)-DTBM-Segphos, representing first cross-dimerization two strained rings. obtained are promising bioisosteres ortho-substituted benzenes.

Language: Английский

Citations

48
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
Silver‐Enabled Cycloaddition of Bicyclobutanes with Isocyanides for the Synthesis of Polysubstituted 3‐Azabicyclo[3.1.1]heptanes DOI
Yujie Liang, Ronewa Nematswerani, Constantin G. Daniliuc

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(21)

Published: March 5, 2024

Abstract Synthesis of bicyclic scaffolds has emerged as an important research topic in modern drug development because they can serve saturated bioisosters to enhance the physicochemical properties and metabolic profiles candidates. Here we report a remarkably simple silver‐enabled strategy access polysubstituted 3‐azabicyclo[3.1.1]heptanes single operation from readily accessible bicyclobutanes (BCBs) isocyanides. The process is proposed involve formal (3+3)/(3+2)/retro‐(3+2) cycloaddition sequence. This novel protocol allows for rapid generation molecular complexity starting materials, products be easily derivatized, further enriching BCB chemistry growing set valuable sp 3 ‐rich building blocks.

Language: Английский

Citations

44
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

42
Switching between the [2π+2σ] and Hetero‐[4π+2σ] Cycloaddition Reactivity of Bicyclobutanes with Lewis Acid Catalysts Enables the Synthesis of Spirocycles and Bridged Heterocycles DOI
Jijie Wang, Lei Tang, Yuanjiu Xiao

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(29)

Published: May 11, 2024

Abstract The exploration of the complex chemical diversity bicyclo[n.1.1]alkanes and their use as benzene bioisosteres has garnered significant attention over past two decades. Regiodivergent syntheses thiabicyclo[4.1.1]octanes (S‐BCOs) highly substituted bicyclo[2.1.1]hexanes (BCHs) using a Lewis acid‐catalyzed formal cycloaddition bicyclobutanes (BCBs) 3‐benzylideneindoline‐2‐thione derivatives have been established. first hetero‐(4+3) BCBs, catalyzed by Zn(OTf) 2 , was achieved with broad substrate scope under mild conditions. In contrast, less electrophilic BCB ester undergoes Sc(OTf) 3 ‐catalyzed [2π+2σ] reaction 1,1,2‐trisubstituted alkenes, yielding BCHs spirocyclic quaternary carbon center. Control experiments preliminary theoretical calculations suggest that diastereoselective product formation may involve concerted between zwitterionic intermediate E ‐1,1,2‐trisubstituted alkenes. Additionally, nucleophilic ring‐opening mechanism.

Language: Английский

Citations

40
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

36
Ti-Catalyzed Formal [2π + 2σ] Cycloadditions of Bicyclo[1.1.0]butanes with 2-Azadienes to Access Aminobicyclo[2.1.1]hexanes DOI

Haosong Ren,

Tianxiang Li,

Jinping Xing

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(8), P. 1745 - 1750

Published: Feb. 20, 2024

Saturated bicyclic amines are increasingly targeted to the pharmaceutical industry as sp3-rich bioisosteres of anilines. Numerous strategies have been established for preparation bridgehead aminobicyclics. However, methods assemble bridge-amino hydrocarbon skeleton, which serves a meta-substituted arene bioisostere, limited. Herein, general approach access 2-aminobicyclo[2.1.1]hexanes (aminoBCHs) by titanium-catalyzed formal [2π + 2σ] cycloaddition bicyclo[1.1.0]butanes and 2-azadienes was developed. Simple derivatization aminoBCHs leads various medicinally agrochemically important analogues.

Language: Английский

Citations

34
Bicyclo[1.1.0]butyl Radical Cations: Synthesis and Application to [2π + 2σ] Cycloaddition Reactions DOI Creative Commons
Jasper L. Tyler, Felix Schäfer, Huiling Shao

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(23), P. 16237 - 16247

Published: May 29, 2024

As the chemistry that surrounds field of strained hydrocarbons, such as bicyclo[1.1.0]butane, continues to expand, it becomes increasingly advantageous develop alternative reactivity modes harness their unique properties access new regions chemical space. Herein, we report use photoredox catalysis promote single-electron oxidation bicyclo[1.1.0]butanes. The synthetic utility resulting radical cations is highlighted by ability undergo highly regio- and diastereoselective [2π + 2σ] cycloaddition reactions. most notable feature this transformation breadth alkene classes can be employed, including nonactivated alkenes, which have so far been elusive for previous strategies. A rigorous mechanistic investigation, in conjunction with DFT computation, was undertaken order better understand physical nature bicyclo[1.1.0]butyl thus provides a platform from further studies into applications these intermediates built upon.

Language: Английский

Citations

33
Reaction Paradigms that Leverage Cycloaddition and Ring Strain to Construction Bicyclic Aryl Bioisosteres from Bicyclo[1.1.0]butanes DOI

Stephen J. Sujansky,

Xiaoshen Ma

Asian Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 13(5)

Published: Feb. 21, 2024

Abstract Within a medicinal chemist's toolbox, one of the most effective strategies to improve overall properties biologically active compound is bioisosteric replacement. Ever since first example replacing benzene with bicyclo[1.1.1]pentane (BCP) group was published in late 1990s, [1] chemistry community has continually been expanding scope such phenyl replacements. Recent interest from academia focused on novel synthetic access C( sp 3 )‐rich bicyclic hydrocarbons expanded ring sizes. Herein, we summarize some these transformations and reveal that rely strain releasing cycloadditions bicyclo[1.1.0]butane (BCB) bicyclo[2.1.0]pentane (housane). We have organized this review based mechanism release strategies, namely, carbene cycloadditions, energy transfer photocatalyzed electron catalyzed polar cycloadditions.

Language: Английский

Citations

30