Merging Nucleophilic Phosphine Catalysis and Photocatalysis for the Rapid Assembly of 2-Oxabicyclo-[2.1.1]hexane Scaffolds from Feedstock Allyl Alcohols DOI Creative Commons
David M. Whalley, Luca Carlino, Okky Dwichandra Putra

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

The previously unreported combination of nucleophilic phosphine catalysis and energy transfer allows for the rapid construction structurally distinct 2-oxabicyclo[2.1.1]hexanes (2-oxa-BCH) from readily available building blocks with high atom economy. Previous multistep routes to these important phenyl ring bioisosteres have largely depended on use bespoke strain-release agents or multiple post-functionalisation reactions access structural diversity scaffold. In contrast, this cascade reaction medicinal chemist exploit breadth commercial allyl alcohols synthesise systematically diverse 2-oxa-BCH architectures. Using a polar radical disconnections in same flask, every position scaffold can be substituted useful functional handles such as protected amines, esters alcohols, well arenes alkyl groups. Cyclic even employed yield single diastereomers sp

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
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 [2π + 2σ] cycloaddition of bicyclobutanes with imines: An efficient approach to chiral 2-aza-bicyclo[2.1.1]hexanes DOI

Xuan-Ge Zhang,

Junjia Chen,

Zi-Yang Zhou

et al.

Chem Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 101295 - 101295

Published: March 1, 2025

Language: Английский

Citations

2
3-Oxabicyclo[3.1.1]heptanes as Isosteres of meta-Substituted Benzene Rings DOI
Jennifer Morvan, Evelien Renders, Peter Buijnsters

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Replacement of the aromatic rings in drug candidates with isosteric rigid sp3-rich scaffolds can improve physicochemical properties, increase chance progressing molecule development, and open new chemical space. Isosteres meta-substituted benzenes remain challenging due to difficulty mimicking exit vector angles bond distances. Herein, we report synthesis 1,5-disubstituted 3-oxabicyclo[3.1.1]heptanes (oxa-BCHeps), which serve as saturated isosteres phenyl a similar geometric arrangement. This structural motif be obtained under mild reaction conditions via acid-mediated isomerization (2-oxaspiro[3.3]heptan-6-yl)methanols using catalytic quantities pyridinium chloride (PyrHCl). We demonstrate utility this methodology by preparing various building blocks for use medicinal chemistry incorporating 3-oxa-BCHep into anticancer sonidegib, improving its such permeability, metabolic stability, solubility.

Language: Английский

Citations

2
Recent Progress in (3+3) Cycloadditions of Bicyclobutanes to Access Bicyclo[3.1.1]heptane Derivatives DOI
Jian‐Jun Feng

Synlett, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 28, 2024

Abstract The synthesis of bicyclo[3.1.1]heptane (BCHeps) derivatives, which serve as three-dimensional (3D) bioisosteres benzenes and are the core skeleton several terpene natural products, is garnering growing interest. (3+3) cycloadditions bicyclobutanes (BCBs) represent an attractive method for efficiently accessing (hetero)BCHep skeletons with 100% atom economy. Herein, we give a brief summary recent achievements in this approach diverse BCHep emphasizing our progress initial palladium-catalyzed vinyl oxiranes. 1 Introduction 2 Radical Cycloaddition Reaction 3 Polar 4 Palladium-Catalyzed Enantioselective 5 Conclusion

Language: Английский

Citations

8
Recent Progress in Accessing Multi-functionalized Caged Hydrocarbons: En Route to Highly Functionalized Saturated (Bio)isosteres of Benzene Rings DOI
Shota Nagasawa, Yoshiharu Iwabuchi

Synthesis, Journal Year: 2024, Volume and Issue: unknown

Published: July 4, 2024

Abstract Recently, many saturated bioisosteres of the benzene ring have been developed, and their applications in drug development evaluated. Most these are caged hydrocarbons, which rigid skeletons three-dimensional spaces. Recent efforts to synthesize hydrocarbons enabled access multi-functionalized congeners that expected be (bio)isosteres benzenes. This short review summarizes recently reported methods for obtaining (typically more than disubstituted) hydrocarbons. 1 Introduction 2 Proposed Structures Caged Hydrocarbons as Saturated (Bio)isosteres Benzene Ring: A Brief Summary 3 Access Multi-functionalized Hydrocarbons: De Novo Synthetic Approaches 3.1 Bicyclo[1.1.1]pentanes (BCPs) 3.2 Bicyclo[2.1.1]hexanes (BCHs) 3.3 Bicyclo[3.1.1]heptanes (BCHeps) 3.4 Others 4 C–H Functionalization 5 Conclusion

Language: Английский

Citations

7
Enantioselective dearomative formal (3+3) cycloadditions of bicyclobutanes with aromatic azomethine imines: access to fused 2,3-diazabicyclo[3.1.1]heptanes DOI Creative Commons
Xue-Chun Yang, Feng Wu, Wen‐Biao Wu

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(46), P. 19488 - 19495

Published: Jan. 1, 2024

We present the first enantioselective dearomative (3+3) cycloadditions of bicyclobutanes (BCBs) utilizing a chiral Lewis acid catalyst and bidentate chelating BCB substrates.

Language: Английский

Citations

7
Light-enabled scalable synthesis of bicyclo[1.1.1]pentane halides and their functionalizations DOI Creative Commons
Vasyl Ripenko, Vadym Sham, Vitalina Levchenko

et al.

Nature Synthesis, Journal Year: 2024, Volume and Issue: 3(12), P. 1538 - 1549

Published: Sept. 5, 2024

Language: Английский

Citations

5
Catalytic asymmetric synthesis of meta benzene isosteres DOI
Mingkai Zhang, Matthew Chapman, Bhagyesh R. Sarode

et al.

Nature, Journal Year: 2024, Volume and Issue: 633(8028), P. 90 - 95

Published: Aug. 21, 2024

Language: Английский

Citations

4
Palladium-Catalyzed Strain-Enabled [2π + 2σ] Cycloadditions of Vinyl Bicyclo[1.1.0]butanes with Methyleneindolinones DOI

Lan Zheng,

Yumin Yang, Zhiping Liu

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 26, 2024

A palladium-catalyzed [2π + 2σ] cycloaddition of vinyl bicyclo[1.1.0]butanes with methyleneindolinones has been developed. The reaction enables the construction spirobicyclo[2.1.1]hexanes bearing an all-carbon quaternary center in moderate to good yields excellent diastereoselectivities. This method features a broad substrate scope functional group compatibility. practical utility this protocol was further demonstrated by gram-scale synthesis and postsynthetic transformations desired product.

Language: Английский

Citations

3