Enantioselective formal [4π+2σ] cycloaddition of bicyclobutanes with nitrones enabled by asymmetric Lewis acid catalysis DOI Creative Commons
Jian‐Jun Feng, Wen‐Biao Wu, Xue-Chun Yang

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Июнь 18, 2024

Abstract The absence of catalytic asymmetric methods for synthesizing chiral (hetero)bicyclo[n.1.1]alkanes has hindered their application in new drug discovery. Here we demonstrate the achievability an polar cycloaddition BCB using a Lewis acid catalyst and bidentate chelating substrate, as exemplified by current enantioselective formal [4π+2σ] BCBs with nitrones. In addition to diverse incorporating acyl imidazole group or pyrazole moiety, wide array nitrones are compatible this catalysis, successfully assembling two congested quaternary carbon centers aza-trisubstituted center pharmaceutically important hetero-bicyclo[3.1.1]heptane product up 99% yield >99% ee.

Язык: Английский

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

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Сен. 12, 2024

Язык: Английский

Процитировано

21
Pyridine-Boryl Radical-Catalyzed [3π + 2σ] Cycloaddition for the Synthesis of Pyridine Bioisosteres DOI Creative Commons
Honggen Wang, Yuan Liu,

Shuang Lin

и другие.

Опубликована: Апрель 1, 2024

The exploration of C(sp3)-rich three-dimensional (3D) scaffolds as bioisosteres for planar aromatics has garnered increasing attention. While the bioisosterism benzenes been extensively studied, pyridines, second most prevalent aromatic compounds in pharmaceuticals, faces additional challenges and encountered surprisingly limited success. In this study, we propose unprecedented 2-azabicyclo[3.1.1]heptenes effective 1,3,5-trisubstituted pyridines terms not only 3D conformation but also basicity. We develop a pyridine-boryl radical-catalyzed [3π + 2σ] cycloaddition reaction vinyl azides with bicyclo[1.1.0]butanes (BCBs) an efficient synthetic approach. Synthetic manipulation products reveals valuable handles, allowing modular synthesis various pyridine bioisosteres.

Язык: Английский

Процитировано

6
Recent Progress in (3+3) Cycloadditions of Bicyclobutanes to Access Bicyclo[3.1.1]heptane Derivatives DOI
Jian‐Jun Feng

Synlett, Год журнала: 2024, Номер unknown

Опубликована: Авг. 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

Язык: Английский

Процитировано

5
Enantioselective Dearomatizing 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

и другие.

Опубликована: Авг. 6, 2024

Although cycloadditions of bicyclobutanes (BCBs) have emerged as a reliable approach for producing bicyclo[n.1.1]alkanes such azabicyclo[3.1.1]heptanes (aza-BCHeps), serving saturated bioisosteres arenes, the catalytic asymmetric variant remains underdeveloped and presents challenges. Herein, we developed several Lewis acid-catalyzed systems challenging dearomatizing (3+3) cycloaddition BCBs aromatic azomethine imines. This resulted in fused 2,3-diazabicyclo[3.1.1]heptanes, introducing novel chemical space caged hydrocarbons. Moreover, an acid catalysis strategy was devised N-iminoisoquinolinium ylides, forming chiral diaza-BCHeps with up to 99% yield 97% ee. work represents first successful demonstration by environment through activation BCBs.

Язык: Английский

Процитировано

4
Diastereoselective Dearomative 1,3-Dipolar Cycloaddition of Bicyclobutanes with Pyridinium Ylides: A Modular Approach to Multisubstituted Azabicyclo[3.1.1]heptanes DOI Creative Commons

Kushal Dhake,

Kyla Woelk,

Liam D N Krueckl

и другие.

Опубликована: Авг. 1, 2024

We describe a formal 1,3-dipolar cycloaddition between bicyclobutanes and pyridinium ylides to form azabicycloheptanes via diastereoselective pyridine dearomatization. Microscale highthroughput experimentation led identification of conditions affording high yield stereoselectivity without the need for catalysis. These reactions proceed using as-received reagents solvents under ambient atmosphere. The resulting ring-fused azabicyclo[3.1.1]heptanes have diverse synthetic handles further transformations, making them potentially valuable scaffolds design Csp3-rich drug candidates. also demonstrate photochemical skeletal rearrangement give 1,1,3,3-tetrasubstitued cyclobutane.

Язык: Английский

Процитировано

2
Enantioselective formal [4π+2σ] cycloaddition of bicyclobutanes with nitrones enabled by asymmetric Lewis acid catalysis DOI Creative Commons
Jian‐Jun Feng, Wen‐Biao Wu, Xue-Chun Yang

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Июнь 18, 2024

Abstract The absence of catalytic asymmetric methods for synthesizing chiral (hetero)bicyclo[n.1.1]alkanes has hindered their application in new drug discovery. Here we demonstrate the achievability an polar cycloaddition BCB using a Lewis acid catalyst and bidentate chelating substrate, as exemplified by current enantioselective formal [4π+2σ] BCBs with nitrones. In addition to diverse incorporating acyl imidazole group or pyrazole moiety, wide array nitrones are compatible this catalysis, successfully assembling two congested quaternary carbon centers aza-trisubstituted center pharmaceutically important hetero-bicyclo[3.1.1]heptane product up 99% yield >99% ee.

Язык: Английский

Процитировано

0