Stereocontrolled cyclization of inherently chiral medium-sized rings DOI Creative Commons
Nicolò Tampellini, Brandon Q. Mercado, Scott J. Miller

et al.

Published: Aug. 29, 2024

Asymmetric catalysis evolved as an elegant, efficient and sustainable approach for the synthesis of a multitude chiral molecules.1 However, imparting high levels stereocontrol in complex forms chirality remains significant challenge, particularly when known synthetic routes to target compounds are very few use harsh conditions. Medium-sized rings which display inherent often exhibit attractive properties drug development;2-5 yet, they suffer from limitations due challenging cyclization steps that form strained ring. In fact, no enantioselective method is inherently seven-membered lack local stereogenic elements. this work, we present organocatalytic strategy construct seven- eight-membered featuring under mild conditions with stereocontrol. Notably, same iminophosphorane catalyst orchestrates substrates two different ring sizes, mechanistic paradigms. Our results provide entry into enantioenriched, congested medium-sized feature configurational stability. We believe relying on control cyclization, could be adapted other ring-forming reactions presently or unattainable. The size versatility generality offer important precedent further study features may enable broad success these concepts broader platforms.

Language: Английский

Enantiocontrolled Cyclization to Form Chiral 7- and 8-Membered Rings Unified by the Same Catalyst Operating with Different Mechanisms DOI
Nicolò Tampellini, Brandon Q. Mercado, Scott J. Miller

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Chiral medium-sized rings, albeit displaying attractive properties for drug development, suffer from numerous synthetic challenges due to difficult cyclization steps that must take place form these unusually strained, atropisomeric rings sterically crowded precursors. In fact, catalytic enantioselective methods the formation of chiral seven-membered are unknown, and corresponding eight-membered variants also sparse. this work, we present a substrate preorganization-based, enantioselective, organocatalytic strategy construct seven- featuring chirality is intrinsic ring in absence singular stereogenic atoms or single bond axes chirality. The reactions proceed under mild conditions with high levels stereocontrol. Notably, same bifunctional iminophosphorane catalyst orchestrates substrates two different sizes, mechanistic paradigms. We envision size versatility method could guide further applications asymmetric catalysis other challenging reactions.

Language: Английский

Citations

1
Synthesis of Inherently Chiral Germepins via Rh-Catalyzed Enantioselective C–H Germylation DOI

Cheng-Gang Qian,

Yan Hong, Jingyu Li

et al.

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

Published: April 15, 2025

A rhodium-catalyzed enantioselective C-H germylation reaction was developed, enabling the synthesis of germepin derivatives with diverse substitutions. This study represents a rare application E-H/C-H (E = Si or Ge) dehydrogenation coupling reactions in synthesizing inherently chiral molecules, marking first successful seven-membered heterocycles containing group 14 elements. Compared to their structurally analogous tribenzosilepins, tribenzogermepins exhibit enhanced stereochemical stability under conditions. Furthermore, compatibility Si-H bond identical conditions highlights distinct reactivity and Ge-H bonds.

Language: Английский

Citations

0
Inherently Chiral Seven- and Eight-Membered Rings: Enantioselective Synthesis and Applications DOI
Yu Luo, Shuang Luo, Qiang Zhu

et al.

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Compared to smaller or larger rings, seven- and eight-membered carbo- heterocycles are typically nonplanar exhibit greater conformational rigidity. This property alone can impart chirality certain 7- 8-membered ring systems. Herein, we summarize recent achievements in the enantioselective synthesis of this class inherently chiral medium including both construction modification, as well applications ligands catalysts derived from these rigid cyclic scaffolds asymmetric catalysis.

Language: Английский

Citations

0
Stereocontrolled cyclization of inherently chiral medium-sized rings DOI Creative Commons
Nicolò Tampellini, Brandon Q. Mercado, Scott J. Miller

et al.

Published: Aug. 29, 2024

Asymmetric catalysis evolved as an elegant, efficient and sustainable approach for the synthesis of a multitude chiral molecules.1 However, imparting high levels stereocontrol in complex forms chirality remains significant challenge, particularly when known synthetic routes to target compounds are very few use harsh conditions. Medium-sized rings which display inherent often exhibit attractive properties drug development;2-5 yet, they suffer from limitations due challenging cyclization steps that form strained ring. In fact, no enantioselective method is inherently seven-membered lack local stereogenic elements. this work, we present organocatalytic strategy construct seven- eight-membered featuring under mild conditions with stereocontrol. Notably, same iminophosphorane catalyst orchestrates substrates two different ring sizes, mechanistic paradigms. Our results provide entry into enantioenriched, congested medium-sized feature configurational stability. We believe relying on control cyclization, could be adapted other ring-forming reactions presently or unattainable. The size versatility generality offer important precedent further study features may enable broad success these concepts broader platforms.

Language: Английский

Citations

0