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Regiodivergent synthesis of sulfone-tethered lactam–lactones bearing four contiguous stereocenters

Sulfone-tethered lactones/amides/amines display a diverse spectrum of biological activities, including anti-psychotic and anti-hypertensive. Sulfones are also widely present in functional materials and fragrances. We therefore reasoned that a regiodivergent and stereocontrolled strategy that merges...

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Autores principales: Beng, Timothy K., Eichwald, Jane, Fessenden, Jolyn, Quigley, Kaiden, Sharaf, Sapna, Jeon, Nanju, Do, Minh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10340014/
https://www.ncbi.nlm.nih.gov/pubmed/37456540
http://dx.doi.org/10.1039/d3ra03800a
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author Beng, Timothy K.
Eichwald, Jane
Fessenden, Jolyn
Quigley, Kaiden
Sharaf, Sapna
Jeon, Nanju
Do, Minh
author_facet Beng, Timothy K.
Eichwald, Jane
Fessenden, Jolyn
Quigley, Kaiden
Sharaf, Sapna
Jeon, Nanju
Do, Minh
author_sort Beng, Timothy K.
collection PubMed
description Sulfone-tethered lactones/amides/amines display a diverse spectrum of biological activities, including anti-psychotic and anti-hypertensive. Sulfones are also widely present in functional materials and fragrances. We therefore reasoned that a regiodivergent and stereocontrolled strategy that merges the sulfone, lactone, and lactam motifs would likely lead to the discovery of new pharmacophores and functional materials. Here, we report mild conditions for the sulfonyllactonization of γ-lactam-tethered 5-aryl-4(E)-pentenoic acids. The annulation is highly modular, chemoselective, and diastereoselective. With respect to regioselectivity, trisubstituted alkenoic acids display a preference for 5-exo-trig cyclization whereas disubstituted alkenoic acids undergo exclusive 6-endo-trig cyclization. The lactam-fused sulfonyllactones bear angular quaternary as well as four contiguous stereocenters. The products are post-modifiable, especially through a newly developed Co-catalyzed reductive cross-coupling protocol.
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spelling pubmed-103400142023-07-14 Regiodivergent synthesis of sulfone-tethered lactam–lactones bearing four contiguous stereocenters Beng, Timothy K. Eichwald, Jane Fessenden, Jolyn Quigley, Kaiden Sharaf, Sapna Jeon, Nanju Do, Minh RSC Adv Chemistry Sulfone-tethered lactones/amides/amines display a diverse spectrum of biological activities, including anti-psychotic and anti-hypertensive. Sulfones are also widely present in functional materials and fragrances. We therefore reasoned that a regiodivergent and stereocontrolled strategy that merges the sulfone, lactone, and lactam motifs would likely lead to the discovery of new pharmacophores and functional materials. Here, we report mild conditions for the sulfonyllactonization of γ-lactam-tethered 5-aryl-4(E)-pentenoic acids. The annulation is highly modular, chemoselective, and diastereoselective. With respect to regioselectivity, trisubstituted alkenoic acids display a preference for 5-exo-trig cyclization whereas disubstituted alkenoic acids undergo exclusive 6-endo-trig cyclization. The lactam-fused sulfonyllactones bear angular quaternary as well as four contiguous stereocenters. The products are post-modifiable, especially through a newly developed Co-catalyzed reductive cross-coupling protocol. The Royal Society of Chemistry 2023-07-13 /pmc/articles/PMC10340014/ /pubmed/37456540 http://dx.doi.org/10.1039/d3ra03800a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Beng, Timothy K.
Eichwald, Jane
Fessenden, Jolyn
Quigley, Kaiden
Sharaf, Sapna
Jeon, Nanju
Do, Minh
Regiodivergent synthesis of sulfone-tethered lactam–lactones bearing four contiguous stereocenters
title Regiodivergent synthesis of sulfone-tethered lactam–lactones bearing four contiguous stereocenters
title_full Regiodivergent synthesis of sulfone-tethered lactam–lactones bearing four contiguous stereocenters
title_fullStr Regiodivergent synthesis of sulfone-tethered lactam–lactones bearing four contiguous stereocenters
title_full_unstemmed Regiodivergent synthesis of sulfone-tethered lactam–lactones bearing four contiguous stereocenters
title_short Regiodivergent synthesis of sulfone-tethered lactam–lactones bearing four contiguous stereocenters
title_sort regiodivergent synthesis of sulfone-tethered lactam–lactones bearing four contiguous stereocenters
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10340014/
https://www.ncbi.nlm.nih.gov/pubmed/37456540
http://dx.doi.org/10.1039/d3ra03800a
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