Stereocontrolled Radical Thiophosphorylation

Molhm Nassir; Michał Ociepa; Hai Jun Zhang; Lauren N. Grant; Bryan J. Simmons; Martins S. Oderinde; Yu Kawamata; Anthony N. Cauley; Michael A. Schmidt; Martin D. Eastgate; Phil S. Baran

doi:10.1021/jacs.3c05655

Stereocontrolled Radical Thiophosphorylation

Molhm Nassir, Michał Ociepa, Hai Jun Zhang, Lauren N. Grant, Bryan J. Simmons, Martins S. Oderinde, Yu Kawamata, Anthony N. Cauley, Michael A. Schmidt, Martin D. Eastgate, Phil S. Baran

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5 Scopus citations

Abstract

The first practical, fully stereoselective P(V)-radical hydrophosphorylation is presented herein by using simple, limonene-derived reagent systems. A set of reagents have been developed that upon radical initiation react smoothly with olefins and other radical acceptors to generate P-chiral products, which can be further diversified (with conventional 2e^- chemistry) to a range of underexplored bioisosteric building blocks. The reactions have a wide scope with excellent chemoselectivity, and the unexpected stereochemical outcome has been supported computationally and experimentally. Initial ADME studies are suggestive of the promising properties of this rarely explored chemical space.

Original language	English
Pages (from-to)	15088-15093
Number of pages	6
Journal	Journal of the American Chemical Society
Volume	145
Issue number	28
DOIs	https://doi.org/10.1021/jacs.3c05655
State	Published - 19 Jul 2023
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2023 American Chemical Society

Funding

Financial support for this work was provided by Bristol-Myers Squibb. M. N. thanks the Council for Higher Education and Fulbright Israel. M. O. was supported by the Polish National Agency for Academic Exchange (the Bekker programme no. PPN/BEK/2020/1/00111/U/00001). H.-J. Z. was supported by Shanghai Institute of Organic Chemistry. We are grateful to Dr. D.-H. Huang and Dr. L. Pasternack (Scripps Research) for NMR spectroscopic assistance; Dr. M. Gembicky for X-ray crystallographic analysis; Q. N. Wong, B. Sanchez and J. Chen for assistance with chiral SFC; Dr. A. F. Garrido Castro, Dr. G. Laudadio, Dr. N. Truax, Dr. M. Costantini for insightful discussions; T. E.-H. Ewing for analytical assistance; A. Rerick for proofreading the manuscript.

Funders	Funder number
Council for Higher Education and Fulbright Israel
Bristol-Myers Squibb
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
Narodowa Agencja Wymiany Akademickiej	PPN/BEK/2020/1/00111/U/00001

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abstract = "The first practical, fully stereoselective P(V)-radical hydrophosphorylation is presented herein by using simple, limonene-derived reagent systems. A set of reagents have been developed that upon radical initiation react smoothly with olefins and other radical acceptors to generate P-chiral products, which can be further diversified (with conventional 2e- chemistry) to a range of underexplored bioisosteric building blocks. The reactions have a wide scope with excellent chemoselectivity, and the unexpected stereochemical outcome has been supported computationally and experimentally. Initial ADME studies are suggestive of the promising properties of this rarely explored chemical space.",

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doi = "10.1021/jacs.3c05655",

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AU - Nassir, Molhm

AU - Ociepa, Michał

AU - Zhang, Hai Jun

AU - Grant, Lauren N.

AU - Simmons, Bryan J.

AU - Oderinde, Martins S.

AU - Kawamata, Yu

AU - Cauley, Anthony N.

AU - Schmidt, Michael A.

AU - Eastgate, Martin D.

AU - Baran, Phil S.

PY - 2023/7/19

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AB - The first practical, fully stereoselective P(V)-radical hydrophosphorylation is presented herein by using simple, limonene-derived reagent systems. A set of reagents have been developed that upon radical initiation react smoothly with olefins and other radical acceptors to generate P-chiral products, which can be further diversified (with conventional 2e- chemistry) to a range of underexplored bioisosteric building blocks. The reactions have a wide scope with excellent chemoselectivity, and the unexpected stereochemical outcome has been supported computationally and experimentally. Initial ADME studies are suggestive of the promising properties of this rarely explored chemical space.

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Stereocontrolled Radical Thiophosphorylation

Abstract

Bibliographical note

Funding

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