Access to Broad Organosulfur Chemical Space by Iron MHAT Sulfinamidation of Olefins
- 1Small Molecule Drug Discovery, Bristol Myers Squibb, 250 Water St, Cambridge, MA, USA, 02143
Abstract
Organosulfur groups, particularly in the S(VI) oxidation state, have seen increased adoption within the medicinal chemistry community in recent years. Although certain groups such as sulfones and sulfonamides have been utilized since the advent of modern drug development, others like sulfonimidamides or sulfoximines have only recently seen utilization. These desirable functionalities provide access to new chemical space and intellectual property while enabling the optimization of key ADME properties. Herein, we disclose a new method for the construction of these key organosulfur motifs via the hydrosulfinamidation of olefins. This transformation relies upon stoichiometric, low-cost Fe(acac)3 to interconvert an olefin into an alkyl radical via MHAT, which is then trapped by a sulfinylamine (e.g. TrNSO) to deliver S(IV) species, with exclusive Markovnikov selectivity. These sulfinamides serve as diversifiable lynchpins for readily accessing their aza-S(VI) congeners. Furthermore, we demonstrate this transformation’s practicality at preparative scale (>20-grams of product), enabling access to complex organosulfur modalities using inexpensive reagents and simple conditions.
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BibTeX
@misc{kaydosdaniels2026access,
title = {{Access to Broad Organosulfur Chemical Space by Iron MHAT Sulfinamidation of Olefins}},
author = {Sylvia Kaydos-Daniels and Zachary F. Murphy and Erik C. Vik and Noah B. Bissonnette},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15009611/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009611/v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Access to Broad Organosulfur Chemical Space by Iron MHAT Sulfinamidation of Olefins
AU - Sylvia Kaydos-Daniels
AU - Zachary F. Murphy
AU - Erik C. Vik
AU - Noah B. Bissonnette
PY - 2026
DA - 2026/09/29
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009611/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009611/v1
AB - Organosulfur groups, particularly in the S(VI) oxidation state, have seen increased adoption within the medicinal chemistry community in recent years. Although certain groups such as sulfones and sulfonamides have been utilized since the advent of modern drug development, others like sulfonimidamides or sulfoximines have only recently seen utilization. These desirable functionalities provide access to new chemical space and intellectual property while enabling the optimization of key ADME properties. Herein, we disclose a new method for the construction of these key organosulfur motifs via the hydrosulfinamidation of olefins. This transformation relies upon stoichiometric, low-cost Fe(acac)3 to interconvert an olefin into an alkyl radical via MHAT, which is then trapped by a sulfinylamine (e.g. TrNSO) to deliver S(IV) species, with exclusive Markovnikov selectivity. These sulfinamides serve as diversifiable lynchpins for readily accessing their aza-S(VI) congeners. Furthermore, we demonstrate this transformation’s practicality at preparative scale (>20-grams of product), enabling access to complex organosulfur modalities using inexpensive reagents and simple conditions.
ER -