Facile Synthesis of Sulfonyl Chlorides/Bromides from Sulfonyl Hydrazides

A simple and rapid method for efficient synthesis of sulfonyl chlorides/bromides from sulfonyl hydrazide with NXS (X = Cl or Br) and late-stage conversion to several other functional groups was described. A variety of nucleophiles could be engaged in this transformation, thus permitting the synthesis of complex sulfonamides and sulfonates. In most cases, these reactions are highly selective, simple, and clean, affording products at excellent yields.

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A Practical and General Approach to the Late-Stage Functionalization of Complex Sulfonamides

10.26434/chemrxiv.7550117.v1 ◽

2019 ◽

Author(s):

Patrick Fier ◽

Kevin M. Maloney

Keyword(s):

Functional Groups ◽

Late Stage ◽

Building Blocks ◽

Pharmaceutical Compounds ◽

Stage Conversion

Herein we describe the development and application of a method for the mild, late-stage conversion of primary sulfonamides to several other other functional groups. These reactions occur via initial reductive deamination of sulfonamides to sulfinates via an NHC-catalyzed reaction of transiently formed <i>N</i>-sulfonylimines. The method described here is tolerant of nearly all common functional groups, as exemplified by the late-stage derivatization of several complex pharmaceutical compounds. Based on the prevalence of sulfonamide-containing drugs and building blocks, we have developed a method to enable sulfonamides to be applied as versatile synthetic handles for synthetic chemsitry.

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A Practical and General Approach to the Late-Stage Functionalization of Complex Sulfonamides

10.26434/chemrxiv.7550117 ◽

2019 ◽

Author(s):

Patrick Fier ◽

Kevin M. Maloney

Keyword(s):

Functional Groups ◽

Late Stage ◽

Building Blocks ◽

Pharmaceutical Compounds ◽

Stage Conversion

Herein we describe the development and application of a method for the mild, late-stage conversion of primary sulfonamides to several other other functional groups. These reactions occur via initial reductive deamination of sulfonamides to sulfinates via an NHC-catalyzed reaction of transiently formed <i>N</i>-sulfonylimines. The method described here is tolerant of nearly all common functional groups, as exemplified by the late-stage derivatization of several complex pharmaceutical compounds. Based on the prevalence of sulfonamide-containing drugs and building blocks, we have developed a method to enable sulfonamides to be applied as versatile synthetic handles for synthetic chemsitry.

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Efficient synthesis of 1,2-benzisothiazoles from o-haloarylamidines and elemental sulfur via N–S/C–S bond formation under transition-metal-free conditions

Green Chemistry ◽

10.1039/c7gc03599c ◽

2018 ◽

Vol 20 (4) ◽

pp. 827-831 ◽

Cited By ~ 14

Author(s):

Hao Xie ◽

Guozheng Li ◽

Feng Zhang ◽

Fuhong Xiao ◽

Guo-Jun Deng

Keyword(s):

Transition Metal ◽

Functional Groups ◽

Elemental Sulfur ◽

Bond Formation ◽

Efficient Synthesis ◽

Facile Synthesis ◽

Good Tolerance ◽

Metal Free

Facile synthesis of 1,2-benzisothiazoles from amidines and elemental sulfur via N–S/C–S bond formation under transition-metal-free conditions has been developed with good tolerance of a broad range of functional groups.

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Reductive Cleavage of Secondary Sulfonamides: Converting Terminal Functional Groups into Versatile Synthetic Handles

10.26434/chemrxiv.9925145 ◽

2019 ◽

Author(s):

Patrick Fier ◽

Suhong Kim ◽

Kevin M. Maloney

Keyword(s):

Functional Groups ◽

Late Stage ◽

Reductive Cleavage ◽

Bioactive Molecules ◽

General Method

Sulfonamides are pervasive in drugs and agrochemicals, yet are typically considered as terminal functional groups rather than synthetic handles. To enable the general late-stage functionalization of secondary sulfonamides, we have developed a mild and general method to reductively cleave the N-S bonds of sulfonamides to generate sulfinates and amines, components which can further react <i>in-situ</i> to access a variety of other medicinally relevant functional groups. The utility of this platform is highlighted by the selective manipulation of several complex bioactive molecules.

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Late-Stage Sulfoximination: Improved Synthesis of the Anticancer Drug Candidate Atuveciclib

Synthesis ◽

10.1055/s-0037-1610316 ◽

2018 ◽

Vol 51 (04) ◽

pp. 971-975 ◽

Cited By ~ 7

Author(s):

Vincent Reboul ◽

Thomas Glachet ◽

Xavier Franck

Keyword(s):

Anticancer Drug ◽

Late Stage ◽

Drug Candidate ◽

Efficient Synthesis ◽

Reaction Conditions

An efficient synthesis of racemic atuveciclib was accomplished in five steps with an excellent 51% overall yield, using cheap reagents and mild reaction conditions. The key sulfoximination reaction was realized during the last step of the synthesis from the corresponding sulfide.

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A facile synthesis of sulfonyl chlorides

Canadian Journal of Chemistry ◽

10.1139/v76-067 ◽

1976 ◽

Vol 54 (3) ◽

pp. 498-499 ◽

Cited By ~ 18

Author(s):

Richard F. Langler

Keyword(s):

Acetic Acid ◽

Aqueous Acetic Acid ◽

Sulfenyl Chloride ◽

Molecular Chlorine ◽

Facile Synthesis ◽

Sulfonyl Chlorides

Benzylic sulfides have been shown to furnish sulfonyl chlorides in excellent yields, upon reaction with molecular chlorine in aqueous acetic acid. The reaction most likely proceeds through the intermediacy of the corresponding sulfenyl chloride.

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Carbon dioxide-based facile synthesis of cyclic carbamates from amino alcohols

Chemical Communications ◽

10.1039/c8cc00636a ◽

2018 ◽

Vol 54 (25) ◽

pp. 3166-3169 ◽

Cited By ~ 27

Author(s):

Teemu Niemi ◽

Israel Fernández ◽

Bethany Steadman ◽

Jere K. Mannisto ◽

Timo Repo

Keyword(s):

Carbon Dioxide ◽

Amino Alcohols ◽

Efficient Synthesis ◽

Facile Synthesis

Selective, straightforward, and efficient synthesis of cyclic carbamates from CO2 and amino alcohols.

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Calcium mediated efficient synthesis of N-arylamidines from organic nitriles and amines

Organic & Biomolecular Chemistry ◽

10.1039/d0ob00805b ◽

2020 ◽

Vol 18 (22) ◽

pp. 4231-4237

Author(s):

Indrani Banerjee ◽

Shweta Sagar ◽

Tarun K. Panda

Keyword(s):

Solvent Free ◽

Efficient Synthesis ◽

Facile Synthesis ◽

Solvent Free Conditions ◽

One Step

An efficient one-step methodology for the facile synthesis of N-arylamidines from organic nitriles and amines by using calcium bis(hexamethyldisilazide) as a competent catalyst under solvent-free conditions is reported.

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A Single-Step Synthesis of Azetidine-3-Amines

10.26434/chemrxiv.12846629.v1 ◽

2020 ◽

Author(s):

Brian J Wang ◽

Matthew Duncton

Keyword(s):

Functional Groups ◽

Late Stage ◽

Single Step ◽

Secondary Amines ◽

High Yield ◽

Primary Amines ◽

Privileged Structure ◽

One Step ◽

Alternative Procedures ◽

Approved Drugs

<div> <p>The azetidine group is frequently encountered within contemporary medicinal chemistry where it is viewed as a privileged structure. However, the introduction of an azetidine can be synthetically challenging. Herein, a straight-forward one step synthesis of azetidine-3-amines, starting from a bench stable, commercial material is presented. The reaction tolerates functional groups commonly encountered in biological-, medicinal- and agro-chemistry, and proceeds in moderate-to-high yield with secondary amines, and moderate-to-low yield with primary amines. The methodology compares favorably to recent alternative procedures and can be utilized in “any-stage” functionalization, including late-stage azetidinylation of approved drugs and other compounds with pharmacological activity.</p> </div>

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