Iodide-Catalyzed Synthesis of Secondary Thiocarbamates from Isocyanides and Thiosulfonates

Abstract

A new method for the synthesis of secondary thiocarbamates from readily available isocyanides and thiosulfonates with broad functional group tolerance is reported. The reaction proceeds under mild reaction conditions in isopropanol and is catalyzed by inexpensive sodium iodide.

One‐Pot Synthesis of Thiocarbamates

“…Thiocarbamates are a well-established substance class within organic chemistry. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Their versatility is partially derived from their isomeric character: O-organyl and S-organyl thiocarbamates as well as dithiocarbamates are well known. Some are biologically active and hence they have found applications as antifertility agents, antivirals, pesticides and herbicides (e. g. the S-organyl thiocarbamates Thiobencarb, Orbencarb, and Molinate).…”

“…Some are biologically active and hence they have found applications as antifertility agents, antivirals, pesticides and herbicides (e. g. the S-organyl thiocarbamates Thiobencarb, Orbencarb, and Molinate). [4,[17][18][19] However, preparation of S-organyl thiocarbamates involves toxic starting materials or intermediates. [10,20,21] Their synthesis often relies on the conversion of phosgene or its derivatives by subsequent addition of an amine and a thiol or vice versa or, alternatively, the conversion of organic isocyanates utilizing thiols.…”

“…[32] In the last decade, several new routes toward S-thiocarbamates have been published starting with the work of Maes et al in 2016, who employed isocyanides for their synthesis. [4] These were converted by thiosulfonates and iodine as catalyst that are, like isocyanides, far easier to handle than either phosgene or isocyanates, especially on laboratory scale (Scheme 1). In the following years, the working groups of Sun, Yang, Wei Wei and Khalaj also exploited this newfound reactivity of isocyanides to access a wide variety of Sthiocarbamates in good yields, by utilizing the thermolysis of sulfoxides, a photochemical reaction of thiols, an iodinecatalyzed conversion of sulfinates or in a three-component reaction with elemental sulfur and an aryl iodide.…”

Efficient Synthesis of Sulfenamides through Mitsunobu‐type Coupling Reaction of Thiols with Amines using Dibenzyl Azodicarboxylate

“…The reactions with thiophenol and selenophenol proceeded with excellent yields of 99% and 97%, respectively. Thiophenols with methyl, methoxy or trifluoromethyl groups at the para ‐position were tolerated well, and generated the desired products 4 c, 4 e , and 4 f in yields of 99%, 99% and 94%, respectively. The reaction with 2,6‐dimethylthiophenol led to the formation of the corresponding product 4 d in 97% yield.…”

KI-catalyzed synthesis of S-Thiocarbamates by cross-coupling of cyclohexyl isocyanide with sulfonyl chlorides

“…Classic methods for the synthesis of S-Thiocarbamates include (1) reacting toxic phosgene/triphosgene or carbonyldiimidazole with an amine and thiophenol (Scheme 1(a)), 14,15 (2) visible-light/ rose bengal reactions (Scheme 1(b)), 7,16 and (3) molecular iodine-catalyzed reactions of thiosulfonates (prepared from thiols or sulfonyl chlorides) with isocyanides (Scheme 1(c)). 17 However, these methods have shortcomings such as poor atom economy, harsh reaction conditions, and the use of difficult-to-obtain precursors as well as unstable, toxic, and/or hazardous chemical reagents. 7 Thus, it is necessary to develop an efficient and general route for the construction and enrichment of S-Thiocarbamate compounds.…”