Thiol–Yne Coupling of Propargylamine under Solvent‐Free Conditions by Bond Anion Relay Chemistry: An Efficient Synthesis of Thiazolidin‐2‐ylideneamine

Abstract

Thiol–yne coupling of propargylamine with isothiocyanate has been developed under metal‐ and solvent‐free conditions. The addition of propargylamine to isothiocyanate gives propargylthiourea. This intermediate in situ undergoes intramolecular 5‐exo‐dig cyclization to give thiazolidin‐2‐ylideneamine. A through‐bond anion relay reaction occurs by attack of the sulfur (not the nitrogen) atom on the alkyne in a highly regioselective manner at ambient temperature. Wide varieties of thiazolidin‐2‐ylideneamine derivatives were formed in excellent yields.

Tandem Thioacylation‐Intramolecular Hydrosulfenylation of Propargyl Amines – Rapid Access to 2‐Aminothiazolidines

“…We found also that treatment of 19 with phenyl isothiocyanate in dichloromethane for 2 h at room temperature resulted in the formation of the thiazolidine 22a in good yield. This cyclization pathway appears to be general with amine 19 for the same types of isothiocyanates we have investigated previously delivering thiazolidines 22b–d (Table ) . While our own investigation was continuing, the Dethe lab reported that heating neat mixtures of propargylamines, including 19 , and an isothiocyanate does afford the corresponding thiazolidine, and we were able to reproduce this .…”

“…This cyclization pathway appears to be general with amine 19 for the same types of isothiocyanates we have investigated previously delivering thiazolidines 22b–d (Table ) . While our own investigation was continuing, the Dethe lab reported that heating neat mixtures of propargylamines, including 19 , and an isothiocyanate does afford the corresponding thiazolidine, and we were able to reproduce this . However, the divergence in product formation between the two labs on reaction of propargylamine 19 and phenylisothiocyanate when conducted in solution was troubling and we wished to elucidate the source of the discrepancy.…”

“…While these reactions are experimentally convenient, depending upon the structures of the precursors, there can be issues with aromatization and formation of other by‐products . Two recent reports from the Dethe group have shown that thiazolidines can be obtained in good yields via a three component coupling under copper(I) catalysis,, including asymmetric variants, and through heating (35–50 °C) neat mixtures of the amine and isothiocyanate . In these latter reports, no examples of either terminal alkynes, N‐unsubstituted propargylamines, or systems lacking substituents at the propargylic carbon were described.…”

Thiol–Yne Coupling of Propargylamine under Solvent‐Free Conditions by Bond Anion Relay Chemistry: An Efficient Synthesis of Thiazolidin‐2‐ylideneamine

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The editorial office of the European Journal of Organic Chemistry (EurJOC) was informed by a reader on August 8th, 2017, that in the original article [1] the explanation of the mechanism as anion relay chemistry (ARC) was erroneous and the melting points of some of the compounds were reported in too wide ranges.We apologize for the confusion. The corrected Scheme 1 is given below.

We have also measured the melting points of all these compounds again, and the correct values are given below:

(133-135°C), 4q (121-123°C), 4s (compound decomposed at higher temperature; no proper m.

7057

We are thankful to Professor Carl J. Lovely, The University of Texas at Arlington, for pointing out that we confused resonance structures with ARC and for bringing the wide ranges of the melting points to our attention.

The Authors

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“…The editorial office of the European Journal of Organic Chemistry (EurJOC) was informed by a reader on August 8th, 2017, that in the original article [1] the explanation of the mechanism as anion relay chemistry (ARC) was erroneous and the melting points of some of the compounds were reported in too wide ranges.…”