Cycloaddition/Electrocyclic Ring Opening Sequence between Alkynyl Sulfides and Azodicarboxylates To Provide N,N-Dicarbamoyl 2-Iminothioimidates

Abstract

The α-oxidized thioimidates are useful bidentate ligands and are important motifs in pharmaceuticals, pesticides, and fungicides. Despite their broad utility, a direct route for their synthesis has been elusive. Herein, we describe a one-step synthesis of N,Ndicarbamoyl 2-iminothioimidates from easily accessible thioacetylenes and commercially available azodicarboxylates (20 examples, ≤99% yield). Additionally, the mechanism of the transformation was extensively explored by variable-temperature NMR, in situ IR, and quantum mechanical simulations. These experiments suggest that the reaction commences with a highly asynchronous [2 + 2] cycloaddition, which leads to a four-membered diazacyclobutene intermediate with a barrier consistent with the observed reaction rate. This intermediate was then isolated for subsequent kinetic measurements, which yielded an experimental barrier within 1 kcal/mol of the calculated barrier for a subsequent 4π electrocyclic ring opening leading to the observed iminothioimidate products. This method represents the first direct route to α-oxidized thioimidates from readily accessible starting materials.

Cycloaddition of Phenyltriazolinedione with Carbazole-Alkynes and Yne-Carbamates to Access Diazacyclobutenes

“…Recently, our group has been interested in the development of tactics to access the rare diazacyclobutene (DCB) motif for synthetic and biological applications. − Prior to our efforts in this area, the heterocycle had been studied primarily through computation − and prepared only infrequently. − Our initial efforts focused on the union of electron-rich thioalkyne nucleophiles 1 and nitrogenous electrophiles such as triazolinediones 2 (Scheme A,B) , and azodicarboxylates 6 (Scheme C) . We hypothesized that similar reactivity of nitrogen-containing alkyne nucleophiles (e.g., 9 and 10 ) might also react productively with triazolinediones to provide stable DCB products 11 (Scheme D).…”

“…11−14 Our initial efforts focused on the union of electron-rich thioalkyne nucleophiles 1 and nitrogenous electrophiles such as triazolinediones 2 (Scheme 1A,B) 1,2 and azodicarboxylates 6 (Scheme 1C). 3 We hypothesized that similar reactivity of nitrogen-containing alkyne nucleophiles (e.g., 9 and 10) might also react productively with triazolinediones to provide stable DCB products 11 (Scheme 1D). The results of these efforts are reported herein.…”

Synthesis of Aryl Thioalkynes Enabled by Electrophilic Sulfenylation of Alkynes and the Following Elimination

“…Aniline-derived aryl alkynes furnished the target products in good yields (2u and 2v), and no sulfenylation of the electron-rich arenes was detected. 88 Ferrocene-derived alkyne 1w was applicable, yielding the corresponding methylthioalkyne in excellent yield. An electron-rich hetero aromatic, thiophene-derived alkyne was also competent for this methylthioalkyne synthesis (2x).…”

“…Performing the model reaction in the standard conditions with 8 mmol of phenylacetylene ( 1a ), provided 2a in 75% yield. Treatment of 2a with azodicarboxylates furnished the diimino product 3 in 70% isolated yield . The [4 + 2] cycloaddition could be achieved with 2.0 equiv of copper chloride, delivering 1,2,3-trisubstituted naphthalene 4 in 60% yield .…”

Telescoped Oxidation and Cycloaddition of Urazoles to Access Diazacyclobutenes

“…Recently, our group was able to exploit the reactivity between 4-phenyl-1,2,4-triazoline-3,5-dione ( 1 , PTAD) and electron-rich thioalkynes 2 (X = S) to afford a group of stable diazacyclobutenes 3 , a hitherto rarely accessed scaffold (Scheme , eq 1) . Before our efforts in this area, there were only a few synthetic studies − and several computational studies ,,− on the scaffold. In our initial communication, we were able to substantially expand the scope of this scaffold by means of the ready access to a large variety of thio- and selenoalkynes 2 by simple operations, but the method lacked structural variety at the N 3 position of the triazolinedione (e.g., Ph in 1 ) component due to the lack of commercial triazolinediones except PTAD .…”