Transition-Metal-Free Thioamination of Arynes Using Sulfenamides

Abstract

The insertion of arynes into the S–N σ-bond of sulfenamides allowing the synthesis of o-sulfanylaniline derivatives with reasonable functional group compatibility is presented. The aryne generated from 2-(trimethylsilyl)­aryl triflates using CsF in DME was the key for the success of this transition-metal-free thioamination reaction, which involves new C–N and C–S bond formations in a single step under mild conditions. Moreover, the synthetic potential of this method was demonstrated by the synthesis of the antidepressant drug vortioxetine.

Leaving Groups in Metal‐Free Arylations: Make Your Choice!

“…The approach, that involved the insertion of a generated aryne into the S-N σ-bond of a sulfonamide moiety, was also applied to the multistep preparation in good yields of antidepressant drug vortioxetine 16 (Scheme 14) via -sulfanylaniline 15 intermediate. [74] Scheme 14. Two-step synthesis of vortioxetine 16.…”

“…Two-step synthesis of vortioxetine 16. [74] On the other hand, since the early pioneering works of Havinga [75] great attention has been given to the photochemical activation of aryl phosphates and solfonates. A decade ago, looking for new classes of photoactivatable aromatic substrates, our group discovered that electron rich aryl solfonates (triflates and mesylates) and diethylphosphates undergo photoinduced Ar-O bond heterolytic cleavage, and the resulting triplet aryl cation was exploited in metal-free arylation via triplet aryl cations, such as phenylation [76] and alkynation [34] of arenes (Scheme 15) A similar reactivity was found in the case of aryl nonaflates (Ar-OSO 2 C 4 F 9 ) [77] and trifluoroethoxy aryl sulfates.…”

Über bislang nicht beachtete Parallelen in der Reaktivität von Arinen und Donor‐Akzeptor‐Cyclopropanen

“…Mit Sulfonamiden wurde das entsprechende Ringöffnungsprodukt ebenfalls nachgewiesen, jedoch nur in sehr geringen Ausbeuten. Im Bereich der Arinchemie wurde die S‐N‐Insertion von Biju und Mitarbeitern mit Sulfenamiden entwickelt . Die schwache N‐S‐σ‐Bindung ist leicht zu brechen, und es wurden 1,2‐Sulfanylaniline gewonnen.…”

Synthesis of Stannylated Aryl Imines and Amines via Aryne Insertion Reactions into Sn−N Bonds

“…Moreover, various methods for the construction of CÀ N and CÀ Sn bonds involving aryne intermediates are known. [31][32][33][34][35][36][37][38][39] Inspired by our previously reported stannylphosphanylation of aryne intermediates that uses stannylated phosphanes as reagents, [31] we herein report a practical method to implement an N-substituent to an aryl compound along with a stannyl moiety in ortho position via aryne insertion into the NÀ Sn bond of a stannylated imine (Scheme 1C). Notable features of the novel method are: a) the imine functionality installed serves as a protecting group and the free anilines are readily obtained upon simple hydrolysis; b) the simultaneously formed ortho-Snaryl bond has a large synthetic value which is documented by several follow-up reactions showing the diversity that can be achieved by using this approach.…”