Aryne 1,2,3-Trifunctionalization with Aryl Allyl Sulfoxides

Abstract

An aryne 1,2,3-trisubstitution with aryl allyl sulfoxides is accomplished, featuring an incorporation of C-S, C-O, and C-C bonds on the consecutive positions of a benzene ring. The reaction condition is mild with broad substrate scope. Preliminary mechanistic study suggests a cascade formal [2 + 2] reaction of aryne with S═O bond, an allyl S → O migration, and a Claisen rearrangement.

Discussion Addendum for: The Direct Acyl-Alkylation of Arynes. Preparation of Methyl 2-(2-acetylphenyl)acetate

“…29 A plausible mechanism for this process is shown below. They have also achieved similar relay chemistry with sulfoxides 56 and sulfonamides. 57,58,59 In 2016, Yoshida reported an advancement of this concept.…”

The Advances and Applications of Arynes and Their Precursors to Synthesize the Heterocyclic Compounds: A Review

“…Some symmetric and unsymmetric alkynes compounds were also synthesized with the help of aryne like benzyne catalytically under the microwave conditions where conventional heating takes long time for the reaction completion [19]. Along with the development of mild aryne generation conditions by Kobayashi and Hoye, aryne chemistry has commenced a renaissance in recent years [20,21]. Certain limitations, however, remain to be solved in aryne chemistry.…”

Tandem Aryne‐Capture/Sigmatropic Rearrangement as a Metal‐Free Entry to Functionalized N‐Aryl Pyrrolidines

“…Though tandema ryne capture/aza-Claisen rearrangements involving allyl amines are known [10] (Scheme 1b), when we commenced this study this proposal was conceptually unique.T hus, as showni nS cheme 1c,w ep ostulated that reaction of N-alkyl tetrahydropyridines 1 (readily available from the corresponding N-alkyl pyridinium salts [11] )w ith an aryne [12,13] 2,w ould be followedb yi somerization of the first-formed sp 2 -anion 3 to the more stable ylide 4,w hich would undergo sigmatropic rearrangementt og ive N-arylatedp yrrolidine 5;h owever, since rearrangements of analogous N-alkyl-tetrahydropyridinium ylides typicallyr equiree levated temperature, [14,15] (unlike acyclic ammonium ylides, whichrearrangerapidlyatambient or low temperatures [16] )i tw as envisaged that heatingm ight be required to execute the final step of the cascade. Though tandema ryne capture/aza-Claisen rearrangements involving allyl amines are known [10] (Scheme 1b), when we commenced this study this proposal was conceptually unique.T hus, as showni nS cheme 1c,w ep ostulated that reaction of N-alkyl tetrahydropyridines 1 (readily available from the corresponding N-alkyl pyridinium salts [11] )w ith an aryne [12,13] 2,w ould be followedb yi somerization of the first-formed sp 2 -anion 3 to the more stable ylide 4,w hich would undergo sigmatropic rearrangementt og ive N-arylatedp yrrolidine 5;h owever, since rearrangements of analogous N-alkyl-tetrahydropyridinium ylides typicallyr equiree levated temperature, [14,15] (unlike acyclic ammonium ylides, whichrearrangerapidlyatambient or low temperatures [16] )i tw as envisaged that heatingm ight be required to execute the final step of the cascade.…”

“…To circumvent these obstacles, we were attracted by the concept of am etal-free tandem aryne-capture/[2,3]-rearrangement,w hich would circumvent the need for salt formation, and would avoid issues with carbenoid capture. Though tandema ryne capture/aza-Claisen rearrangements involving allyl amines are known [10] (Scheme 1b), when we commenced this study this proposal was conceptually unique.T hus, as showni nS cheme 1c,w ep ostulated that reaction of N-alkyl tetrahydropyridines 1 (readily available from the corresponding N-alkyl pyridinium salts [11] )w ith an aryne [12,13] 2,w ould be followedb yi somerization of the first-formed sp 2 -anion 3 to the more stable ylide 4,w hich would undergo sigmatropic rearrangementt og ive N-arylatedp yrrolidine 5;h owever, since rearrangements of analogous N-alkyl-tetrahydropyridinium ylides typicallyr equiree levated temperature, [14,15] (unlike acyclic ammonium ylides, whichrearrangerapidlyatambient or low temperatures [16] )i tw as envisaged that heatingm ight be required to execute the final step of the cascade. As well as theoretically allowing metal-free access to N-aryl pyrrolidine analogues bearing dense contiguous substitution (including adjacent quaternary centres,ademanding structural motif difficult to access by other means [17] ), the method would also allow fur-ther synthetic modification and diversification by manipulation of the pendant 3-alkenyl substituent.…”