Sulfonyl Azoles in the Synthesis of 3-Functionalized Azole Derivatives

Abstract

Sulfonyl indoles, as well as related azolyl derivatives, have been recently introduced in synthesis as stable precursors of reactive indolenine intermediates. This personal account reports on the discovery of sulfonyl azoles and their practical utilization in many synthetic processes for the preparation of functionalized 3-substituted indoles, indazoles, and pyrroles. The indolenine intermediates obtained by treatment of sulfonyl azoles with Brønsted bases or Lewis acids can be considered as vinylogous imino derivatives that can be made to react with different nucleophilic reagents. These include organometallic reagents, reducing agents, stabilized carbanions, and heteronucleophiles. The controlled and mild conditions for the generation of indolenines from sulfonyl azoles make these substrates particularly useful in asymmetric synthesis, exploiting organo- or metal-catalyzed processes. Although less exploited, sulfonyl indoles can also be involved in photochemical processes for the preparation of polycyclic derivatives.

Regioselective Direct C‐Alkenylation of Indoles

“…The whole procedure is based on the well-known chemistry of sulfonylindoles 113 which are formed by exchange of the hydroxy group in the initially formed alco-hol 112 by phenylsulfinica cid. [177] Under basic conditions the phenylsulfonyl group is removed giving ar eactive alkylideneindolenine 114 whichi nt he presence of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) is deprotonated to afford the final product. Interestingly,NaH alone is unable to furnisht he wanted alkenyl derivative and therefore DBU is mandatory for an efficient process.…”

Organocatalytic Enantioselective Synthesis of Chiral Allenes: Remote Asymmetric 1,8‐Addition of Indole Imine Methides

“…[7] Recently, indole-based imine methides, typically generated from indolylmethanols, have proven to be versatile in providing direct access to enantioenriched indole derivatives by organocatalysis, particularly with nucleophiles because of their intrinsic electrophilic nature. [8] Various asymmetric reaction modes of indole-based imine methides have been documented, [8] especially on cycloaddition [9] and either 1,4-or 1,6-conjugate addition. [10] However, among these examples, limited success was achieved for remote asymmetric addition (e.g., 1,8-addition), which is undoubtedly an inherent challenge because of issues like regioselectivity and stereocontrol.…”

Synthesis of Unsymmetrical Bisindolylmethanes by Reaction of Indolylmagnesium Bromides with Sulfonyl Indoles

“…Conversion of gramines into the corresponding ammonium salts ( I , Lg=NR 3 I) allows a ready elimination of a tertiary amine resulting in an efficient addition of several azole derivatives . 3‐(1‐Arylsulfonylalkyl) indoles (sulfonyl indoles I , Lg=SO 2 Ar) have been discovered by us more than a decade ago and since then have emerged as reliable precursors of both cationic intermediates III and alkylideneindolenines V . Sulfonyl indoles can be readily prepared by an acid catalyzed three component coupling of aldehydes, indoles and arylsulfinic acids and this reaction has been previously used for the synthesis of unsymmetrical arylsulfonyl bisindolylmethanes starting from indole‐3‐carboxaldehydes .…”