Synthesis of Indoles and Pyrroles Utilizing Iridium Carbenes Generated from Sulfoxonium Ylides

Abstract

Sulfur (sulfonium and sulfoxonium) ylides are versatile synthetic precursors for a diverse range of chemical transformations [1] , e. g. they are widely used as methylene synthons in the formation of small rings such as epoxides, aziridines, and cyclopropanes from electrophilic substrates like aldehydes, imines, and enones. Recently, cycloadditions of sulfur ylides to a variety of electrophilic metal (Pd, Fe, Cu, Rh, or Au) associated intermediates have been explored for synthesis of heterocycles (Scheme 1; Type I). [2] Scheme 1. Sulfur ylide-based heterocycle synthesis via a metal-associated intermediate (Type I) or via a metal-carbene complex (Type II).

Cross‐Coupling of α‐Carbonyl Sulfoxonium Ylides with C−H Bonds

“…[2] This issue is particularly relevant in the context of relatively large-scale applications at alate stage of drug development, as illustrated in the multikilogram synthesis of MK-7246, adrug candidate with potential application against respiratory disease (Figure 1a). [3] In this case,the formation of ac arbon-carbon bond plausibly proceeds by electrophilic substitution by the reactive a,b-unsaturated b-amino-esters substrates. [3] In this case,the formation of ac arbon-carbon bond plausibly proceeds by electrophilic substitution by the reactive a,b-unsaturated b-amino-esters substrates.…”

“…[9] Herein, we show that a-carbonyl sulfoxonium ylides undergo efficient cross-coupling reactions with aC (sp 2 )ÀH bond of both arenes and heteroarenes in the presence of ar hodium catalyst, which does not require as acrificial oxidizing reagent. Data from control experiments support the sequence of steps depicted in Figure 1c.T hus,t he crosscoupling reaction described herein is strongly distinct from the single,p revious example of CÀHf unctionalization by a-carbonyl sulfoxonium ylides, [3] both in scope and in terms of mechanism.…”

Synthesis of Multi‐substituted Dihydropyrazoles by Copper‐Mediated [4+1] Cycloaddition Reaction of N‐Sulfonylhydrazones and Sulfoxonium Ylides

“…Melting points were measured with WRR digital point apparatus and not corrected. The sulfoxonium ylides were synthesized according to the previous literature …”

Ruthenium Catalyzed C−H Acylmethylation of N‐Arylphthalazine‐1,4‐diones with α‐Carbonyl Sulfoxonium Ylides: Highway to Diversely Functionalized Phthalazino‐fused Cinnolines

“…[10a-c] Our group has also recently reportedR h III -catalyzed additive-driven carbene insertion strategies fort he synthesis hydroxy-dihydroindazolo-fused phthalazine-diones andc innoline-fused phthalazine-dionesv ia annulation of a-diazo carbonyl compounds with 2-arylphthalazine-1,4-diones. [10d] In striking contrastt oa-diazo carbonyl compounds, sulfoxonium ylides are convenient and safer carbene precursors that have been utilized for o-acylmethylation, [11] and annulation [12] of different aromatic scaffolds, mainly through Rh/Ir catalysis (Scheme 1a).…”