Minisci reactions: Versatile CH-functionalizations for medicinal chemists

A new era for homolytic aromatic substitution: replacing Bu3SnH with efficient light-induced chain reactions

“…63 The intermediate Ir(IV) is proposed to facilitate the substitution by performing a SET oxidation of the -cyclohexadienyl radical, which deprotonates to give the aromatic product to regenerate the catalyst. As part of a late stage functionalization of bioactive heterocycles, Minisci-style substitutions 8,38 were demonstrated by methylation of quinoline under acidic conditions using acyl peroxide (Scheme 21).…”

Hypervalent Iodine(III) in Direct Carbon–Hydrogen Bond Functionalization

“…Additional shortcomings include low site selectivity, incomplete conversion, limited substrate scope, and the usage of metals in up to stoichiometric amounts. 24 Direct acylation of heterocycles with aldehydes is particularly challenging owing to the electron-deficient nature of both partners.…”

Synthesis and Utility of Dihydropyridine Boronic Esters

“…Thus,addition to benzaldehyde afforded the desired homoallylic alcohols (AE)-74-78 stereoselectively.A lternatively,o xidation of the boronic esters with sodium perborate gave the corresponding 6 ]/ NaBH 4 generated the enamide (AE)-85 with very high diastereoselectivity. [21] X-ray crystallography confirmed the surprising observation that [Mo(CO) 6 ]/NaBH 4 isomerized the olefin to form the conjugated (AE)-85. [22] Alternatively,hydrogenation with Pd/C gave the tetrasubstituted piperidine (AE)-86 with ad .r.…”

“…[5] Alternatively,M inisci reactions feature addition of alkyl or aryl radicals to aheteroarene.P oor regioselectivity is usually observed, and the 2-substituted products generally predominate (Scheme 1b). [6] Tr ansition metal catalyzed coupling reactions can also generate substituted pyridines,but they do not provide dearomatized products. [7] Recently,C ÀHf unctionalization strategies have emerged as attractive routes to the pyridine scaffold.…”