A Short Synthesis of the 8-Azaergoline Ring System by Intramolecular Tandem Decarboxylation−Cyclization of the Minisci-Type Reaction

Minisci reactions: Versatile CH-functionalizations for medicinal chemists

“…One of the earlier examples of an intramolecular Minisci reaction, in the synthesis of a biologically-important scaffold, was provided by the synthesis of an aza-ergoline ring structure 70, available in three-steps from commercially-available indole-4-boronic acid 68; the key cyclization step used a Minisci reaction of an acyl radical (Scheme 43). 128 Of note, was the absence of an indole protecting group in this short reaction sequence, clearly supporting the idea that Minisci chemistry does not necessarily benefit from a protecting group. Similar intramolecular radical reactions have very recently been described by Bennasar and Roca to obtain ergoline-related indole-fused isoquinolines (Scheme 43).…”

“…143 However, a few selective examples are shared here for illustrative purposes.Scheme 44 A cascade approach to a relative of the anti-inflammatory alkaloid, Spongidine A 130. Scheme 43 Intramolecular Minisci reactions to provide ''aza-ergoline'' ring structures 128,129.…”

Study of Radical Decarboxylation Toward Functionalization of Naphthoquinones

“…The experimental procedure was realized in a homogeneous solvent mixture, which insured solubility of all reaction components (see Experimental Section). In the case of the Minisci reaction, either a two‐phase mixture12,17 or a strong acidic medium has been used 15. While the latter conditions were unsuitable with a tert ‐butyl carbamate protecting group and led to unpredictable results in the case of α‐amino acids, they also gave an unexpected (and in our case undesired) regioselectivity when M was used 12.…”

Synthesis of a cytisine/epibatidine hybrid: a radical approach

“…36 Whereas the intramolecular reaction of pyridyl radicals 37e39 with alkenes (or alkynes or arenes), or that of alkenyl or aryl radicals with pyridines (or related heterocycles) 40,41 have been widely studied, the radical cyclization of a primary radical on a pyridine nucleus has received less attention. 42 Fused heteroaromatic ring systems were successfully prepared by intramolecular reaction of primary alkyl radicals generated from 1-(iodoalkyl)pyridinium iodides, 43 or from 2-aminopyridinyl alkyl xanthates. 44 A selective reaction of tertiary alkyl radicals at the 2-position of a 3-substituted pyridine ring was observed in an approach to the synthesis of spongidines.…”