Iron-Catalyzed Prins–Peterson Reaction for the Direct Synthesis of Δ⁴-2,7-Disubstituted Oxepenes

Abstract

A direct iron­(III)-catalyzed Prins–Peterson reaction involving α-substituted γ-triphenylsilyl bis-homoallylic alcohols and aldehydes is described. Thus, cis-Δ4-2,7-disubstituted oxepenes were synthesized in a diastereoselective reaction using sustainable catalytic conditions (3–5 mol %). This highly productive process is the result of a cascade of three chemical events with the concomitant formation of a C–O bond, a C–C bond, and a Δ4 endocyclic double bond, through a Prins cyclization followed by a Peterson-type elimination. This tandem reaction is chemoselective vs the classical Prins cyclization.

Synthesis of Tetrahydroazepines through Silyl Aza-Prins Cyclization Mediated by Iron(III) Salts

“…Based on our previous work, which allowed the diastereoselective synthesis of oxepenes through the Prins-Peterson cyclization (PPC) strategy, 35 we decided to approach the nitrogen version and thus synthesize different tetrahydroazepines. If successful, it would constitute a direct and straightforward method that, using a sustainable iron(III) catalyst, builds a C–N, C–C bond and an endocyclic double bond in a single reaction step ( Scheme 1 ).…”

“…EtOH was purified by distillation and dried following the procedure in the literature. 35 Chemical reactions and the separation of the crudes were monitored by thin-layer chromatography (TLC). TLC was performed on aluminum foil sheets 60 F254 manufactured by MERCK.…”

Synthesis of Seven Membered Oxacycles: Recent Developments and New Approaches

“…In 2018, Padrón and co‐workers presented a study of the properties of iron‐based Lewis acids to catalyze the synthesis of Δ 4 ‐2,7‐disubstituted oxepenes (Scheme 4). [ 13 ]…”

Shortest Enantioselective Total Syntheses of (+)-Isolaurepinnacin and (+)-Neoisoprelaurefucin

“…The Prins–Peterson cyclization (PPC) is highly efficient and stereoselective and only requires a substoichiometric amount of FeBr 3 . 15 …”

“…It has the correct stereochemistry and would start from the unsaturated silyl alcohols 6 and ent - 6 . 15 …”