Silver Trifluoromethanesulfonate-Catalyzed Annulation of Propargylic Alcohols with 3-Methyleneisoindolin-1-one

Abstract

A silver-catalyzed formal [3 + 3] annulation of 3-methyleneisoindolin-1-one with alkynol for the synthesis of 1,5-dihydroindolizin-3­(2H)-one derivatives is disclosed. The protocol allows practical synthesis of N-heterocyclic scaffolds with a broad scope of functional groups and could be efficiently scaled up to gram scale, which incarnates a potential application of this methodology. In addition, a range of chlorine anion substitution of alkenes can be constructed by adjusting the structure of the alkynol substrates with the use of TMSCl.

Recent Advances in the Synthesis of Heterocyclics via Cascade Cyclization of Propargylic Alcohols

“…More recently, an efficient AgOTf‐catalyzed [3+3]‐annulation of propargylic alcohols 1 and 3‐methyleneisoindolin‐1‐ones 41 has been accomplished by Liang's group (Scheme 14). [24] Various aromatic and aliphatic propargylic alcohols were well tolerated in this transformation, leading to the 1,5‐dihydroindolizing‐3(2 H )‐one derivatives 42 , which are prevalent in a variety of natural products and biologically active molecules. Moreover, such skeletons were also widely used as synthetic intermediates in organic synthesis.…”

Recent approaches for the synthesis of pyridines and (iso)quinolines using propargylic Alcohols

“…Liang and co-workers, in the year 2020, demonstrated a AgOTf-catalyzed synthesis of 1,5-dihydroindolizin-3(2 H )-one derivatives 71 through a [3 + 3] annulation between 3-methyleneisoindolin-1-ones 72 and tertiary -propargylic alcohols 73 . 33 They explored a wide range of substituted propargylic alcohols and 3-methyleneisoindolin-1-ones for the generation of novel 1,5-dihydroindolizin-3(2 H )-ones in moderate to good yields (Scheme 14A). Unfortunately, no annulation product was observed with the secondary-propargylic alcohols.…”

Influence of N‐Substitution in 3‐Alkyl‐3‐hydroxyisoindolin‐1‐ones on the Stereoselectivity of Brønsted Acid‐Catalyzed Synthesis of 3‐Methyleneisoindolin‐1‐ones

“…The presence of an exocyclic double bond renders 3‐methyleneisoindolin‐1‐ones useful substrates in further functionalization, such as annulation with propargylic alcohols, [12] intramolecular arylation, [13] and oxidative C−H amination [14] . Moreover, several isoindolin‐1‐one alkaloids exhibiting pain‐alleviating properties contain either Z ‐ or E ‐configured stilbenoid unit.…”