Prins Spirocyclization for the Synthesis of Spiro[isobenzofuran‐pyran] Derivatives

Abstract

A Prins cascade process was developed for the synthesis of tetrahydro‐3H‐spiro[isobenzofuran‐pyran] derivatives in good yields and selectivity by the condensation of 3‐[2‐(hydroxymethyl)phenyl]but‐3‐en‐1‐ols with aldehydes or ketones. The reaction proceeds smoothly in the presence of indium(III) trifluoromethanesulfonate (30 mol‐%) in dichloroethane at 80 °C. This is the first report on the synthesis of tetrahydro‐3H‐spiro[isobenzofuran‐pyran] scaffolds through a Prins cascade reaction.

Total Syntheses and Biological Activities of Vinylamycin Analogues

“…After exchanging the PMB protecting group with TBDPS to obtain compounds 15a – e , an additional two steps of deprotection were performed, and the intermediates were cyclized using HATU and DIPEA to provide compounds 2a – e . The TBS protection group in 2a – e was selectively deprotected under acidic conditions. , Mesylation of the resulting alcohol, followed by elimination with DBU, led to the production of O-TBDPS- ent -vinylamycin 1a, (14 S ,15 S ,16 R )-O-TBDPS-vinylamycin 1b , O-TBDPS-vinylamycin 1c , O-TBDPS- ent -5-demethylvinylamycin 1d , and O-TBDPS ent -5-demethyl-6-methylvinylamycin 1e .…”

Recent Advances in Prins Spirocyclization

“…After the use of phenolic oxygen as a nucleophile, a benzyl hydroxy group was also successfully deployed in a cascade Prins reaction sequence for the synthesis of tetrahydrospiro[isobenzofuran‐pyran] derivatives 48 through coupling between 3‐[2‐(hydroxymethyl)phenyl]but‐3‐en‐1‐ol ( 46 ) and carbonyl compounds 47 (Scheme ) . Spirocyclization between 46 and benzaldehyde in the presence of In(OTf) 3 at 80 °C furnished the desired product with high selectivity (96:4).…”

Preparation of trans-2-Substituted-4-halopiperidines and cis-2-Substituted-4-halotetrahydropyrans via AlCl3-Catalyzed Prins Reaction

“…Of the variety of methods developed, Prins-type cyclization of homoallylic amines/alcohols with carbonyl compounds would be one of the most attractive strategies for the formation of these heterocycles. Since the first publication of H 2 SO 4 -mediated addition of formaldehyde to alkenes by Prins, considerable work has been carried out to expand the application scope of this transformation: different Brønsted and Lewis acids such as TfOH, p -TSA, TFA, HF, BF 3 , FeX 3 , Sc­(OTf) 3 , Ga­(III), In­(III), I 2 , Au­(I), and TMSOTf have been successfully applied in Prins-type cyclization reactions. Further, Prins reactions have also been used as key steps for the syntheses of an increasing number of natural products .…”