Direct Access to 2,3,4,6-Tetrasubstituted Tetrahydro-2H-pyrans via Tandem S_N2′–Prins Cyclization

Abstract

A new, direct, and diastereoselective synthesis of activated 2,3,4,6-tetrasubstituted tetrahydro-2H-pyrans is described. In this reaction, iron(III) catalyzed an S2'-Prins cyclization tandem process leading to the creation of three new stereocenters in one single step. These activated tetrahydro-2H-pyran units are easily derivatizable through CuAAC conjugations in order to generate multifunctionalized complex molecules. DFT calculations support the in situ S2' reaction as a preliminary step in the Prins cyclization.

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

“…The reaction involves a tandem process via the S N 2′ step, generating the intermediate 4 , and a further Prins cyclization reaction without competitive [3,3]-sigmatropic rearrangement. DFT calculations support the in situ S N 2′ reaction as a preliminary step of the Prins cyclization . The relative syn / anti stereochemistry at the chlorine atom in the starting material is irrelevant to the outcome of the subsequent Prins-cyclization reaction.…”

Novel Position-Specific 18O/16O Measurement of Carbohydrates. II. The Complete Intramolecular 18O/16O Profile of the Glucose Unit in a Starch of C4 Origin

“…The Scoccia et al method was followed, with minor modification, to prepare F . Compound E was dissolved in AcOH (0.18 M, aq), and stirred at room temperature for 14 h. The cold (ice bath) reaction mixture was first neutralized with KOH solution and a small amount of Na 2 CO 3 solid, then concentrated under reduced pressure, and finally extracted with DCM and EtOAc.…”

“…Preparation of 1,2-O-Isopropylidene-3-O-methyl-α-D-glucofuranose (3-MethylMAGF, F). The Scoccia et al 10 method was followed, with minor modification, to prepare F. Compound E was dissolved in AcOH (0.18 M, aq), and stirred at room temperature for 14 h. The cold (ice bath) reaction mixture was first neutralized with KOH solution and a small amount of Na 2 CO 3 solid, then concentrated under reduced pressure, and finally extracted with DCM and EtOAc. The combined organic phase was evaporatively dried to give the crude F, as a colorless-yellow oil, which was further purified by column chromatography (hexane/EtOAc, v/v, 10/1) prior to being used for conversion to G.…”

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

“…Our research group has developed synthetic methodologies that were successfully applied in the preparation of several medium size oxacycles. − Moreover, we reported a straightforward method to gain access to cis -disubstituted Δ 4 -unsaturated oxepanes in one step that was supported by the excellent previous work of other authors . Thus, we resolved to apply our experience to the total synthesis of (+)-isolaurepinnacin ( 1 ) and (+)-neoisoprelaurefucin ( 2 ) using a common parallel synthetic strategy (Scheme ).…”