A Cascade “Prins‐Pinacol‐Type Rearrangement and C4‐OBn Participation” on Carbohydrate Substrates: Synthesis of Bridged Tricyclic Ketals, Annulated Sugars and C2‐Branched Heptoses

Abstract

A "Prins pinacol type rearrangement followed by C4-OBn participation" in a cascade manner has been observed while probing the fate of carbocation in some carbohydrate derived homoallylic alcohols in the Prins reaction. This has led to an easy access to tetrahydrofuran-fused bridged bicyclic ketals (or tetrahydrofuran-fused 1,6-anhydro-heptopyranose frameworks) which are further converted into some annulated sugars and C2-branched heptoses.

A Cascade of Prins Reaction and Pinacol‐Type Rearrangement: Access to 2,3‐Dideoxy‐3C‐Formyl β‐C‐Aryl/Alkyl Furanosides and 2‐Deoxy‐2C‐Branched β‐C‐Aryl Furanoside

“…Alternatively, we also expected the Prins‐pinacol type rearrangement to occur with a C–C bond migration once the initial oxocarbenium ion was formed in a typical Prins reaction (vide infra). These were based on our recent experience, and also along a somewhat similar report by Overman et al It was expected to lead to 2,3‐dideoxy‐3C‐formyl β‐ C ‐phenyl furanoside 8a (Table ) in the reaction of 3 with benzaldehyde. The required starting material 5 was prepared from 4 , by a known strategy as shown in Scheme .…”

“…The Prins reaction is a versatile strategy for the construction of a tetrahydropyran/furan ring systems which exist as a core structure in several natural products . In this direction, we recently reported a successful utility of the Prins‐pinacol‐type rearrangement in carbohydrate chemistry involving C‐4‐ O Bn participation on 1,2‐anhydrosugar derived homoallylic alcohols in the synthesis of bridged tricyclic ketals . We also synthesized 2C‐branched C ‐aryl/alkyl glycosides from Perlin‐aldehyde derived substrates through the Prins reaction…”

“…The importance of diversity‐oriented synthesis (DOS) in the development of a small molecular library with potential biological significance through a diversity‐oriented synthesis has attracted much attention . In continuation of our efforts towards the synthesis of C ‐aryl/alkyl glycosides,, , more recently we have reported on the synthesis of a molecular library of 2‐deoxy‐3,4‐fused C ‐aryl/alkyl glycosides through the cascade Prins cyclization of a d ‐mannitol derived homoallylic alcohol . Depending on the protection of the allylic hydroxyl group of such a d ‐mannitol derived homoallylic alcohol, 2‐deoxy‐3,4‐fused sugar scaffolds namely isochroman derivatives, bicyclic vinyl halide derivatives, fluorine substituted tetrahydropyrans and furan derivatives were procured.…”

Stereoselective Synthesis of 1,2‐Annulated Sugars Having Substituted Tetrahydropyran/(‐furan) Scaffolds Using the Prins‐Reaction

“…Recently, in the process of exploring the utility of Prins‐type reactions in carbohydrate chemistry, we reported a cascade Prins‐Pinacol type rearrangement with C4‐OBn participation on carbohydrate substrates, which led to bridged tricyclic ketals, annulated sugars, and C‐2‐branched heptoses. [8a] Furthermore, sequential Prins‐ and Friedel–Crafts cyclizations using a Perlin‐aldehyde derived homo‐allylic alcohol with a variety of aldehydes led to 1C‐Aryl/Alkyl 2C‐branched sugar‐fused isochroman derivatives. [8b] In continuation of our efforts in the synthesis of annulated sugars, it occurred to us that the reaction of a sugar‐derived silylated unsaturated alcohol as well as a homopropargylic alcohol with aldehydes under acid catalysis could give access to sugar‐fused substituted tetrahydropyrans and tetrahydrofurans, respectively.…”

“…[8a] Furthermore, sequential Prins‐ and Friedel–Crafts cyclizations using a Perlin‐aldehyde derived homo‐allylic alcohol with a variety of aldehydes led to 1C‐Aryl/Alkyl 2C‐branched sugar‐fused isochroman derivatives. [8b] In continuation of our efforts in the synthesis of annulated sugars, it occurred to us that the reaction of a sugar‐derived silylated unsaturated alcohol as well as a homopropargylic alcohol with aldehydes under acid catalysis could give access to sugar‐fused substituted tetrahydropyrans and tetrahydrofurans, respectively. Herein, we wish to report the realization of such a strategy for the stereoselective synthesis of 1,2‐annulated sugars having substituted tetrahydropyrans and tetrahydrofurans via silyl‐Prins reaction and alkyne‐Prins reaction, respectively.…”