Furo[2,3‐c]pyrans from a Vinyl Sulfone Modified Methyl 2,6‐O‐Anhydro‐α‐D‐hexopyranoside: An Experimental and Theoretical Investigation

Abstract

A vinyl sulfone modified bicyclic sugar molecule undergoes efficient Michael addition of hetero‐ and carbon nucleophiles to afford single diastereomers. The same molecule consisting of two other masked functional groups, namely an aldehyde and an oxocarbonium ion, turned out to be a unique synthetic intermediate. The adducts generated from this Michael acceptor and a series of β‐dicarbonyl compounds and related reagents after acid treatment afforded a new class of furo[2,3‐c]pyrans, forming up to three new bonds and three stereocenters. In‐built chirality centers of the sugar derivative controlled the diastereoselectivity of formation of all new bonds without the requirement for any external reagent for asymmetric induction. DFT calculations revealed the formation of furopyrans as the only possible products, which corroborates the experimentally observed results.

Michael Acceptor, Masked Aldehyde and Leaving Group in a Single Intermediate: Unorthodox Approach to Enantiopure Saturated Aza-Heterocycles from a Multifunctional Glyco-Substrate

“…Although 11 and 12 were the expected products, the formation of a C2‐C3 double bond by the cleavage of C2‐N bond indicated that under “certain” reaction conditions the C2‐N bond of 10 would also act as a leaving group. This observation was significantly different from the reaction pattern of the oxo‐analogue 1 a (Scheme ) and prompted us to have a relook at the strategy. Therefore, in addition to the expected route indicated in scheme 2 (cleavage of C5‐O bond), another pathway, namely C2‐N bond cleavage is proposed (Figure ).…”

“…Interestingly, when compounds 14 b ‐ c were treated with much stronger triflic acid (TfOH; pKa=‐14) instead of TFA (pKa=0.23), yet another new class of aza‐tricyclic derivatives 17b–c was obtained in moderate yields along with 10–12 % of 16b–c as side‐products (Scheme ). The identities of furopiperidine derivatives 16a–c were determined by comparing their spectral data with those of furopyrans [Scheme ; 2 a : Y=Me (4 a) or OMe (4 b) or OEt (4 c) ] . In 1 H‐NMR spectra aldehydic, vinylic and methine protons of furopyrans and furopiperidines resonated at comparable regions (see SI; Table S1).…”

“…However, two other related Michael adducts 14e–f on TFA treatment afforded yet another class of complex oxa‐aza tricyclic derivatives 21e–f in good yields. The intramolecular nucleophilic attack occurs at the C1 of oxocarbonium ion intermediate of 14 e’/14 f’ by the keto‐oxygen of C(O)CH 3 residue and the reaction stops at this stage (Scheme ) . We presume that the cyclic structure of the diketones dictated the course of the reaction.…”

“…This trifunctionalized substrate was reacted with the fourth component, a series of 1,3‐dicarbonyl compounds, which attacked the electron deficient vinyl sulfone bond in a Michael fashion. The product thus obtained was treated with acid to generate the aldehyde functionality; two intramolecular reactions, e. g. acetal formation and nucleophilic displacement afforded furo[2,3‐ c ]pyran derivatives 2 a (Scheme ) with complete stereocontrol which was unprecedented in literature …”

“…Deviating from the well chartered strategy of using only anomeric carbon of carbohydrates, we earlier proposed a concept of using a bicyclic derivative, vinyl sulfone‐modified methyl 2,6‐ O ‐anhydro‐α‐D‐hexopyranoside 1 a having an electron‐deficient double bond, a masked aldehyde function (anomeric carbon) and a leaving group at a well‐defined position of a single molecule . This trifunctionalized substrate was reacted with the fourth component, a series of 1,3‐dicarbonyl compounds, which attacked the electron deficient vinyl sulfone bond in a Michael fashion.…”