Efficient and regioselective synthesis of γ-lactone glycosides through a novel debenzylative cyclization reaction

Abstract

An efficient and regioselective approach for the construction of synthetically important γ-lactone glycosides is reported from unprotected aldoses through a new debenzylative lactonization (DBL) reaction. The scope and limitations of this DBL reaction are described starting from a series of commercially available hexoses (l-fucose, d-galactose, d-glucose) and pentoses (d-arabinose, d-ribose, d-lyxose, d-xylose) to afford the corresponding γ-lactones in good yields and without concomitant δ-lactone formation.

Regioselective Synthesis of Difluorinated C-Furanosides Involving a Debenzylative Cycloetherification

“…This regioselectivity comes from a remarkable conformation of an acyclic substrate properly positioning the δ-benzyloxy group for an S N reaction (Figure ). Inspired by the unique properties of this reaction, we recently developed an efficient and regioselective strategy for the preparation of γ-lactone glycosides involving an original debenzylative lactonization (DBL) . To the best of our knowledge, the DBCE reaction has never previously been used to produce fluorinated C -glycosides.…”

“…However, the cyclization of epimer (R)-3g failed, thus showing again that the relative configuration of the CF 2 CO 2 Et and the benzyl group at C-2 strongly influences the reactivity of the starting alcohol. As expected, 25 both diastereoisomers of D-mannose (R)-3h and (S)-3h did not undergo DBCE reaction. Indeed, this lack of reactivity has been explained by an unfavorable "cis" relationship between all substituents of the furan ring, in the oxonium intermediates.…”

“…The main synthetic approaches giving access to tetrahydrofuran derivatives through a debenzylative cycloetherification reaction (DBCE) have been reviewed recently. − Compared to classical C -glycosylation reactions, this cyclization is usually more efficient for the preparation of C -furanosides like C -vinylfuranosides especially because it does not require selective protection/deprotection steps, which can often be cumbersome . This cyclization occurs when an activated alcohol is placed in the δ position of a benzyloxy group and gives regio- and stereoselectively tetrahydrofurans at the expense of a pyran form.…”

“…Indeed, this lack of reactivity has been explained by an unfavorable “ cis ” relationship between all substituents of the furan ring, in the oxonium intermediates. The specific behavior of d -mannose derivatives toward debenzylative cyclizations has already been observed by Nicotra and our group. , The structures of 5a–g have been fully demonstrated using literature data analysis and NMR spectroscopy ( 1 H, 13 C, 19 F, COSY, HSQC, and HMBC). The pyran structure has been ruled out by HMBC NMR experiments in which a spatial coupling could be observed between H-5 and a benzylic carbon.…”

“…Inspired by the unique properties of this reaction, we recently developed an efficient and regioselective strategy for the preparation of γ-lactone glycosides involving an original debenzylative lactonization (DBL). 25 To the best of our knowledge, the DBCE reaction has never previously been used to produce fluorinated C-glycosides. However, it is worth mentioning that the O'Hagan group described a deoxofluormediated DBCE reaction on an α,β,δ-trifluorinated substrate that was a undesired but high-yield (94%) transformation.…”