Transformation of d-Glucose into 1D-3-Deoxy-3-hydroxymethyl-myo-inositol by Stereocontrolled Intramolecular Henry Reaction

Abstract

[reaction: see text] An intramolecular Henry cyclization provides a promising new strategy for the transformation of nitroheptofuranoses into deoxyhydroxymethylinositols. This method has allowed a stereospecific transformation of d-glucose into 1D-3-deoxy-3-hydroxymethyl-myo-inositol.

Synthesis and Conformational and Biological Aspects of Carbasugars

“…More recently, Estévez and co-workers have reported a completely stereoselective intramolecular nitroaldol condensation, using nitroethanol, leading to a 5a-hydroxycarbasugar derivative 1008 (Scheme ) . The authors used two nitroaldol reactions to convert d -glucose derivative 1003 to intermediate 1007 .…”

Recent Advances in the Chemistry of Aminocyclitols

“…The intramolecular version of this reaction has been successfully applied to the elaboration of nitro‐substituted cycloalkanes in the context of the total synthesis of some natural products 50,51. In particular, this reaction has been used in the synthesis of nitrocyclohexanol adducts starting from D ‐glucose52 and also in the synthesis of inositols through subsequent removal of the nitro group under radical conditions ( n ‐Bu 3 SnH/AIBN) 53. For a chemoenzymatic version of this reaction and applications to the synthesis of aminocyclitols, see Section 3 and Scheme .…”

Aza‐Henry Reaction with Nitrones, an Under‐Explored Transformation

“…Due to its peculiar basicity in non‐aqueous solvents, fluoride anion is a good alternative for the removal of C–H acidic hydrogens in aprotic solvents . Ammonium fluorides have notably been used to initiate Henry reaction with sugar‐derived aldehydes and chiral quaternary ammonium fluorides proved their efficiency in enantioselective carbon–carbon bond formation reactions with nitromethane . Hence, when tetramethylammonium fluoride (TMAF) was used as the base (0.25 equivalent) in CH 3 NO 2 as the solvent, conversion reached 66 % and 2‐hydroxy‐1‐nitromethyl‐1,2,3,4‐tetrahydroisoquinoline 4 was isolated in 28 % yield.…”

“…Ammonium fluorides or strong organic bases such as TBD are convenient promoters. Alternatively, phase‐transfer catalysis gave also acceptable yields, which opens the door to various enantioselective strategies of the reaction under kinetic conditions, either with chiral ammonium fluorides,[12b] chiral Brønsted bases or by using cinchona alkaloids as PT catalysts . Nitroethane or nitropropane proved also possible C ‐nucleophiles, affording mixtures of isomerisable β‐alkyl‐β‐nitro‐hydroxylamines.…”