Permanganate Oxidation Revisited: Synthesis of 3‐Deoxy‐2‐uloses via Indium‐Mediated Chain Elongation of Carbohydrates

Abstract

Application of the Barbier‐type indium‐mediated allylation method to suitable substrates offers access to carbohydrates bearing a terminal olefin moiety. The C–C bond forming reaction generates a defined stereochemistry of the new chiral center and tolerates a wide variety of starting aldehydes thus allowing modifications in the carbohydrate backbone. Further transformations of the alkene moiety via an environmentally benign and subtle controlled protocol using potassium permanganate gives rise to the structural motif of 3‐deoxy‐2‐uloses in good yields. The final part of the reaction sequence focuses on the deprotection of the acetyl groups essential for the success of the oxidation step. The acidic and labile 3‐deoxy position of the target molecule is prone to elimination applying standard deacetylation conditions and therefore demands derivatisation of the molecule. The introduction of a thioketal moiety using microwave conditions shows promising results and subsequent standard transformations are applicable leading to the desired products.

Synthesis of 3-deoxy-2-uloses via the indium-mediated allylation reaction

“…Per-O-acetylation facilitated epimer separation via column chromatography. Zemplén saponification provided 2,3-dideoxy-2-C-methylidene-d-gluco-octitol (24). The stereochemical relation between the initial α-substituent and the newly formed hydroxyl group of compound 24 has been confirmed by X-ray analysis (Fig.…”

“…Hence, a thioketal moiety was introduced at position C-2 to give 11 and enabled de-O-acetylation to 12. Final removal of the thioketal yielded 3-deoxy-2-ulose 13 [24]. Herein, we report a novel approach towards 3-deoxy-2-uloses by elongating selected aldoses using 2-(bromomethyl)prop-2-en-1-ol (14) in an indium-mediated allylation reaction.…”

Modular Synthesis of Dihydroxyacetone Monoalkyl Ethers and Isosteric 1‐Hydroxy‐2‐alkanones

“…The ketohydroxylation of alkenes 14 by stoichiometric quantities of KMnO 4 in aqueous acetone under acidic conditions is the oldest methodology,18a but the oxidant remains attractive even at the industrial scale because of its low cost, tolerance to wet media, and environmentally benign character 24. Recent optimization studies indicate that pH control is the key to reaction selectivity for suppression of over‐oxidation 18b. Indeed, this method proved to reliably generate the desired ketols with high selectivity (Scheme ), and low effort, particularly for alkenes having low volatility.…”

Synthesis of 3-Deoxy-l-ketohexoses through Group Transfer

“…Successful removal of the benzoyl protecting groups generated compound 15 , which is an important building block for sugar dithiolacetal chemistry . The dithiane protecting group was removed by treatment with NBS in THF/H 2 O solution to give the free 3-deoxy- l -fructose in six steps in a total yield of 42%. This synthetic approach represents one of the most efficient methods for the synthesis of rare deoxy- l -sugars and represents a practical procedure for the synthesis of 3-deoxy- l -ketohexoses .…”

“…Since l -sorbose is a crucial starting material for the production of vitamin C and a key precursor for the synthesis of a variety of potent glycosidase inhibitors, this sugar synthon 19 could be a building block for synthetic applications in numerous research areas. To generate 3-deoxy- l -sorbose, compound 19 was treated with NBS in THF/H 2 O solution to give the desired product in five steps in a total yield of 32%. To the best of our knowledge, the synthesis of 3-deoxy- l -sorbose was successfully developed.…”