The Tishchenko reaction [1] (discovered by Claisen [2] in 1887) is the disproportionation of two aldehyde molecules to furnish an ester product (Scheme 1).[3] Aluminum alkoxides [1,4] and boric acid, [5] were the first classes of synthetically relevant homogeneous catalysts [6] for this reaction, these were then followed by a range of transition-metal complexes of low to high catalytic activity but often limited practical utility. [7,8] More recently, lanthanide, [9] actinide, [10] and calcium [11] complexes capable of promoting aldehyde dimerization with excellent activity have been reported. A generalized mechanistic outline of the process is given in Scheme 1: reaction of the transition-metal complex 1 with the aldehyde generates the metal alkoxide 2, which acts as the hydride-transfer agent in a metal-mediated redox process (i.e. 3) leading to ester 4.[12]The Tishchenko reaction is an unusual process from a mechanistic standpoint with the potential to allow chemists to plan the synthesis of ester products through an unconventional disconnection. While recent advances in catalyst development have resulted in increased promise as a general synthetic methodology, the utility of the Tishchenko reaction is somewhat limited by two factors: a) Often the reported catalyst systems result in lower yields of isolated products from substituted benzaldehydes, and b) intermolecular crossed-Tishchenko reactions between equimolar amounts of two different carbonyl moieties are generally not possible. In particular no examples of intermolecular cross-coupling [13,14] between an aldehyde and a ketone are known, meaning that the intermolecular reaction cannot currently be utilized to generate new stereogenic centers. We were therefore encouraged to attempt the development of an alternative catalyst system for the intermolecular Tishchenko process. Our objective was to devise a simple, inexpensive, and easy to use small-molecule promoter, the steric and electronic characteristics of which could be readily tuned, with the eventual goal of broadening the scope of the Tishchenko reaction to include ketone substrates. We were inspired by the mode of action of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (G3PDHase), which promotes aldehyde oxidation through base-catalyzed addition of a cysteine residue to the aldehyde substrate to give the corresponding hemithioacetal conjugate base 5 (Scheme 2, A), which participates in an intermolecular hydride-transfer reaction with enzyme-bound NAD + . The resulting electrophilic thioester 6 then undergoes either hydrolysis or substitution by inorganic phosphate (depending on the enzyme variant). [15][16][17] We postulated the viability of an artificial process in which an analogous hemithioacetal anion 9 generated from benzaldehyde (8) and a bromomagnesium thiolate [18] could transfer hydride [19,20] to another carbonyl moiety to give magnesium alkoxide 10 and thioester 11, [21] which would subsequently couple to form the ester product 12 with regeneration of the thiolate catal...

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The work described deals with the isolation and characterization of epoxides from 6-deoxyhex-5-enopyranosides and preliminary exploration of their synthetic potential. Prolonged epoxidation reaction times led to their hydrolysis in situ and gave novel protected D-hexos-5-ulose derivatives (sugar 1,5-dicarbonyls). Some reactions of the hexos-5-uloses were studied, and in some cases septanoside (seven-membered-ring saccharide) derivatives were isolated. Novel routes to D-xylo-hexos-5-ulose and D-lyxo-hexos-5-ulose, of interest as intermediates in the synthesis and biosynthesis of inositols and aza sugars, are also described. The structures of the epoxides and novel hexos-5-uloses were established by NMR and X-ray crystallographic methods.

1-Deoxynojirimycin, 1-deoxymannojirimycin, and 1-deoxygalactostatin have been synthesized by epoxidation of tri-O-acetyl-6-deoxyhex-5-enopyranosyl azides followed by methanolysis, deacetylation, and catalytic hydrogenation. 1,6-Dideoxygalactostatin was obtained by the reaction of 2,3,4-tri-O-acetyl-6-deoxy-beta-L-arabino-hex-5-enopyranosyl azide with NIS in methanol followed by deacetylation and catalytic hydrogenation. The overall yields were 4.4-23.5% over seven to nine steps.

[reaction: see text] Polyhydroxylated indolizidines have potential for treatment of HIV, hepatitis C and HSV infection, multiple sclerosis, angiogenesis, cancer, and diabetes. A new synthetic approach to the title compounds from a 5-C-methoxypyranosyl azide has been developed. The route incorporates the aldol reaction and a novel catalytic reductive amination cascade to generate the indolizidine ring.