Sugars Knoevenagel reaction

The present review is focused on the Knoevenagel reaction applied to unprotected sugars. It has been divided into two parts (acidic and basic conditions) in which the arguments are treated in chronological order. 

Another route to create a carbon-carbon double bond on a ketosugar is the Knoevenagel reaction and its variants. It has been applied by Szarek and Ali to prepare olefin 133 (Scheme 45) suitable for the formation of a doubly branched-chain sugar [177] [see Section 1I.D]. 

For a recent review on the Knoevenagel reaction of unprotected sugars, see M.-C. Scherrmann, Top. Curr. Chem., 2010, 295, 1. 

The three-component reaction of indole (2) with sugar hydroxyaldehyde 281 and Meldrum s acid 282, with a catalytic amount of D,L-proline, afforded the 3-substitution product 283 as a single isomer [203]. The substituent possesses the czs-fused furo [ 3,2- b ] pyranonc skeleton. The proline catalyzes the Knoevenagel condensation of the sugar aldehyde 281 and Meldrum s acid 282 to provide the alkylidene derivative 284 of Meldrum s acid. Then a diastereo-selective Michael addition of indole and an intramolecular cyclization of this adduct 285 with evolution of carbon dioxide and elimination of acetone furnish the furopyranone in one-pot (Scheme 62). 

Domino Knoevenagel hetero-Diels-Alder reaction of 1 with sugar aldehyde 489 gave, in a stereoselective manner, the fused furo[2, 3 5,6]-pyrano[3,4-c]chromen-l-one 491 presumably via the aldehyde adduct 490 (04TL3493, 04S1150) (Scheme 104). 

A variety of 2-substituted 2//-chromenes can be obtained from the facile reaction of 2-hydroxybenzaldehydes with vinylboronic acids in ionic liquid solvents <04SL2194>. In a one-pot sequence also in an ionic liquid, a Knoevenagel condensation between O-prenylated salicylaldehydes and 4-hydroxycoumarins is followed by an intramolecular hDA reaction to yield ci5-fused chromano[4, 3 4,5]pyrano[3,2-c]coumarins e.g. 20 small amounts of the corresponding chromone are also formed <04S1783>. In like manner, cii-fused furopyranopyran derivatives have been obtained from sugar aldehydes <04TL3493>. 

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