Cyclic hemiacetals formation

Aldoses incorporate two functional groups C=0 and OH which are capable of react mg with each other We saw m Section 17 8 that nucleophilic addition of an alcohol function to a carbonyl group gives a hemiacetal When the hydroxyl and carbonyl groups are part of the same molecule a cyclic hemiacetal results as illustrated m Figure 25 3 Cyclic hemiacetal formation is most common when the ring that results is five or SIX membered Five membered cyclic hemiacetals of carbohydrates are called furanose forms SIX membered ones are called pyranose forms The nng carbon that is derived... 

FIGURE 25 3 Cyclic hemiacetal formation in 4 hydroxybutanal and 5 hydroxypentanal... 

Aldoses exist almost exclusively as their cyclic hemiacetals very little of the open chain form is present at equilibrium To understand their structures and chemical reac tions we need to be able to translate Fischer projections of carbohydrates into their cyclic hemiacetal forms Consider first cyclic hemiacetal formation m d erythrose To visualize furanose nng formation more clearly redraw the Fischer projection m a form more suited to cyclization being careful to maintain the stereochemistry at each chirality center... 

Furanose form (Section 25 6) Five membered nng ansing via cyclic hemiacetal formation between the carbonyl group and a hydroxyl group of a carbohydrate... 

Cyclic hemiacetal formation between the carbonyl group and the C-4 hydroxyl yields the a- and jS-furanose forms of D-arabinose. 

Addition to the Carbonyl Group — The internal, cyclic hemiacetal formation is one of the illustrations of such addition. The H2N-X nucleophiles, with X being NH2 (hydrazine), NHAr (arylhydrazines), OH (hydroxylamine), NHCONH2 (semi-carbazide), NHCSNH2 (thiosemicarbazide), or alkyl (primary amine), produce hydrazones, arylhydrazones, oximes, semicarbazones, thiosemicarbazones, and alkyl imines (Schiff bases), respectively, following the following path 5.4 + 5.15 — 5.16 ->. .. -> 5.21. 

Aldol condensation between a 1,3-dicarbonyl component and a ketone with an a-methylene, under acidic, dehydrating conditions, prodnces pyrylinm salts.It is likely that the initial condensation is followed by a dehydration before the cyclic hemiacetal formation and loss of a second water molecule. The use of the bis-acetal of malondialdehyde, as a synthon for malondialdehyde, is one of the few ways available for preparing a-unsubstitnted pyrylinms. ... 

It had now become clear that if we wished to successfully methylenate the C(l)-carbonyl of 40, we would have to prevent cyclic hemiacetal formation from occurring. A synthetic retreat was therefore beaten, and a triethylsilyl (TES) group was positioned on the C(4)-OH of 63 (Scheme 15). Nucleophilic displacement of the tosyloxy unit now afforded the iodopyranoside 65, and Vasella reductive ring cleavage delivered the desired aldehyde 66 in 85% yield. 

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