Stereoselective dienyl ether syntheses from malonaldehyde trans-enol ethers: (E)-buta-1,3-dienyl, and (E,Z)- and (E,E)-4-chlorobuta-1,3-dienyl ethers of a protected sugar; conversion of the latter into functionalized chiral disaccharide precursors

Abstract

Condensation of the enol tosylate of malonaldehyde with the sodium alcoholate NaOR derived from ‘diacetone glucose’ gave in 92% yield the almost pure trans-enol ether RO–CHCH–CHO (1). This could be readily condensed with suitable Wittig phosphoranes to give either the buta-1,3-dienyl ether (2)(87% yield; more than 90%trans), or a mixture of 4-chlorobuta-1,3-dienyl ethers (85%) of ‘diacetone glucose;’ the main components were the (E,Z)-diene (5)(45%) and the (E,E)-diene (4)(45%). Cycloaddition of diethyl mesoxalate to the diene (4) gave a mixture of two 3-chloro-2, 2-bisethoxycarbonyl-3,6-dihydro-2H-pyran-6-yl ethers, the (3S,6S)-derivative (6)(69%) and the (3R,6R)-derivative (7)(19%). Free-radical reduction of these chlorides (6) and (7) with tributylstannane led to mainly rearranged products: the 2, 2-bisethoxycarbonyl-5, 6-dihydro-2H-pyran-6-yl ethers, (6S)(9) and (6R)(11). In the same way, nucleophilic substitution of the chloride (6) with azide led to the (5S)-5-azido-derivative (12) of the dihydropyran (9). Catalytic reduction of the double bond and the azido group in (12), followed by N-acetylation, gave the saturated (S)-acetamido derivative (13), which could be deethoxycarbonylated to give two disaccharides with a 2-acetamido-2-deoxyhexopyranosyl non-reducing unit. We consider that the above overall sequence of reactions is a useful extension of the cycloaddition method of disaccharide synthesis.