Stereocontrol in diels—alder cycloaddition to unsaturated sugars: reactivities of cis-dienophiles with cyclopentadiene

Abstract

Cycloaddition of cyclopentadiene with a d-arabinose-derived cis-dienophile, methyl ( Z)-4,5,6,7-tetra- O-acetyl-2,32-dideoxy- d- arabino-hept-2-enonate ( 2), under thermal conditions gave essentially a single norbornene aduct, isolated crystaline in 81% yield and identified by NMR spectroscopy and X-ray crystallography as methyl ( 5R,6S)-6- endo-(1,2,3,4-tetra- O-acetyl- d- arabino-tetritol-1-yl) bicyclo[2.2.1]-hept-2-ene-5- endo-carboxylate ( 3). The diene adds exclusively from the si-face of the dienophile and give only the endo product. The same sequence starting from l-arabinose gave the enantiomer ( 7) of 3. In contrast, a related cis-dienophile ( 9) having a butenolide ring with cyclopentadiene from the opposite ( re) face giving mainly the endo adduct (5S,6R)-6- endo-(2,3,4-tri- O-acetyl)- d- arabino-tetritol-1-yl) bicyclo[2.2.1]hept-2-ene-5- endo-carboxylic acid 1,4-lactone ( 10), isolated crystalline in 70% yield, whose structure was again established by NMR spectroscopy, and firmly consolidated by X-ray crystallography. The minor (11%) product was the exo(5S,6R)isomer 11. A cis-enonate 14, analogous to 2 but deoxygenated at the allylic position, showed negligible diastereofacial selectivity ans reacted with cyclopentadiene to give a mixture of all four possible adducts. A 6-membered ring dienophile 16 was also subjected to the same cycloaddition for comparison with the butenolide 9; it gave principally the two endo products 17 and 19 in 31 and 38% yields, respectively, accompanied by 12% of a mixture of the two exo products ( 18 and 20). The quantitative distribution of cycloaddition products as a function of dienophile stereochemistry is discussed. The high degree of asymmetric induction observed, especially with the readily accesible dienophiles 2 and 7, providesa valuable route of access to enantiomerically pure tetra- C-substituted cycloalkanes.