Spirobipyridopyrans and indolinospiropyridopyrans: Synthesis, x-ray crystal structure, separation of enantiomers, and barriers to thermal cleavage ofthe C(sp(3))-O bond

The novel chiral spirobipyridopyrans 1 and 2 were synthesized by the acid c atalyzed aldol type condensation of 5-deoxypyridoxal with the appropriate k etone and subsequent reaction of the resulting pyrylium salt with base. The indolinospiropyridopyrans 3-5, which contain the modified B-6 unit, were p repared by aldol reaction of 5-deoxypyridoxal with 1,3,3-trimethyl-2-methyl enindolines. Analytical separation of enantiomers was accomplished by low-p ressure liquid chromatography (LPLC) on triacetylcellulose. The barriers to thermal racemization were determined by on-line measurements of the enrich ed enantiomers after LPLC. Gibbs energies of activation DeltaG(not equal) f or reversible cleavage of the C-spiro-O bond in 1, 3, and 4 were in the ran ge 103-108 kJ/mol. The lower limits of the barriers in 2 and 5 were estimat ed to be greater than 102 and 109 kJ/mol by attempted thermal racemizations . The increase of the barriers from 3 to 4 and 5 was explained by the influ ence of electron withdrawing groups, which reduce the stability of the ring -opened transition states to C (sp3)-O bond cleavage. Geometrical data from X-ray structure analysis showed that the angle [C3-C2-C3'] around the spir o carbon atom increases with elongation of the chain in the C3-C3' bridge. This angle widening is explained by a ring-strain effect, which is greater in the five-membered ring in the skeleton of 7 than in the six- and seven-m embered rings of 1 and 2, Chirality 13.81-88, 2001. (C) 2001 Wiley-Liss. In c.