The study of quinone methides generated by silica-supported acids and their [4+2]-Cycloaddition reactionsParatchata Batsomboon
( M.Sc. )
The ortho-quinone methides (o-QMs) are highly reactive and transient intermediates which have been commonly generated by using thermal or base initiation. These intermediates can easily facilitate the construction of chroman systems, a core structure of the flavonoid families, by the hetero-Diels—Alder reactions with the electron donating group (EDG)-bearing dienophiles. However, there are a limited number of reports, using acidic condition to generate o-QMs, because of low yields and poor diasteroselectivity. This problem can be overcome by using silica-immobilized p-TsOH (PTS-Si) in toluene under mild conditions (0°C to rt). Thus, a stable precursor of o-QMs could consist of a protecting group at phenol (MOM ether) with a leaving group at the benzylic position (acetate group). The investigation of substituent pattern on the aromatic ring showed that the combination of bromine and methoxy group gave the highest yields with styrenes to furnish 2-arylchromans. The α,β-disubstituted styrenes were used to investigate the diastereoselectivity between C2-C3 positions and the results showed a good to excellent diastereoselectivity favoring the trans isomers of products in moderate yields, while only indene gave the single isomer favoring the cis isomer of product in moderate to excellent yields. The o-QM precursors with the various substituents at benzylic position were prepared to explore the correlation of electronic effect and diastereoselectivity between C2 and C4. The electronic effect from the para position of the EDG (p-OMe) on aryl substituent could give the moderate to good yields but only with moderate diasteroselectivity favoring cis isomer. On the other hand, the electron withdrawing group (p-OCF3) on aryl substituent could give moderate yields but with excellent diasteroselectivity favoring cis isomer. Moreover, the o-QM precursors with various substituents at the benzylic position and the α,β-disubstituted styrenes were used to investigate the diastereoselectivity between C2-C3-C4 positions, and the results showed that the relative stereochemistry between C2 and C4 still remained cis and between C2 and C3 was dependent on the configuration of dienophiles. Indene furnished predominantly the C2-C3-C4 cis isomers with moderate to high yields, but with excellent diastereoselectivity.