Abstract
A small library of isochromane-triazole hybrid compounds were synthesised from commercially available 3-hydroxybenzaldehyde in a sequence of 8 steps. O-Allylation, followed by Claisen rearrangement gave a mixture of the regioisomeric products out of which of 2-allyl-3-hydroxy-benzaldehyde was isolated. Protection of its phenolic group as a benzyl ether, nucleophilic addition of methyl magnesium iodide across its aldehyde and Wacker-oxidation mediated pyran ring formation afforded 5-benzyloxyz-1,3-dimethyl-1H-isochromene. The remainder of the mixture of regioisomers 2-allyl-3-hydroxy-benzaldehyde and 4-allyl-3-hydroxy-benzaldehyde was again subjected to O-allylation followed by Claisen rearrangement to afford 2,4-diallyl-3-hydroxy-benzaldehyde which was elaborated into 5-benzyloxy-1,3-dimethyl-6-propenyl-1H-isochromene using the same chemical transformations. Catalytic hydrogenation of 5-benzyloxy-1,3-dimethyl-1H-isochromene with concomitant removal of the benzyl group using Pd/C afforded rac-cis-1,3-dimethyl-isochroman-5-ol, which was then converted into the propargyl ether. Cycloaddition of the methyleneoxy anchored terminal alkyne with a variety of functionalized phenylazides synthesized from the corresponding boronic acids and sodium azide gave the desired isochroman-triazole hybrid compounds in good yields. Attempts to synthesize biaryl isochromane analogues using Suzuki-Miyaura coupling were unsuccessful as the p-toluene- and trifluoromethane-sulfonate esters of 1,3-dimethylisochroman-5-ol failed to undergo coupling. 5-Benzyloxy-1,3-dimethyl-6-propenyl-1H-isochromene also failed to undergo Grubbs generation 2 catalyst-mediated metathesis with a variety of styrenes in another attempt to broaden compound structural diversity.
M.Sc. (Chemistry)