Tetrahydropyranyl ether → HCID 131732512, compound

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Reaction Steps

Scheme 5 shows the synthesis of more highly substituted aryl analogs 19. A suitably protected hydroxy aryl bromide (e.g., as an acid-labile tetrahydropyranyl ether that can be deprotected selectively in the presence of an ester) is lithiated (e.g., n-BuLi) and reacted with cyclohexanone bis-tosylate 1 to give the corresponding cyclohexanol bis-tosylate 14. Base-mediated intramolecular reaction of the alcohol with a tosylate of 26 provides the oxabicyclo[2.2.2]tosylate 15 (same 2 steps as in Scheme 1). The tosylate 15 is then converted in the same 3 step sequence as described in Scheme 4 to give the 2-oxy-substituted ester 16. Selective deprotection of the phenol is then achieved under mild acid conditions to give phenol ester 17. The phenol intermediate 17 is then subjected to an O-arylation reaction (e.g., Chan-Lam coupling reaction with aryl boronic acids; examples in Qiao, J. et al., Synthesis, 829 (2011)) to give the aryl ethers 18, followed by ester deprotection to give the corresponding 2-oxy-substituted carboxylic acid analogs 19.

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