Synthesis of the C19-C30 bis-THF fragment of iriomoteolide-13a via stepwise SN2 cyclization and intramolecular syn-oxypalladation

The C19-C30 bis-THF fragment of the proposed structure of iriomoteolide-13a has been synthesized. The omega-mesyloxy-substituted stereotetrad possessing three continuous hydroxy groups was generated by an anti-aldol reaction and asymmetric dihydroxylation (AD) as the key steps. Upon heating in pyridine, the stereotetrad underwent an S(N)2 cyclization to form the C19-C22 THF ring chemoselectively. The propargylic alcohol, after cleavage of the C28-OPMB ether, was reduced to the corresponding allylic alcohol with spontaneous removal of the C23-OTBS protecting group. Finally, the ene triol was subjected to the Pd(ii)-catalyzed intramolecular syn-oxypalladation to give the C23-C26 THF ring with a dr value of 86 : 14. It was found that the C21-OH group, which might form a chelated Pd(ii) complex along with the C23-OH group, was tolerated during the syn-oxypalladation process.