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 ω-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 SN2 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.