SYNTHESIS OF A C22-34 SUBUNIT OF THE IMMUNOSUPPRESSANT FK-506

A new route to the C22-34 subunit of FK-506 was developed. A highly di astereoselective Diels-Alder reaction of 1,3-butadiene with the bis-ac rylate of (R,R)-hydrobenzoin and subsequent saponification provided th e cyclohexenecarboxylic acid 6.4 of 95% ee. Elaboration to the enal 9. 2 was effected by known transformations. Enal 9.2 underwent diastereos elective and enantiospecific S(E)2' addition of allenyl stannane (S)-3 .9 affording the homopropargylic alcohol 9.3 as an 85:15 syn/anti mixt ure. The PMB ether 9.5 was converted to the known benzylidene derivati ve 10.4 by sequential treatment with Red-Al, epoxidation, a second red uction with Red-Al, and oxidative benzylidene formation with DDQ.