Synthesis of 25-hydroxyprovitamin D-3 from ergosterol: A mild method for the cleavage of hetero Diels-Alder adducts leading to steroidal 5,7-dienes

A new efficient seven-step procedure is described for the preparation of 3 beta,25-dihydroxy-cholesta-5,7-diene (7) from ergosterol (1) in a total yie ld of 30%. The 3-hydroxy function of ergosterol (1) is protected as tert-bu tyldimethylsilyl ether and the 5,7-diene system as hetero Diels-Alder adduc t with 1,4-dihydrophthalazine-1,4-dione before ozonization of the side chai n double bond. The key step of this synthesis is a very mild method for the cleavage of the hetero Diels-Alder adduct 5 using lithium naphthalenide. T osylation of the 22-hydroxy function, C-C coupling with a C-5 copper reagen t and desilylation in usual way furnished the title compound 7.