Allylic alcohol biomimetic cyclization

Another example is the cyclization of the racemic allylic alcohol 232 at -80°C which furnished the racemic tetracyclic bis-olefin 233 in 70% yield (89, 90). Ozonolysis of 233 gave the bicyclic triketone aldehyde 234 which underwent under acidic conditions a double intramolecular aldol cyclodehydration to produce racemic 16,17-dehydroprogesterone 235. This represents the first synthesis of a steroid via the now so-called "biomimetic" polyene cyclization method. 

The synthesis in Scheme 13.38 combines elements of a biomimetic-type polyene cyclization with a rearrangement similar to that just described in Scheme 13.37. The early stages of the synthesis culminate in the construction of the allylic alcohol in step B. In step C, it is epoxidized using the stereoselective VO(t-BuOOH) method (Section 12.2.1). This epoxidation provides the key intermediate for the polyene cyclization. The mild Lewis acid FeCla is used to promote the cyclization, which terminates in an electrophilic substitution of the methoxyphenyl substituent. Steps E and F convert the methoxyphenyl ring to a diene. This diene undergoes a Diels-Alder reaction in step G. After catalytic reduction of the double bond, the anhydride is subjected to an oxidative bis-decarboxylation (see Section 12.4.2 for discussion of this reaction). The resulting alkene is epoxidized, and the epoxide is reduced. A rearrangement is done at this point. The reaction is similar to that used in Scheme 13.37, except that it involves a saturated, rather than allylic, system. The final steps in the synthesis are those used in Schemes 13.33 and 13.34. 

---