Polyene acetal tetracyclization

Polyene cyclization in terpene and steroid synthesis is critically dependent on the terminator in order to generate useful functionalities for further modification of the products. Allyl- and propargylsilanes have proven their value in facilitation of the cyclization and generation of an exocyclic methylene and allene, respectively. Thus, a concise approach to albicanyl acetate [126] and the rapid construction of a tetracyclic precursor of steroids [127] are sufficient to demonstrate the concept. Again, a comparison of the substrates with a silyl group with those having a simple alkyl moiety is very enlightening. 

A spectacular example of cationic cyclization is the Johnson polyene cyclization, described in Section 10.8.A. Polyenes such as squalene are expected to assume a steroid-like conformation in the lowest energy form (sec. 1.5.E), based on the biogenetic preparation of cholesterol from squalene. In practice, treatment of polyenes with acid led to a very low yield of tri- or tetracyclic products, giving instead significant amounts of polymeric material. Diligent work over many years prevailed, however, and Johnson solved the many problems (as described in sec. 10.8.A) to make this reaction an excellent and efficient synthetic route to di-, tri-, and tetracyclic molecules. One of the later examples of polyene cyclization uses an allyl silane to quench the cyclization process. A Lewis acid was used to initiate the reaction via reaction with the acetal. Treatment of... 

In related studies designed to ascertain the elfect of a chiral centre remote from the initiating cationic centre on the stereochemical course of the polyene cyclization, Johnson has made the interesting observation that cyclization of (156), containing a pro-C- chiral centre, leads to only the 1 la-substituted diastereoisomer (157) of the tetracyclic product. Similarly, cyclization of the optically active acetal (158) with SnCU gave the axial and equatorial hydroxy-ethers (159) and (160), respectively, both with ca. 92% enantiomeric purity. ... 

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