Cation-olefin cyclization

The tricyclic fragrances of cedar wood, cedrene and cedrol, were synthesized by several routes involving cation-olefin cyclization. 

The first synthesis of a P-amyrin derivative was accomplished by a convergent route which depended on cation-olefin cyclization to form the critical central ring. The plan of synthesis was largely guided by the selection of SM goals for the A/B and E ring portions of the target. 

Pentacyclosqualene, the symmetrical hydropicene corresponding to squalene, has not been made by acid-induced cation-olefin cyclization of squalene, despite considerable experimental study. A simple, convergent synthesis of pentacyclosqualene using cation-olefin cyclization to generate ring C was developed. The Cjo-framework was constructed by radical coupling to a tetracyclic intermediate that was also used for the synthesis of onoceradiene. 

The Shapiro reaction provides a convenient, easy and straightforward method to convert ketones into a plethora of olefinic substances in high yields. Many of these vinyllithium derivatives are useful for further synthetic manipulations. No attempt is made in this chapter to cover all the applications of the Shapiro reaction and only few representative examples will be described. A variety of polyolefins such as 119, used for cation olefin cyclization, can be stereospecifically formed in a concise and modular approach in a single step from the components shown in equation 42 via the Shapiro reaction . 

Scheme 4.17. Two cation-olefin cyclization events to afford an aromatic indane.

Cationic olefin cyclization of aldehyde enol acetates.1 The enol acetate (2) of citronellal (1) undergoes cyclization to dihydrocyclocitral (3) in the presence of... 

Cationic olefin cyclization as a key step led to the shortest racemic dendrobine synthesis reported so far (163, 164). Livinghouse et al. used an intramolecular acylnitrilium attack on a preformed methylcyclopentene moiety to construct the quaternary center and a reductive radical cyclization as second key step in a convergent synthesis to construct the fully substituted skeleton of dendrobine. A few additional steps led then to dendrobine (82). In most of the syntheses following Livinghouse efforts the intention was less focused on strategy (economy) of the synthesis of dendrobine (82) than on demonstrating the versatility of the (newly developed) key step. 

Type-Ill cyclizations are initiated by conversion of an acetal, ketal or enol ether into an oxonium ion. Such an activated carbonyl group attacks an olefin intramolecularly in an exo reaction. Mono- and trialkylated double bonds form new C-C bonds regioselectively at the least hindered terminus according to Markovnikov s rule, and in this case endo cyclization products can be produced25. It is worth noting that acetals are also used as initiators in cation olefin cyclizations (see Section 1.5.5.3.)26. Use of activated acetals in Lewis acid catalyzed C-glycoside synthesis is also known 12c 12e. 

Formation of six-membered rings is the most common process in cation olefin cyclization. The initial cation is attacked by an olefin following Markovnikov s rule. Defined chairlike conformations in the transition state and the validity of the Stork Eschenmoser postulate9 allows the prediction of stereochemistry in a significant number of the cyclization products. 

Starting from tetrahydrocyclopenta[f)]furan-2-one 342, enyne 343, the substrate for the domino reaction, was prepared in 12 steps and with an overall yield of 45%. Exposure of 343 to the electron-rich gold(I) complex (t-Bu)2P(o-biphenyl)AuCl at room temperature afforded cis-hydrindanone 344 in 78% yield as a single stereoisomer (Scheme 14.54). The postulated mechanism involved Au(I) activation of the alkyne to initiate the cationic olefin cyclization of 346 to give carbocation 347, which then underwent a pinacol rearrangement to the final product 344. An originally attempted Lewis acid-catalyzed domino Prins/pinacol rearrangement of... 

Allyl alcohols have often proved to be excellent initiators in cation-olefin cyclizations and this is once again demonstrated by the clean conversion of nerol (183) into (184) and of (185) into (186) brought about by a titanium tetrahalide-A-methylaniline combination, In contrast, thallic perchlorate converts (183) into (187), indicating that initiation of cyclization had been induced by attack of... 

Johnson and his collaborators have continued to refine their excellent procedures for steroid synthesis via cation-olefin cyclization. Their recent investiga-tions (Scheme 13) demonstrate that styrenes are superior to phenyl-acetylenes as terminators since the overall reaction is much more stereoselective. In addition, incorporation of an internal nucleophile into the styryl terminator greatly reduces the formation of undesired by-products. 

Johnson and his co-workers have published full details of their synthesis of the steroid nucleus via cation-olefin cyclization using methylacetylene as... 

Thus, one equivalent of dimethylaluminium chloride has been shown to result in an ene reaction to give the alcohol (46), compared to the use of two equivalents, which produces complex mixtures by means of cation-olefin cyclizations. ... 

Natural product structures often elicit biomimetic reasoning that leads to mechanistic hypotheses for new reaction processes. Two notable examples of syntheses that capitalized on snch thinking are the progesterone 128) and homosecodaphniphyllate 129) syntheses highlighted in Figure 22. The cation-olefin cyclization used by William S. Johnson drew its inspiration from the Stork-Eschemnoser hypothesis 130,131,132) for enzymatic squalene... 

An ingenious new approach to estrone, by Bartlett and Johnson, based on a highly efficient stereospecific cationic olefinic cyclization is outlined below. 

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