Stereospecific cationic cyclization

In a brilliant series of experiments, Johnson and co-workers have discovered that the treatment of certain polyolefins having trans olefinic bonds in a 1,5-relationship can produce stereospecific, non enzymic, cationic cyclization products with the all-trans configuration. These transformations... 

Trialkylsilyl vinyl ketenes (72) have been shown to react stereoselectively with a-benzotriazolyl organolithium species to give highly substituted cyclopentenones. The selectivity was found to be kinetic, not thermodynamic, in origin. Several possible mechanisms have been proposed (Scheme 10). It has been suggested that the observed stereoselectivity may result from torquoselectivity in a concerted reaction, or from stereospecific conrotatory cyclization of cation (73), formed stereoselectively because of the interaction shown between the electron-withdrawing group Z and the metal ion.75... 

Notice that although there are four asymmetric centers in the molecule, one isomer is formed in 58% yield. This points to a concerted cyclization step in which the stereochemistry incorporated in the C==C double bonds is transferred to the developing asymmetric centers in the product. (This phenomenon is analogous to the well-known stereospecific formation of the steroid skeleton by cationic cyclizations of similar olefinic systems with defined stereochemistry at the C—C double bonds.)... 

The stereospecificity of cyclization of pentadienyl cations 13-15 to the cyclopentenyl cations 16 and 17 in a variety of acidic media has been determined. The data are shown for 99% sulfuric acid at -5°C ... 

Orbital symmetry considerations predict that ring closure of pentadienyl cations, which are 4n systems, should be controtatory. While some pentadienyl cations are sufficiently stable to be observed by NMR in acidic media, they do tend to cyclize to cyclopentenyl cations. The stereospecificity of cyclization of pentadienyl cations 12-14 to the cyclopentenyl cations 15 and 16 in a variety of acidic media has been determined. The data are shown for 99% sulfuric acid at —The observed stereochemical course is predominantly conrotatory, but the reactions are not as stereospecific as the others we have seen. This is attributed to the fact that... 

One early example was reported by Chatteijee in 1979 for stereospecific synthesis of the sesquiterpene isocomene by transannular cationic cyclization. The acid-catalyzed cyclization of epoxide 152 through transannular participation of the remote double bond led to the formation of 153 (Scheme 20.37), which was further transformed to isocomene. The reaction was stereoselective since formation of any other diastereomers will lead to the formation of much strained polycyclic systems with trans-fased cyclopentanes. 

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

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 . 

For H-acid catalysis stereospecifity is lowered and appears to be the same as in the reactions initiated with trifluroacetic acid instead of the ammoniumyl salt. For the cation-radical mechanism the sterically hindered base 2,6-bis(tert-butyl)pyridine does not inhibit the cyclization triarylamine retards this reaction photosensibilized one-electron oxidation of a diene leads to the same products, which are formed in the presence of the ammoniumyl salt. As shown, in the majority of cases only the cation radical chain mechanism of the diene-diene cyclization is feasible (Bauld, Bellville, Harirchian 1987). Meanwhile, cyclodimerizations of 2,4-dimethylpenta-1,3-diene (Gassman Singleton 1984) and 1,4-dimethylcyclohexa-1,3- or -1,4-diene (Davies et al. 1985) proceed through both mechanisms. 

Another effect of the coordination is that the benzylic cation is also stabilized [63]. This stabilization is explained by delocalization of the positive charge due to the interaction of the d-orbital of Cr with the 71-orbital of the benzylic carbon, caused by the coordination of Cr(CO)3. Facile stereospecific Friedel- Crafts-type cyclization of the complex of the optically active benzyl alcohol 248 gave the tetrahydrobenzazepine 249 with retention of the stereochemistry, and the free amine 250 with 98% ee was... 

Electrophilic substitutions of alkenyl-, aryl-, and alkynylsilanes with heteroatom-stabilized cationic carbon species generated by the action of a Lewis or Brpnsted acid (acyl cation, oxocarbenium ion, etc.) provide powerful methods for carbon-carbon bond formation. Particularly, intramolecular reactions of alkenylsilanes with oxocarbenium and iminium ions are very valuable for stereoselective construction of cyclic ether and amine units.21-23 For example, the BFj OEt -promoted reaction of (E)- and (Z)-alkenylsilanes bearing an acetal moiety in the alkenyl ligand gives 2,6-disubstituted dihydropyrans in a stereospecific manner (Scheme l).23 Arylsilanes also can be utilized for a similar cyclization.24... 

Vinyl ethers propagate cationically yielding stereospecific polymers [87, 92]. Itramolecular cyclization is assumed to occur between the growing chain end and the third unit from the end, yielding a six-membered ring. Free rotation of the cationic end is thus prevented, and the orientation of the approching monomer is controlled [93],... 

The formation of these products can be rationalized as shown in equation (46). Thus, upon complexation of Au(I) to the aUcyne in the reacting enyne, an endo cyclization occurs to form a cyclopropyl gold carbene, which can be trapped by a nucleophile. However, the lack of stereospecificity observed in some of these reactions, suggests the formation of open six-membered ring cations as intermediates, which can be intercepted by an O-Boc group.3-Hydroxy-1,5-allenynes react similarly with Pt(II) catalysts. ... 

Stereospecific 2,3-epoxidation of squalene, followed by a nonconcerted carbocationic cyclization and a series of carbocationic rearrangements, forms lanosterol [79-65-0] (77) in the first steps dedicated solely toward steroid synthesis (109,110). Several biomimetic, cationic cydizations to form steroids or steroidlike nuclei have been observed in the laboratory (111), and the total synthesis of lanosterol has been accomplished by a carbocation—olefin cydization route (112). Through a complex series of enzyme-catalyzed reactions, lanosterol is converted to cholesterol (2). Cholesterol is the principal starting material for steroid hormone biosynthesis in animals. The cholesterol biosynthetic pathway is composed of at least 30 enzymatic reactions. Lanosterol and squalene appear to be normal constituents, in trace amounts, in tissues that are actively synthesizing cholesterol. 

These results, taken in conjunction with the cation-induced cyclizations, indicate that C-l-X (X = H or CCI3) and C-5-C-10 bonding are synchronous. Jain and McCloskey have continued their studies on the cyclization of costunolide (237). On the expectation that the hydroxyeudesmanolide (238), the product of stereospecific hydration of costunolide, might be found in Nature they have prepared... 

Trialkylstannyl derivatives readily cyclize to three-membered ring products by replacement of the stannyl group under conditions of 3-stannylalkyl cation formation " . It has been shown that the cyclization proceeds stereospecifically with inversion of configuration at both reaction centers (equation 4) . The precursors for this reaction... 

In summary, the stereochemical course of cation-7t cyclizations is determined by stereoelectronic and conformational effects. Concerted cation-Ti cyclizations usually involve a stereospecific trans-addition (axial attack) of the carbocation to the double bond. This is exemplified by Johnson s biomimetic synthesis ( )-progesterone, which possesses a trans, anti, trans-fused ring system." - ... 

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