Acid-catalysed cyclization

Finally, in a study of Lewis-acid-catalysed intramolecular attack of acetals on vinylsilanes, to produce allylically unsaturated oxacyclics, it has been found (75) that the alkene stereochemistry can control the mode of cyclization in an exo- or endocyclic sense, as shown here ... 

A seven-membered ring is formed in the cyclization of 195 (equation 95)105. The homologue 196 affords the fused cyclooctane 197, together with the cis- and trans-decalinones 198 (equation 96)106. Six-, seven- and eight-membered rings are produced in Lewis acid-catalysed reactions of various cyclohexenones with side-chains terminating in allylic trimethylsilyl groups (equations 97 - 99)107. 

Theoretical evidence [Hartree-Fock (RHF) calculations and density functional theory] has been obtained for a concerted mechanism of oxirane cleavage and A-ring formation in oxidosqualene cyclization. A common concerted mechanistic pathway has been demonstrated for the acid-catalysed cyclization of 5,6-unsaturated oxiranes in chemical and enzymic systems. For example, the conversion of (24) into (26) proceeds via (25) and not via a discrete carbocation (27). Kinetic studies and other evidence are presented for various systems. 

The acid-catalysed transannular cyclization of 8-10-membered y,5-unsaturated cyclic sulfides (59) or (60) yields c/x-fused bicyclic sulfonium salts (61) independently of the geometry of the double bond. The rate varies linearly with the acidity function -(Ho h with a slope of 1. The rate variations span a range of about 10 , the maximum rate difference being observed for the ( /Z)-thiacyclooct-4-ene pair. The data are consistent with the classical interpretation of the intramolecular reactivity in terms of internal strain of the substrate and/or of the transition state. ... 

A detailed mechanistic study of acid-catalysed monocyclization of 5,6-unsaturated epoxides, such as (66), has now provided compelling evidence for a pathway in which the oxirane C—O cleavage and the C—C bond formation are concerted. These experimental results are now further supported by theoretical evidence for a concerted mechanism of the oxirane cleavage and A-ring formation in epoxysqualene cyclisation, obtained at the RHF/6-31G and B3LYP/6-31 + G levels. The chemical pathway thus parallels the mechanism of the enzymatic cyclization that plays a role in the biosynthesis of isoprenoids. 

The electrochemical cyclization of enol ethers in methanol uses an undivided cell and 2,6-lutidine is added as a proton scavenger. Acid catalysed hydrolysis of the enol function is thus avoided. An advantage is gained by diluting the methanol witli a non-nucleophilic co-solvent. This lowers the extent of dimethoxylation of... 

Aminothiazolines are usually prepared by the acid catalysed cyclization of AT-(2-hydroxyethyl)thioureas or the cyclization of the hydrogen sulfate of thioureas in aqueous basic conditions. These methods give low yields of 2-aminothiazolines and are not suitable for acid sensitive or racemization prone substrates. Mitsunobu reaction of thioureas such as 33 afforded 2-methylaminothiazolines 34 in good to excellent yields <99TL3125>. 

Pictet-Spengler synthesis is another method of preparing isoquinolines. (3-phenylethylamine reacts with an aldehyde to produce an imine, which undergoes acid-catalysed cyclization, resulting in the synthesis of the tetrahydroisoquinoline system. Again, tetrahydroisoquinoline can he aromatized hy palladium dehydrogenation to produce an isoquinoline system. 

Squalene is an important biological precursor of many triterpenoids, one of which is cholesterol. The first step in the conversion of squalene to lanosterol is epoxidation of the 2,3-douhle bond of squalene. Acid-catalysed ring opening of the epoxide initiates a series of cyclizations, resulting in the formation of protesterol cation. Elimination of a C-9 proton leads to the 1,2-hydride and 1,2-methyl shifts, resulting in the formation of lanosterol, which in turn converted to cholesterol by enzymes in a series of 19 steps. 

Trimethoxydiazoacetophenone undergoes acid-catalysed cyclization to give 4,6 - dimetho xy- 3 (2H) -ben zo fu rano ne.5 7 Under the same conditions diazoacetophenone gives tlie intermolecular product 2-hydroxyacetophenone. The difference in reaction mechanism was attributed to the interaction of o-OMe with the diazomethyl group. 

A previously proposed mechanism for the acid-catalysed cyclization of 5-cyclodecynone (268) to 272 that involved hydration of the intermediate vinyl cation (269 — 270) has now been ruled out, since no significant incorporation of 180 could be observed when the reaction was carried out in H2180. Instead, a new mechanism has been proposed, involving the cyclization of 269 to 271 followed by fragmentation of the C—O bond396. 

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