Alkyl cleavage, regiospecific

An important stage in the synthesis has been reached. It was anticipated that cleavage of the trimethylsilyl enol ether in 18 using the procedure of Binkley and Heathcock18 would regiospecifically furnish the thermodynamic (more substituted) cyclopentanone enolate, a nucleophilic species that could then be alkylated with iodo-diyne 17. To secure what is to become the trans CD ring junction of the steroid nucleus, the diastereoisomer in which the vinyl and methyl substituents have a cis relationship must be formed. In the... 

Another example is the indirect acetonylation of a 1,2,3,4-tetrahydropyridine derivative at the (3-position of the enamide system [99]. The reaction involves a double alkylation to furnish an acetylcyclopropane which undergoes fragmentation on acid treatment. It is noted that polarity alternation and ring strain relief allow the facile and regiospecific C-C bond cleavage to proceed, the intervention of a cyclopropane intermediate also leads to disjoint system. This is a fundamental strategy [100] which has been frequently employed to gain access to compounds with disjoint functionalities. 

Any attempt to present a meaningful mechanistic scheme to describe the excited-state chemistry of cyclobutanone, therefore, must be capable of accounting for (a) the apparent photoreactivity of the state, (b) the regiospecificity of a-cleavage (i.e., that direction which would afford the most stable acyl alkyl biradical intermediate), (c) the apparent stereoselectivity of all reactions, and (d) the inherent inefficiency of all photoreactions, including that for ketone disappearance (see Table III). Consideration of all the available evidence suggests the mechanism set forth in Scheme IV. Excitation (n -> u ) of the ground-state ketone (SQ) initially produces the lowest electronically excited... 

Alkylation of fl-aryleyclopentanones. Addition of 10 mole% of CuCN to the lithium enolate prepared from /3-arylcyclopentanones and LDA increases the amount of the less stable product of alkylation. Polyalkylation is also suppressed. Similar results are obtained when methyl- or phenylcopper is added to the enolate prepared by alkyUithium cleavage of trimethylsilyl enol ethers. The mechanism by which Cu(I) influences these alkylations is not as yet understood. The regiospecificity of enolate formation in the example Illustrated in equation (I) has been attributed to a directing efiect of the proximate phenyl group. This effect is also observed in the deprotonation of -arylcyclohexanones. Quantitative, but not qualitative, differences exist between five- and six-membered rings, probably because of conformational differences. ... 

PotassiumI biphenyl Regiospecific cleavage of alkyl aryl ethers... 

The oxidative cleavage of ethers to give carbonyl compounds has been demonstrated using UFe (readily available deficient in U) as oxidant. The reaction is regiospecific with methyl ethers (89 90). Phenyl thioethers have also been shown to undergo oxidative cleavage via a-chlorination (Scheme 41) giving, as shown, a route from alkenes or alkyl halides to aldehydes. 

A number of 1-substituted cyclopropanols are now available by nucleophilic attack on cyclopropanone, which may be generated in situ from its hemiacetals or other stable precursors. Although the cyclopropanols are obtained in these reactions without ring cleavage, nucleophilk decomposition of JV-alkyl-cyclopropanimine (274) gives a regiospecific C-1—C-3 cleavage (Scheme 41). ... 

Ren R, Zhao H, Huan L, Zhu C (2015) Manganese-catalyzed oxidative azidation of cyclobutanols regiospecific synthesis of alkyl azides by C-C bond cleavage. Angew Chem IntEd 127(43) 12883-12887... 

A full paper has appeared on the use of UFe for the regiospecific oxidative cleavage of alkyl methyl ethers. Oxonium ions are formed as intermediates and these species can be trapped with the appropriate dithiol to give 1,2-dithiolans or 1,3-dithiolans. ... 

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