Methylcyclopropyl intermediates

Compared with their cationic counterparts, only a few radical rearrangements are fast enough to appear in synthesis. An example is vinyl migration in which a vinyl group migrates via the formation of the methylcyclopropyl intermediate (Scheme 2.12). 

From the dynamic NMR studies it was shown that the activation barrier for the degenerate equilibrium is 7.4 kcalmoT at -112 This activation barrier is similar to those observed for other 1-cyclopropylethyl cations. The l-(c/.s-l,2-dimethylcyclo-propyl)ethyl and l-(2-methylcyclopropyl)ethyl cations 51 and 55 have an activation barrier for the degenerate rearrangement of less than 5 kcalmol The degenerate equilibrium in all these cases may proceed through the substituted cations as intermediates vide suprdf. ... 

The main products in the reaction mixtures of the 2,2-dimethylcyclopropyl ketone 39 and the cis-2-methylcyclopropyl ketone cis-40, respectively, result from C-l-C-2 bond breaking. In contrast, the frartj-2-methylcyclopropyl ketone trans-41 breaks the C-l-C-3 bond. This strongly suggests that steric factors control the direction of cleavage, presumably through asymmetric overlap of the carbonyl 7r-system with one of the cyclopropane bonds 43). In the absence of these steric effects, as in trans-41, the bond that cleaves is the one to give the more thermodynamically stable (= less substituted) carbanion intermediate. 

The rather unusual conversion of an acetonide to an isopropenyl ether was developed to differentiate a terminal acetonide from several internal ones. It was, in turn, converted to the 1-methylcyclopropyl ether that was later cleaved with NBS or The intermediate isopropenyl group can be removed with I2... 

Silverman and Zieske have rationalized how a protein nucleophile other than flavin is involved in MAO inactivation reactions, and why different inactivator compounds specifically react with flavin, protein amino acids, or both (100). Hydrogen atom donation from a cysteine residue to the flavin semiquinone radical would produce a thiyl radical, which could then capture the primary or secondary alkyl radical generated on cyclopropyl ring opening from the amine radical cation of the inactivator. The hydrogen atom abstraction reaction between the flavin and active site amino acid may be an equilibrium process such that either species could be present at any turnover. Hence, a combination of steric constraints and proximity to either the flavin semiquinone radical or the thiol radical will determine the site of adduct formation for a particular inactivator structure. A two-dimensional representation is shown in Scheme 23 (compounds 40-42), which illustrates the proposed equilibrium between the flavin semiquinone radical and amino acid as well as the proposed intermediates for the inactivation of MAO by A-(l-methylcyclopropyl)benzylamine 40 (104), rrradical center relative to the particular protein radical is consistent with proposed site of attachment of inactivator to protein 40 is near the flavin radical, such that exclusive flavin attachment occurs, 41 is positioned closer to the amino... 

Scheme 23. Proposed role of flavin semiquinone radical, amino acid residue, and possible intermediates in the inactivation of MAO by N-(I-methylcyclopropyl)benzylamine (40) (.104), trans-2-phenylcyclopropylamine (41) (i09), and 1-phenylcyclopropylamine (42) (JOO).

On heating the reaction to 0°C the optical activity is lost. More evidence followed in the 1960s. Reaction of the cis-isomer of 2-methylcyclopropyl bromide with sec-butyUithium, again followed by carboxylation with dry ice, yielded cis-2-methylcyclopropylcarboxylic acid. The formation of the trans-isomer would have indicated that the intermediate carbanion was unstable (Scheme 3.39). 

Frey et al. used 1,1-dimethylcyclopropane as a probe. With sMMO from M. richosporium OB3b, this substrate is oxygenated to (1-methylcyclopropyl)methanol, 3-methyl-3-buten-l-ol, and 1-methylcyclobutanol, in the relative yields shown in eq. (14) [76]. The formation of the ring-opened product suggests a mechanism involving some intermediate rather than a concerted mechanism. Formation of 1-methylcyclobutanol is probably via not a radical intermediate but a carbonium cation. A carbon radical formed by the H-abstraction is oxidized to the carbonium cation by one-electron transfer to an electron deficient active species, probably a resultant diiron(III,IV) intermediate. The... 

---