Methylcyclopropyl Radicals

Hunsdiecker reaction of the silver salts of both cis-(56) and trans-2-methylcyclopropanecarboxylic acid (57) yielded the same mixture of cis- (58) and trans-1-bromo-2-methylcyclopropane (59), thus demonstrating that the 2-methylcyclopropyl radical was incapable of maintaining its configuration . Brominative decarboxylation of the silver salts of exo- (60) and em/o-norcarane-7-carboxylic acid (61) produced the same mixture (16 84) of exo- (62) and entio-7-bromonorcarane (63)". Similarly, cis- and trans-silver 1,2-cyclopropanedicarboxylate gave rise to the same isomer ratio (24 76) of cis- and fraws-1,2-dibromocyclopropane. Consistent with these results is the report that the Hunsdiecker reaction with the silver salt of trans-2,2,3-d3-cyclopropanecarboxylic acid (64) gives an equimolar mixture of cis- (65) and rrans-2,2,3-d3-cyclopropane (66) . 

The inversion of the methylcyclopropyl radical, characterized by the same barrier height, becomes thermally activated above 90 K, and its rate constant increases from 3 x 105 to 109 Hz in the range 90-170 K. Quan-... 

Figure 8.5. The methylcyclopropyl radical in various conformations, (a) The non-planar-bisected conformation is stable, (b) The non-planar-straddled conformation corresponds to methyl group rotation by 60°. (c) The planar eclipsed configuration is the transition state, (d) The planar-bisected structure corresponds to conversion without rotation. (From Zebretto et al. [1989].)...

The hfs caused by the protons on the methyl group of the 1-methylcyclopropyl radical would seem to be quite similar to that of the 1-methylvinyl radical (19.48 G) [11a], which was also shown to be a bent c radical. The net difference of between the cyclopropyl ( — 6.7 G) and vinyl radicals (-1-13.4 G) [11a] also indicates that the vinyl radical is more bent than the cyclopropyl radical. The rate constants for the inversion of both cyclopropyl and 1-methylcyclopropyl radicals were also determined [14] by chemical... 

The possibility of cyclization of 3-butenyl radicals is well established, giving apparently only Cy 3, the methylcyclopropyl radicals (9.4 X 10 sec at 40°C) but the opening of the methylcyclopropyl radical is faster (1.3 X 10 sec at 25°C ) so that the cyclization process is essentially reversible K = 1.3 X 10" at 25°C, statistically corrected for A and This is inferred mainly from products which appear to result from 1,2-vinyl migration (Scheme 17) 3.436-448... 

An early example of intramolecular addition of an alkoxyl radical had been reported for a steroid bearing an allylic nitrite ester group the possibility of intramolecular addition of an allyloxyl radical had been put forward to rationalize the formation of an epoxide.But if this is the real pathway, it must be a very special one. Indeed, it is now well known that the behavior of oxyranyl alkyl radicals parallels the behavior of methylcyclopropyl radicals (Section V.2.B) and that the reverse -scission pathway toward allyloxy radicals is very easy and very This is, in fact, faster than the other... 

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). 

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).

Quite interestingly the behavior of the allyl radical and its cyclized counterpart the cyclopropyl radical is completely different from that of the homoallylic-methylcyclopropyl system. It does not seem that cyclized products resulting from the allyl radical have ever been observed. The opening of the cyclopropyl radical is, however, also a very slow process. Nevertheless, opening of substituted cyclopropyl radicals is observed when the substituents highly stabilize the allylic radical. In the same way photolytic cleavage of cyclopropanes is facilitated when each of the radical centers formed is stabilized. ... 

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... 

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