Distal cleavage

Riegert U, G Heiss, P Fischer, A Stolz (1998) Distal cleavage of 3-chlorocatechol by an extradiol dioxygenase to 3-chloro-2-hydroxymuconic semialdehyde. J Bacterial 180 2849-2853. 

As illustrated for monosubstituted methylenecyclopropanes 5 and 6, a scrambling of the substituent R can be envisioned to result from several processes at different stages of the reaction, e.g. involving equilibration of TMM or allyl complexes. This would lead to more or less efficient scrambling of substituents with respect to the original substrate, depending on the relative rates of equilibration and cycloaddition. Clearly, equilibration reactions of this type require TMM-type intermediates and thus distal cleavage of the methyienecyclopropane. 

Interestingly, bicyclopropylidene (7) also reacts with selected electron-deficient open-chain al-kenes, e.g. diethyl fumarate. When tris(2-phenylphenyl) phosphite is employed to modify the nickel catalyst, the yield of the [2 + 2] cycloadduct 10 amounts to 34% and the [3 + 2] cycloadduct 11 is formed as a minor product. Additionally, two diastereomers of the double [3 + 2] cyclo-adduct 12, formally arising from 7 by proximal cleavage of one cyclopropane ring and distal cleavage of the other, are formed in 15.6% yield. ... 

It must be emphasized that in the case of these unsaturated diesters distal cleavage leading to Q-symmetrical products occurs exclusively. Additionally, conservation of the reactant stereochemistry is not achieved with dialkyl maleates significant or even major amounts of transS are formed. 

Whereas palladium(0)-catalyzed reactions of dialkyl fumarate and dialkyl maleate yield reaction products identical to those obtained from the phosphane-modified nickel-catalyzed reactions (vide supra), analogous palladium(0)-catalyzed reactions with ( )-but-2-enoic or (E)-cinnamic acid derivatives lead to different products to the nickel-catalyzed reactions, i.e. in the palladium-catalyzed reactions formal distal cleavage of but-2-enoic MCP occurs to provide methyl tra i-2-methyl-4-methylenecyclopentanecarboxylate (12, R = Me) and methyl trans-4-methylene-2-phenylcyclopentanecarboxylate (12, R = Ph), respectively." Yields and stereoselectivities are slightly higher with palladium(O) catalysts. When R = Me, 7.4% of the C-C double bond isomerization product, methyl traM -2,4-dimethylcyclopent-3-enecarboxylate (13, R = Me), is additionally obtained, raising the combined yield of cyclocodimers to 49.9%. With methyl (jE )-cinnamate, analogous isomerization only occurs upon workup, i.e. distillation of the crude product. 

Methylenecyclopropanes 9 with geminally disubstituted alkene moieties undergo palladium-catalyzed [3-1-2] cycloaddition reactions with carbon dioxide under pressure. Besides cycloadduct 10 arising from formal distal cleavage of the MCP, furan-2(5//)-one 11, resulting from double-bond isomerization, is formed in variable amounts, depending on the substrate as well as the specific catalyst used. ... 

The pattern and efficiencies of strand cleavage at GG steps in duplex DNA reflect the ability of a radical cation to migrate from its initial position through a sequence of base pairs. In an illustrative example, we consider the photochemistry of AQ-DNA(l), which is shown in Fig. 4. AQ-DNA(l) is a 20-mer that contains an AQ group linked to the 5 -end of one strand and has two GG steps in the complementary strand. The proximal GG step is eight base pairs, ca. 27 A, from the 5 -end linked to the AQ, and the distal GG step is 13 base pairs (ca. 44 A) away. The complementary strand is labeled with 32P at its 5 -terminus (indicated by a in Fig. 4). 

The cleavage of the 0-0 bond of the hydroperoxide is promoted by the push-pull mechanism shown in Fig. 4, in which the native HRP reacts with the unionized form of the hydroperoxide. Thus, the latter is converted into a much better nucleophile upon transfer of its proton to the distal basic group (His 42). 

In the extensively studied monoheme yeast CCP (YCCP) and HRPC, the distal cavity of the peroxidatic heme contains conserved arginine and histidine residues, positioned to maximize the rate of heterolytic oxygen cleavage in compound I formation. In both YCCP and HRPC,... 

---