Cyclopropanes computational model

Based on the experimental results of azetidine, thia- and cyclopropane analogs of D-ring in paclitaxel, as well as a computational prediction of a taxol minireceptor model, some taxoids devoid of the D-oxetane ring, including D-seco analogs, were proposed to bind to tubulin in similar free energies to that of paclitaxel, which... 

Aqueous phase acidity for a number of hydrocarbons has been computed theoretically. A continuum dielectric solvation model was used and B3LYP/6-311-I— -G((i, p) and MP2/G2 computations were employed. Some of the results are given in Table 6.5 There is good agreement with experimental estimates for most of the compounds, although cyclopropane is somewhat less acidic than anticipated. 

Substrate probes have aided mechanistic understanding of the key C— H activation step in the MMOH reaction cycle. Chiral alkanes and radical-clock substrate probes " " were used to discriminate between radical recoil/rebound and nonsynchronous concerted insertion pathways. A short lifetime (< 150 fs) estimated for the putative radical species derived from cyclopropane-based radical-clock substrates favors the latter process,whereas partial racemization of chiral ethane substrate is consistent with the former scenario. A unifying model was proposed, in which both recoil/rebound and concerted reaction channels are available for a bound radical intermediate and the partitioning between each trajectory is dependent on the substrate. Formation of carboca-tion-derived products from certain probes implicates yet another route involving a formal OH+ insertion.Participation of multiple species capable of oxygen transfer is an emerging mechanistic view in both heme and nonheme systems, as exemplified by the studies of cP450s and their synthetic models.Scheme 3 depicts various density functional theory (DFT) models of MMOHq and their computed reaction pathways, which are reviewed in detail elsewhere. 

Synthesis of Cyclopropane (191. The two isomeric cyclopropanes (19) and (20) were examined against the computer graphic model and the trans isomer (19) was predicted to be an active compound. The model also predicted that the cis isomer (20) would be considerably less active. The cyclopropanes were made as shown in Figure 7. Copper (11) catalysed addition of ethyl diazoacetate to the styrene (17)... 

Synthesis of Cvclobutane (271. The computer graphic model indicated that the trans isomer of this compound would be considerably more active than the cis isomer. Thus the cyclobutane ester (24) [made by Perkin ring synthesis (10-111 followed by Krapcho decarboxylation (12)] was equilibrated to the trans isomer before hydrolysis to the acid (25). This was converted into the amide (26) and reduced to the cyclobutane amine (27) by standard methods (Figure 9). This cyclobutane (27) proved to be an active compound, though slightly less active than the closely related cyclopropane (19). 

The reactivity of carbenes/carbenoids towards C=C bonds continues to attract much attention from theoretical and synthetic chemists alike. Calculations using different levels of theory have thus been conducted to better understand the reactivity of cyclo-propenylidene towards C=C bonds. This DFT study has suggested that the reaction involves two pathways from a common intermediate to give products featuring three-and four-membered rings, respectively. Computational methods applied for the first time to intra- and inter-molecular cyclopropanations involving oxiranyllithiums have provided mechanistic rationale for such carbenoid reactions. " While the intramolecular cyclopropanation of oxiranyllithiums equipped with an olefinic moiety (i.e., 1,2-epoxyhexene used as model substrate) proved to follow either a two-step carbolithiation pathway or a concerted methylene transfer, the latter route predominates for intermolecular cyclopropanation. 

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