Cyclopropane analog

Racemic -amino acids, namely 3,3-ethano- -alanine (193 a) and its spiro-cyclopropanated analog 193b, have been prepared by simple one-step hydrogenolytic reduction and deprotection of the primary Michael adducts 94 b and 94 d (Scheme 57) [9,21b]. As methyl esters cannot be deprotected under these conditions, only reductive dechlorination and debenzylation was observed for compounds 91t,u (Scheme 57) [7k]. This looks promising for the construction of... 

The vinylcyclopropane 10 is a useful chiral building block for organic synthesis, as the vinyl group can be oxidatively cleaved if desired and further functionahzed (Scheme 14.1). Either diastereomer 20 or 21 of the cyclopropane analog of phenylalanine can be readily prepared from 10 [40]. Corey has reported another elegant appHcation of the vinylcyclopropane 10 in the asymmetric synthesis of the antidepressant (-i-)-sertraline 22 [52]. 

Another application of this chemistry is the asymmetric synthesis of the cyclopropane analog 25 of the breast cancer treatment agent tamoxifen 26 (Scheme 14.2) [53]. The Rh2(S-DOSP)4-catalyzed reaction of phenyldiazoacetate 3 with diarylethylene 23 at... 

Various substituted cyclopropanes have been shown to undergo nucleophilic addition of alcoholic solvents. For example, the electron transfer reaction of phenylcyclopropane (43, R = H) with p-dicyanobenzene resulted in a ring-opened ether 44. This reaction also produced an aromatic substitution product (45, R = H) formed by coupling with the sensitizer anion. This reaction is the cyclopropane analog of the photo-NOCAS reaction, but preceded it by almost a decade. 

We close this section relating double bonds and cyclopropanes with dicarbon and its formal cyclopropanated analogs cyclopropyne (44), A 3-bicyclo[1.1.0]butene (45) and [1.1. ljpropellane (46). That is, we consider the series of compounds C2, C2(CH2), C2(CH2)2 and C3(CH2)j. Admittedly, C2 is not a hydrocarbon and somehow does not really belong in the current series, but analysis making use of its inclusion in its reasoning is conceptually no worse than... 

Cycloalkanes and Saturated Hetero-cyclics The chemical shifts of the CH2 groups in monocyclic alkanes are given in Table 4.7. The striking feature here is the strong shift to the right of cyclopropane, analogous to the shift of its proton absorptions. 

From the inorganic compendium we find an enthalpy of formation of C2 of 831.9 kJ mol. Cyclopropyne remains but a chemist s chimera, but only a short time ago, so were A -bicyclo[1.1.0]butene and [l.l.ljpropellane. From the classical (albeit gas-phase) combustion calorimetric measurement of the enthalpy of formation of bicyclobutane and modem gas-phase ion measurements, the gas-phase enthalpy of formation of A -bicyclo-[l.l.OJbutene has been determined to be (544 42) kJ mol". From reaction calorimetry and some judicious estimates, the enthalpy of formation of gaseous [l.l.ljpropellane has been measured and then chronicled among other, mostly normal 3MR species, as (351 4) kJ mol". Yet, before we get too complacent, it is clear that anything even approximating a constant cyclopropanation energy is not found in the series of current interest dicarbon and its formal cyclopropanated analogs 44-46. 

Liu et al. reported in 2003 on the synthesis and cytotoxicities of 3 -cyclopropane analogs with both Tot- and 7(3-OH and 2 R)- and 2 (5)-OH functionalities. Both 2 - R) isomers were 400 times less active than paclitaxel in A2780 cancer cell assays, and 2 -(5) isomers displayed even weaker cytotoxicities. Unsatisfactory results may have developed from small volumes of the 3 -cycloprapane, which is similar to 3 -methyl in 9(R)-dihydro paclitaxels as reported earlier. As mentioned, larger groups such as isobutyl or isobutenyl may interact with the receptor better. 

Cyclopropane analog " 98 showed microtubule disassembly inhibitory activity comparable with paclitaxel, but lower than docetaxel. The author thus demonstrated that the oxetane ring is not essential for the interaction of paclitaxel analogs with microtubules when the C-ring conformation is locked by cyclopropane, but the oxygen atom in the D ring of paclitaxel may participate in the stabilization of a dmg-tubulin complex. 

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... 

Cyclobutyl compounds were found S7) to have reactivities closely related to the ones already disclosed for open chain and other cyclic derivatives 7 8,U). Moreover, in several instances, compounds possessing a cyclobutane ring have been prepared from a-selenoalkyllithiums and cyclobutanones (Compare Scheme 8B to 8 A) using the strategy already presented. This is not, however, the case of cyclopropane analogs due to the unavailability of cyclopropanones. 

The following factors, however, make a clean realization of such a reaction more difficult than in the corresponding cyclopropane analog for the following reasons ... 

The striking feature here is the strong shift to the right of cyclopropane, analogous to the shift of its proton absorptions. 

The 2n aromatic system and the saturated cyclopropane analogs are discussed separately. 

In a more recent and improved approach to cycloproparadicicol (synthetic cyclopropane analog of radicicol) the synthesis was achieved via a stable cobalt complex, which led to the cyclized products as a 2 1 mixture of isomers in 57% yield (Scheme 5.3). The complexation of the ethynyl group with Co2(CO)8 avoids a competitive ene-yne metathesis and brings into proximity the double bonds favoring RCM. 

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