From Cyclopropyl Derivatives

In another instance, Kocovsky et al. have reported a Pd(II)-catalyzed carbonylation of halomercurio alcohols for the synthesis of 8-lactones [112] (Scheme 65). Bromomercurio alcohol 299 derived from cyclopropyl derivative was subjected to a Pd(II)-catalyzed carbonylation in the presence of p-benzoquinone. Whereas the use of stoichiometric amount of palladium catalyst led to lactone 300 in 55 % yield along with the tetrahydrofuran derivative 301 (11 %), the catalytic version gave rise to a mixture of 300 (14 %) and 301 (44 %). 

Adducts derived from cyclopropyl-TMM reactions are versatile synthetic intermediates. Alkylidenecyclopropanes have been proven useful in further Pd-cata-lyzed transformations [4], On the other hand, vinylcyclopropanes can undergo smooth thermal ring-expansion to cyclopentenes. Thus, a total synthesis of 11-hy-droxyjasionone (27) was achieved with the cyclopropyl-TMM cycloaddition as the crucial step, and the thermal rearrangement of the initial adduct (28) as an entry to the bicyclo[6.3.0]undecyl compound (29), a key intermediate in the synthetic sequence (Scheme 2.9) [19]. 

It is also evident from the data of Bly et al. (95), Jacobs and Macomber (91), and Garry and Vessiere (99) that neopentyl-type homoallenic systems do not yield cyclopropyl derivatives upon solvolysis, in contrast to the unsubstituted parent system. If they have no substituents at Cj or C3, neopentyl homoallenic substrates yield rearranged acyclic olefins and rearranged solvent-incorporated products exclusively. If they carry an alkyl substituent at Ci, they give both rearranged and unrearranged acyclic products. If a substituent is present on C3 besides the acyclic derivatives, cyclobutyl products also are formed. 

PTC has been extensively used for making cyclopropyl derivatives. The most common reaction involves generation of dichlorocarbene from chloroform, using NaOH and a quaternary ammonium hydroxide. The carbene subsequently reacts with an alkene in high yield. Hydrolysis of dichlorocarbene, normally rapid in the presence of water, is minimal. An interesting and very efficient example of a Michael addition to produce a cyclopropyl derivative is shown in Scheme 4.26. 

Cyclopropyl sulfones were shown to be obtained either by cyclization of y-p-tosyloxy sulfones 232 with base or by treatment of phenylsulfonylacetonitrile 233a or ethyl phenyl sulfonyl acetate 233b with 1,2-dibromoethane in the presence of benzyltriethyl-ammonium chloride (BTEA) and alkali in good yields. Chang and Pinnick synthesized various cyclopropane derivatives 234 upon initial treatment of carbanions derived from cyclopropyl phenyl sulfone with either alkylating agents or a carbonyl compound and subsequent desulfonylation, as shown below. 

Recently, diazocyclopropane (246) was synthesized from cyclopropyl N-nitroso urea (245) and its reaction with 1 has been studied. The cycloaddition gave a mixture of the unique primary adduct 248 together with the [3]-tri-angulane (247) derived from N2 extrusion (Scheme 40) [62]. 

Some fragmentation reactions from cyclopropyl carbenes and aziridine derivatives are as follows ... 

A general method for the generation of aminyl radicals is by treatment of sulphenamides 340, prepared from secondary amines and A-benzenesulphenylphthalimide, with tributyltin hydride in the presence of AIBN (2,2/-azobisisobutyronitrile). The cyclopropyl derivative... 

Both acridone and dibenzo[6,/]azepine produce unexpected products (Scheme 7.39) when reacted with dimethylvinylidene carbene (7.1.18.A). Acridone reacts initially at the nitrogen atom to produce the 10-(3,3-dimethylallenyl) derivative (13%) and a pyrroloacridone (10%) which, if the structure is correct, could be derived from the allene by sigmatropic shifts [16]. The dibenzoazepine reacts as expected to produce a cyclopropyl derivative but, under the reaction conditions, the adduct rearranges spontaneously to yield a 1,6-methanodibenzo[b,/]cyclo-prop [J]azepine, the structure of which was confirmed by X-ray crystallography [17]. 

A general type of chemical reaction between two compounds, A and B, such that there is a net reduction in bond multiplicity (e.g., addition of a compound across a carbon-carbon double bond such that the product has lost this 77-bond). An example is the hydration of a double bond, such as that observed in the conversion of fumarate to malate by fumarase. Addition reactions can also occur with strained ring structures that, in some respects, resemble double bonds (e.g., cyclopropyl derivatives or certain epoxides). A special case of a hydro-alkenyl addition is the conversion of 2,3-oxidosqualene to dammara-dienol or in the conversion of squalene to lanosterol. Reactions in which new moieties are linked to adjacent atoms (as is the case in the hydration of fumarate) are often referred to as 1,2-addition reactions. If the atoms that contain newly linked moieties are not adjacent (as is often the case with conjugated reactants), then the reaction is often referred to as a l,n-addition reaction in which n is the numbered atom distant from 1 (e.g., 1,4-addition reaction). In general, addition reactions can take place via electrophilic addition, nucleophilic addition, free-radical addition, or via simultaneous or pericycUc addition. 

Figure 8. Rotational profiles for methyl, isopropyl and cyclopropyl derivatives (reproduced from ref 59 with permission of the American Chemical Society).

A variety of three-membered carbocycles including cyclopropylcarbonyl and -sulfonyl derivatives, cyclopropylcarbonitriles and -methanols, nitrocyclopropanes, cyclo-propanols and cyclopropylamines have been prepared via the 1,3-elimination of HX. Some representative cyclopropyl derivatives recently prepared by this method are shown in Scheme 116-18 and in equations 8-26. Conversion of chelated homoserine, 5,to chelated 2-amino-4-bromobutyrate and treatment with aqueous base directly affords chelated 1-aminocyclopropane-l-carboxylate (equation 8)19. The 1,3-elimination in 6 interestingly leads to the preferential formation of the cis isomer, from which 7, a key structural element of synthetic pyrethroid insecticides, is obtained (equation 9)20. A sulfur substituent can serve both as an activating group and as a leaving group in this type of reaction and, thus, 1,3-bis(phenylthio)propane affords cyclopropyl phenyl sulfide upon treatment with butyl-... 

A variety of cyclopropyl derivatives has been prepared utilizing this methodology from malonic ester anion or related stabilized carbanions and Michael acceptors such as 56,57310 and 58311. The reactions are nonstereospecific in general as expected from the mechanism... 

Electron-deficient alkenes, either these with conjugating substituents or of enones, undergo Michael-like additions with regiospecific introductions of the nucleophiles, and this approach has been successful for the formation of cyclopropyl derivatives—notably from some nucleosides. An example involves the addition of the anion of bis(phenylsulfonyl)methane to the phenylselenone 173 which gives the adduct 174 in 35% yield. This reaction presumably occurs by Michael addition to C-2 followed by Sn2 ring-closure reaction at C-3 with displacement of phenylselenic acid. Reductive desulfonylation affords the 2,3,-dideoxy-2,3 -cyclopropayuridine 175.199... 

Liu, T. J., and Schneider, H. J. (2002) Additivity and quantification of dispersive interactions-from cyclopropyl to nitro groups Measurements on porphyrin derivatives, Angew. Chem. Int. Ed. Engl. 41, 1368-1370. 

A remarkable dependence of the reactivity on ring size has been found in the series of methylenecycloalkanes (Fig. 9) [106]. The exceptionally low rate constant for methylenecyclopropane indicates that the low solvolysis rates of cyclopropyl derivatives [154] are not only caused by the unfavorable change of hybridization of one ring carbon in cyclopropane but also by the low stability of the cyclopropyl cation relative to a compound with the same hybridization (methylenecyclopropane). The destabilization of the cyclopropyl cation must actually be greater than indicated by the numbers in Fig. 9 as the transition state of the electrophilic attack may already profit from the stabilizing ring-opening process (cf., Section III.B.2). 

FIGURE 11. He(I) photoelectron spectra of cyclopropyl derivatives of C2V symmetry. The first pair of orbitals in 1,1-dimethylcyclopropane has vertical ionization energies of 9.8 and 10.57 eV, in the cyclopropene the energies are 9.42 and 10.02 eV despite their similar appearance the first band derives in these pairs from orbitals of different type... 

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