Cyclopropyl transfer

Falck and co-workers [154] have studied reactions of alkoxyalkyltributyltins with acid chlorides, and in one case studied the stereochemistry of the reaction, which proceeded with 98% retention. Cyclopropyl transfer via reaction with a nucleoside bromide has also been carried out [155], The traditional catalysts [Pd(PPh3)4 or PdCl2(PPh3)2] were used, but with various additives (LiCl, CuCN). 

The scope and limitations for transfer hydrogenation employing either the iron porphyrin system or the combination of iron compound/terpy/PPhs are listed in Table 8. In most cases, the FeCVterpy/PPhs system displays a higher activity. Except for chloromethyl- and cyclopropyl-acetophenone, the desired products were obtained in good to excellent yields. It should be noted that a ring opened product was not observed when cyclopropyl acetophenone was employed. Hence, a radical-type reduction pathway was excluded and a hydride mechanism appeared to be reasonable. 

The Norrish-Yang reaction [20] is based on the photochemical excitation of ketones followed by an intramolecular hydrogen transfer with the formation of biradicals. Wessig and coworkers used this procedure to prepare functionalized cyclopropyl ketones as 5-75 from 5-72 (Scheme 5.15) [21]. The substrate employed con-... 

Cu(II) EPR signal in nitriles as solvent as well as by polarographic measurements 144>. Similarly, the EPR signal disappeared when Cu(OTf)2 was used for catalytic cyclo-propanation of olefins with diazoesters 64). In these cases, no evidence for radical-chain reactions has been reported, however. The Cu(acac)2- or Cu(hfacac)2-eatalyzed decomposition of N2CHCOOEt, N2C(COOEt)2, MeCOC(N2)COOEt and N2CHCOCOOEt in the presence of cyclopropyl-substituted ethylenes did not furnish any products derived from a cyclopropylcarbinyl - butenyl rearrangement128. These results rule out the possible participation of electron-transfer processes and radical intermediates which would arise from interaction between the olefin and a radical species derived from the diazocarbonyl compound. 

A different result was obtained in the cycloaddition to methylenecyclo-propanes 216-218 tearing alkoxycarbonyl substituents on the cyclopropyl ring. In this instance, 1,2,3-triazoles 220 isomeric with the triazolines 219 were formed in the reaction [57]. The formation of triazoles 220 is rationalised by the intermediate formation of triazolines 219, which are unstable under the reaction conditions and undergo a rearrangement to the aromatic triazoles via a hydrogen transfer that probably occurs with the assistance of the proximal ester carbonyl (Scheme 35). The formation of triazoles 220 also confirms the regio-chemistry of the cycloaddition for the methylene unsubstituted methylene-cyclopropanes, still leaving some doubt for the substituted ones 156 and 157. 

Finally, there has also been research into the ozonolysis of allenes. Thus sterically hindered allenes react by transfer of one oxygen atom, forming a mixture of reaction products214. Recently, the ozonolysis of a cyclopropylallene has been shown to yield a diastereomeric mixture of cyclopropyl esters215. 

In the case of cyclopropyl-diazo-acetate 72 energy transfer reduces the extent of intramolecular in favour of the intermolecular reactions 146). 

The observed acid-catalysed conversion of complestatin (289) into chloropeptin L (291) has been envisioned" " as proceeding through a cyclopropyl intermediate (290) (see Scheme 94). An intramolecular oxygen-transfer reaction illustrated in Scheme 95 has been proposed" to explain hydroxylation of the aromatic nucleus, viz. formation of (292), during the course of a modified Polonovski reaction on galanthamine. 

Triethylamine as the electron donor was also used by Mattay and co-workers in tandem fragmentation cyclization reactions of a-cyclopropylketones. The initial electron transfer on the ketone moiety is followed by the fast cyclopropyl-carbinyl-homoallyl rearrangement, yielding a distonic radical anion. With an appropriate unsaturated side chain within the molecule both annealated and spi-rocyclic ring systems are accessable in moderate yields (Scheme 41) [62]. 

Cyclopropyl carbanions are capable of maintaining their configuration whereas the CT-radical has been shown to reach inversion equlibrium with a rate constant of lO" s". ITie cyclopropyl bromide 13, and the corresponding iodide, are reduced in a single two-electron polarographic wave and the S +)-isomer yields the R(-)-hydrocarbon with 26% enantiomeric excess [67, 68]. Such a substantial retention of configuration during reduction of the carbon-bromine bond indicates a very fast second electron transfer process. Results from reduction of the cyclopropyl bro-... 

A recent report has shown that tricyclopropylbismuth can be utilized in the cross-coupling reaction with aryl halides and triflates [57]. Representative examples are shown in Scheme 38. Addition of a base activator and excess of the bismuth reagents are necessary to obtain the coupling products in good yields, although more than one cyclopropyl group was transferred when 0.5 equivalents of... 

Inhibition mechanisms by A/-cyclopropyl MPTP analogues are also discussed in terms of two catalytic pathways, one of which is based on an initial SET step from the nitrogen lone pair, as proposed by Silverman, and the second is based on an initial a-carbon hydrogen atom transfer (HAT) step, as proposed by Edmondson, leading to a radical and dihydropyridinium product formation. The observation that MAO B catalyzes the efficient oxidation of certain 1-cyclopropyl-4-substituted-1,2,3,6-tetrahydropyridines to the corresponding dihydropyridinium metabolites suggests that the catalytic pathway for these cyclic tertiary allylamines may not proceed via the putative SET-generated aminyl radical cations [122], Further studies will be necessary to clarify all the facets of the mechanism of inhibition of MAO by cyclopropylamines. 

Direct evidence for triplet-triplet transfer has been provided by sensitizing both the isomerization of cis- or ira/w-olefins,28 38 79,80 and the dimerization of some cyclic olefins81-83 with carbonyl compounds. Furthermore, the phosphorescence of some carbonyl compounds can be quenched by olefins (for example, acetone with 2-pentene30 and phenyl-cyclopropyl ketone with 2-methyl-2-butene37). On the other hand, the phosphorescence of benzophenone is not quenched by 2-methyl-2-butene37 nor is the photoreduction of benzophenone quenched efficiently by cyclohexene (Table II). 

The former reduction is thought to occur by two single electron transfers (SET) from the metal surface to the cyclopropane derivative providing a halide and cyclopropyl anion initially. The latter is protonated by the solvent thus leading to the monohalogen derivative which can undergo the reduction process for a second time. 

The gas-phase heats of formation obtained from pulsed ion cyclotron resonance (ICR) spectroscopy showed that the tertiary 1-cyclopropyl-1-methylethyl cation (20) is more stable than the 1-phenyl-1-methylethyl cation by 0.8 kcalmol 1, while the secondary 1-cyclo-propylethyl cation (18) is less stable than the 1 -phenylethyl cation by 4.8 kcal moT125. Thus a substantial reversal of the stabilization of the phenyl over cyclopropyl groups is observed. The results were also rationalized by STO-3G calculations for the isodesmic reaction involving proton transfer (equation 71). 

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