Cyclopropyl derivative

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. 

Fig. 6 Metabolic pathway of synthetic pyrethroids in soil (S) and plants (P). R, aryl or cyclopropyl derivative R, alkyl or isobutenyl group...

Other factors which affect the case of electrocyclic ring opening include the nature of substituents which can stabilize or destabilize the development of possible charge and the release of strain in small cyclic systems. Thus different stereochemistries have been observed in the ring opening of cyclopropyl derivatives. All cis derivatives generate an all-cis allyl cation but the anti derivatives will form the all trans cation. 

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... 

Dibromoethane normally reacts with activated methylene groups to produce cyclopropyl derivatives [e.g. 25, 27], but not with 1,3-diphenylpropanone. Unlike the corresponding reaction of 1,3-dibromopropane with the ketone to form 2,6-diphenylcyclohexanone, 1,2-dibromoethane produces 2-benzylidene-3-phenyl-tetrahydrofuran and the isomeric 2-benzyl-3-phenyl-4,5-dihydrofuran via initial C-alkylation followed by ring closure onto the carbonyl oxygen atom (Scheme 6.2) [28],... 

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. 

Another A/-substituted cyclopropylamine, 2-(4-imidazolyl)cyclopropylamine (44), is also a potent inhibitor of rat brain MAO in vitro [113], and A/-cyclopropyl derivatives of tryptamine (45-47) were reported to be inhibitors for mitochondrial and bovine plasma MAOs [114],... 

Double deprotonation/alkylation of (/ )-4-phenyl-3-oxazolidineacetonitrile with LDA/HMPA and epibromohydrin or triflylmethyloxirane afforded the cyclopropyl derivative with a diastereomeric ratio of 44 37 12 7, which was independent of the reaction conditions and the nature of the electrophile70. Since separation of the main isomers by flash chromatography (silica gel, ethyl acetate/hexane 40 60) was possible, optically pure 1 -aminocyclopropanecarb-oxylic acids (methanohomoserines) were obtained after further transformations. 

The mechanism of this unusual cis addition has not been clarified. The bromoethyl derivative 2 can be further alkylated (intramolecularly) to give the deuterated cyclopropyl derivative 3. Once again, cis addition predominates, with 46% de. Upon hydrolysis of the cyclopropyl derivative, optically active (V)-l-amino-cyclopropane-2-r/2-l-carboxylic acid (4) in 44% yield and 46% ee is obtained. 

Chalcone analogs of pyridine ketones (33) and the corresponding cyclopropyl derivatives 34, which are molecules of biological interest, have been studied (74BSF1427 74BSF1442) by NMR, IR, and UV spectroscopy in their isomeric forms. The N,0-trans conformation prevails in the 2- and 3-substituted pyridines and, in derivative 34, coplanarity of the pyridine ring and carbonyl plane is reported (74BSF1442). 

As shown in equation 55, when the benzyl ether of ci.s-2-butcn-1,4-diol is treated with bis(iodozincio)iodomethane, the cyclopropylzinc intermediate is obtained and reacts with various electrophiles. The obtained cyclopropyl derivative has all-d.v configuration. In this reaction, zinc halide, which is present in the solution, plays an important role79. 

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

FIGURE 1. Conformations of cyclopropyl derivatives, characterized by dihedral angle t(M—Cl—C4—X) perspective views (above) and Newman projections down theC4—Cl bond (below). M is the midpoint of the C2—C3 bond... 

Reductive 1,3-elimination reaction of alkyl dihalides constitutes one of the classical methods for the preparation of cyclopropyl derivatives and is particularly useful for the synthesis of highly strained polycyclic hydrocarbons. A new preparation method of [l.l.ljpropellane, more versatile than the original Wiberg s method, has been devised3,4. Thus, treatment of l,l-dibromo-2,2-bis(chloromethyl)cyclopropane with alkyllithium or lithium powder affords [1.1. ljpropellane by two successive 1,3-eliminations of halogens by way of 1 -bromo-2-(chloromethyl)bicyclo[l. 1. Ojbutane (equation 1). This method has been... 

Active methylene and methine compounds bearing a leaving group (X) on the y-carbon atom can afford cyclopropyl derivatives via 1,3-elimination of HX. 1,2-Elimination to give alkenes and direct nucleophilic substitution by base may compete with the 1,3-elimination, particularly in the preparation of excessively strained cyclopropyl derivatives. The preferred reaction course is, however, highly dependent on reaction conditions, especially on the nature of the base and solvent employed, as exemplified by the reactions of 4 (equation 7) 4. 

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-... 

Nucleophilic attack on a rt-allyl ligand of a metal complex occurs in general at one of the terminal carbons to afford allylated products. The attack, however, may be directed to the central carbon atom of the 7i-allyl group to produce cyclopropyl derivatives by appropriate choice of nucleophile, metal ligand and reaction conditions (equation 33). A variety of nucleophiles (pA"a > 20) including ester and ketone enolates and a-sulfonyl carbanions react with... 

Functionalized cyclopropyl derivatives can be prepared via Michael addition of carbon nucleophiles carrying a leaving group at the a-carbon followed by intramolecular substitution as depicted in equation 125. Anion-stabilizing a-substituents in the nucleophiles... 

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... 

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