Mono-substituted cyclopropanes

In the C NMR spectrum two signals with unusually small shift values [(07/2)2 5c = 7.7 CH 5c = 10.6] and remarkably large CH coupling constants Jch= 161.9 and 160.1 Hz) indicate a mono-substituted cyclopropane ring A. The protons which belong to this structural unit at = 0.41 (AA ), 0.82 BB ) and 1.60 (M) with typical values for cis couplings 8.1 Hz) and trans couplings 4.9 Hz) of the cyclopropane protons can be identified from the CH COSY plot. 

TABLE 16. Energy differences AE (kcal mol ) between the different rotamers of mono-substituted cyclopropanes calculated at the Hartree -Fock level with various basis sets... 

Indeed, in a study of reaction rate and efficiency as a function of geminal substitution of the VCP, it was found that heteroatom substitution was not required to activate the VCP for intermolecular [5+2] cydoaddition (Tab. 13.14) [51]. Substitution for -H at the 1-position of the cyclopropane with -Me, -TMS, or - Pr led to an acceleration of the reaction that correlated with size of the substituent. Significantly, good to excellent yields and high, if not complete, regioselectivities are observed with a variety of mono-substituted alkynes and simple, unactivated VCPs. 

The reaction is carried out at ambient temperature and nearly complete enantioselectivity (>99%) is observed for mono- and 1,1-disubstituted olefins with diazoacetates. With all copper catalysts, the transkis selectivities in the cyclopropanation of mono-substituted olefins are only moderate. The transkis ratio depends, in this case, mainly on the structure of the diazo ester rather than the chiral ligand (eq 2). It increases with the steric bulk of the ester group of the diazo compound. With the BHT ester, the more stable trans isomer is formed with selectivities up to >10 1. The steric hindrance usually prevents ester hydrolysis, but the BHT group can be removed by reduction with LiAlHj. The trans isomer is even enriched by the reduction procedure because the cis isomer reacts more slowly. 

The anodic oxidation of polyalkyl substituted cyclopropanes and spiro[2.n]alkanes gave mono- and dimethoxy products which resulted from the cleavage of the most highly substituted C-C bond, in contrast to the results obtained by acid-catalyzed methanolysis of alkyl-substituted cyclopropane by the same authors. Those results suggest that a direct (7-electron transfer from the most strained a bond of cyclopropane to the anode may be the initiation step. 

Since mono-adducts obtained from reacting 11-substituted bridge[10]annulenes with triazolinediones contain a substituted cyclopropane ring, we attempted nucleophilic displacement under stringent reaction conditions. Even with naked fluoride ion the substrates were recovered unchanged... 

The synthesis of tricarbonylchromium(O) complexes of mono-, di- and tri-substituted cyclopropanes, e.g. 150, has been accomplished through the reaction of tricarbonyl(styrene) chromium(O) complexes 151 with phosphorus and sulfur ylides. ... 

PtCla(C2H4)]2 reacts with various mono-, di-, and tri-alkyl substituted cyclopropanes via insertion into the least substituted carbon-carbon bond to yield platinacyclobutanes such as (13). At low temperature, reaction with pyridine yields the bis-pyridine adduct, but on warming, the j -compIex (14) is formed. Arylcyclopropanes react with [PtCla(CaH4)]a in a similar fashion, and a kinetic study indicates an initial cyclopropane-Pt co-ordination. " Reaction of (diphos)PdCl2 with 1,4-dilithiobutane yields the palladocyclopentane (diphos)-... 

Reactions between em-dihalogenocyclopropanes and lithium dialkylcuprates can be controlled in such a manner as to produce intermediate copper-bonded mono-alkylcyclopropanes (22), which can be alkylated with a second, different alkyl halide, leading to unsymmetrically alkyl-substituted cyclopropanes. The potential for this interesting one-pot dialkylation sequence is illustrated by convenient syntheses of the sesquiterpenes sirenin (23a) and sesquicarene (23b), starting with the dichloro-cyclopropane (21) (Scheme 10). ... 

Nenajdenko et al. described the first example of addition of a 1,2-dication to C-C mutiple bonds. The only S-S dication found to participate in this reaction was the highly strained dication 115 derived from 1,4-dithiane. The reaction with alkenes 119 proceeded under mild conditions and led to derivatives of dithioniabicyclo[2.2.2]octane 120 as shown in Equation (33) and Table 21 <1998JOC2168>. This reaction was sensitive to steric factors and proceeded only with mono and 1,2-disubstituted ethylenes. Only alkenes conjugated with aromatic or cyclopropane moieties underwent this reaction. For the 1,2-disubstituted alkenes used in this study, the relative configuration of substitutents at the double bond was preserved and only one diastereomer was formed (see entries 2 and 3). 

Reaction with alkenes is sensitive to steric factors - in the case of dication 49, only reaction with mono- and 1,2-disubstituted ethylenes afforded identifiable reaction products. Only alkenes conjugated with aromatic or cyclopropane moiety undergo this reaction. In the case of 1,2-disubstituted alkenes, the relative configuration of substitutents at the double bond is preserved and only one diastereomer is formed. 

Aryl- and alkenyl-substituted oxiranes, when submitted to treatment with super-basic reagents, undergo a highly regio- and stereo-selective 3-exo-cyclization leading to cyclopropylmethanol derivatives (Scheme 46). The process has be applied to mono- and di-hydroxy-substituted substrates, thus leading to polyhydroxylated cyclopropanes.78... 

Problems with subsequent reaction of a 1-halocyclopropene may be avoided by reduction of the dihalocyclopropane to a monohalocyclopropane prior to dehydrohalogenation. Thus 3,3-dimethylcyclopropene may be obtained in multi-gram quantities by treatment of l-bromo-3,3-dimethylcyclopropane with potassium t-butoxide in DMSO at —78 °C19). Dehydrohalogenation of a series of related 3,3-dialkyl substituted monochloro- or monobromo-cyclopropanes leads to moderate yields of cyclopropenes (11, R = alkyl, alkenyl, aryl, CN, Cl, Rl = H, Ph, t-Bu, R2 = H)20) Indeed, dehydrobromination of (12) leads to either mono- or di-cyclopropenes 2l>. Reaction of a dihalocyclopropane with an alkyl lithium at low temperature followed by carboxylation of the derived 1-lithio-l-halocyclopropane provides a convenient source of 1-halocyclopropane carboxylates dehydrohalogenation leads to cyclo-... 

These cyclopropane vs olefin enthalpy of formation differences do not increase monotonically with the number of substituents. Worse yet, differences are found to be of differing signs. That is, there is no obvious pattern for all of the enthalpies of the cyclopropanation reaction 3. Neglecting any enthalpic contribution from the CH2 or cyclopropanation reagent and considering only un-, mono- and di-substituted olefins and cyclopropanes, we find the enthalpy of reaction 3 is rather coarsely equal to (3 2) kJ moT per alkyl substituent We will now accept this 3 kJ moF per alkyl substituent for reaction 3, where we admit the absence of justification and motivation other than arithmetic and convenience. We are forced to tolerate discrepancies of a few kJmoT per substituent differences between our correlations/models and experiment of several kJmoT must be considered as acceptable for our analysis. ... 

Nearly all common mono- and disubstituted acetic acids, including several functionally substituted examples, have been reported to metalate. Unsaturated as well as saturated alicyclic carboxylic acids form dianions, but cyclopropane carboxylic acid is exceptional. Low yields of alkylated products are produced,14,20 suggesting incomplete dianion formation. 

Cyclopropanes substituted with four or less functional groups were synthesized in reasonable yield using -vinylsulfoximine derivatives and mono- or di-activated (Table 27) or even nonac-tivated (Table 28) carbon nucleophiles. 

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