Cyclopropanation Experimental Procedures

Experimental Procedure 2.2.2. Cyclopropanation with a Chromium Carbene Complex Diethyl n-a/i5-3-Methoxy-3-phenylcyclopropane-l,2-dicart>oxylate [325]. 

Experimental Procedure 3.2.1. Cyclopropanation with an Iron Carbene Conqjlex 1,1-Diphenylcyclopropane [468]... 

Experimental Procedure 3.2.2. Cyclopropanation with a Titanium Carbene Complex (E)-l-Hexyl-2-(2-phenylethenyl)cyclopropane [33]... 

The reaction of acceptor-substituted carbene complexes with alcohols to yield ethers is a valuable alternative to other etherification reactions [1152,1209-1211], This reaction generally proceeds faster than cyclopropanation [1176], As in other transformations with electrophilic carbene complexes, the reaction conditions are mild and well-suited to base- or acid-sensitive substrates [1212], As an illustrative example, Experimental Procedure 4.2.4 describes the carbene-mediated etherification of a serine derivative. This type of substrate is very difficult to etherify under basic conditions (e.g. NaH, alkyl halide [1213]), because of an intramolecular hydrogen-bond between the nitrogen-bound hydrogen and the hydroxy group. Further, upon treatment with bases serine ethers readily eliminate alkoxide to give acrylates. With the aid of electrophilic carbene complexes, however, acceptable yields of 0-alkylated serine derivatives can be obtained. 

Since the first experiments with chiral copper complexes reported by Nozaki [650] and Aratani [1027] many different catalysts have been examined, both for intermolecular and intramolecular cyclopropanations (for a review, see [1369]). Syntheses of natural products [955,1370] and drugs [1371] using asymmetric cyclopropanation with chiral electrophilic carbene complexes have been reported. A selection of useful catalysts is given in Figure 4.20 (see also Experimental Procedure 4.1.1). 

Experimental Procedure 4.2.8. Enantioselective, Intramolecular Cyclopropanation 6,6-Dimethyl-3-oxabicyclo[3.1.0]hexan-2-one [1390]... 

These reactions rapidly found wide use and success, and many other sulfur ylides have been prepared and exploited [194, 195, 203, 204]. Various experimental procedures are to be found in the detailed monograph by Trost and Melvin [204] for sulfonium salts, ylides, epoxidations and cyclopropanations. 

Thermal decomposition of 2-diazohexafluoropropane, or 2-diazo-3,3,3-trifluoro-propanenitrile in excess benzene (150-200 "C, autoclave) resulted in efficient cyclopropanation of an aromatic C-C double bond. In solution, the 7-trifluoromethylnorcaradiene 9 (-bicyclo[4.1.0]hepta-2,4-diene) so formed is in rapid valence equilibrium with the corresponding cycloheptatriene 10 however, this equilibrium is shifted predominantly or completely to the cycloheptatriene side. As a byproduct in the synthesis, the product of carbene insertion into an aromatic C-H bond is obtained. An experimental procedure for the synthesis of 10b can be found in Houben-Weyl, Vol. 19 b, p 1031. 

Transfer of a formylcarbene unit from an a-diazo aldehyde to an alkene has never become popular. The copper-catalyzed cyclopropanation with diazoacetaldehyde to give 5 occurred in low yield, since ketene formation is competitive (for experimental procedure, see Houben-Weyl Vol.E19b, pi224). It appears that with other catalysts and at a lower temperature the cyclopropanation could be more effective. 

Carbenoid addition of diazocarbonyl compounds to pyrrole, A -alkylpyrroles, indole, N-alkylindoles, imidazole, and benzimidazole does not result in cyclopropanation, but leads to the formal products of carbene insertion into a heterocyclic C-H bond (see Houben-Weyl, Vol.E19b, ppll58 and 1334). However, Af-acylpyrroles, and Af-acylindoles - " have successfully been converted into 2-azabicyclo[3.1.0]hex-3-ene-exo-6-carboxylates and alkyl-1,la,2,6b-tetrahydrocyclopropa[ ]indole-exo-l-carboxylate, respectively (for an experimental procedure, see Houben-Weyl, Vol.E19b, pll60). 

Nucleophilic substitution on the cyclopropane ring takes place during irradiation of a mixture of 7-bromobicyclo[4.1.0]heptane and diphenylarside in liquid ammonia giving (bicyclo[4.1.0] hept-7-yl)diphenylarsane (1) in 90% yield. The reaction involves radical-anion and radical intermediates. The experimental procedure used is identical to that for the corresponding phosphorus analog (section 5.2.1.1.15.). ... 

The following products, in addition to many others, were prepared by this experimental procedure l,l-dibromo-2-isopropenyl-2-methylcyclopropane from 2,3-dimethylbuta-l,3-diene (51%) l,l-dibromo-2-methyl-2-(2-methylpropenyl)cyclopropane from 2,4-dimethylpenta-1,3-diene (37%).18 The formation of the adduct to the less-substituted double bond is suggested in the latter case this result should be verified. 

In order to facilitate the search for the stereoselective synthesis of a cyclopropane derivative with a particular substitution pattern, this section is organized according to the carbene (carbenoid) substituents. The sequence of carbenes therefore parallels that in the Houben-Weyl Volume E 19 b on Carbene (Carbenoidc)/Carbine which deals with all aspects of carbene chemistry including scope and limitations of various [2 + 1] cycloadditions. For many classes of carbenes. and. in particular, for typical experimental procedures, cross references are made to the corresponding pages in that volume. 

Since (Z)- and ( )-stereoisomers of unsaturated oxazolones can be obtained using appropriate isomerization procedures, cis and trans isomers of cyclopropane derivatives can be obtained in a stereoselective manner, although special care must be taken with experimental conditions to obtain the best stereoselectivity. Both racemic cis- and fraui-l-amino-2-phenylcyclopropanecarboxylic acid 641 and 644 have been obtained from the corresponding (Z)- or ( )-4-benzylidene-2-phenyl-5(4//)-oxazolone 621 and 642 using diazomethane. Care was taken to affect the... 

In 2001, a modified procedure for sulfur ylide-catalyzed epoxidation, aziridination and cyclopropanation was introduced by Aggarwal and co-workers that utilized the generation of the diazo compounds in situ from tosyl hydrazone salts at 40 °C in the presence of a phase-transfer catalyst [46, 79]. (For experimental details see Chapter 14.12.1). Using this modified protocol, sulfide 4 was shown to be effective for epoxidation and aziridination (see Sections 10.2.1.4 and 10.3), but was not an effective cyclopropanation catalyst (see Table 10.3). Sulfide 28 was tried instead as it had been shown in achiral studies [96] that six-membered sulfides were more effective than five-membered analogues. This change gave rise to... 

We start with their simplest systems and we first consider the parent hydrocarbons benzene and cyclopropane themselves. This enthalpy of formation difference (5i9(Ph, cypr H) is (29.3 0.9) kJ mol Turning now to the simple alkyl derivatives, and 1 and 11, X = Me in particular, we recall that there are no direct experimental data for the enthalpy of formation of gaseous methylcyclopropane but only for the corresponding liquid. Accepting the archival enthalpy of vaporization value from Kolesov and Kozina " is equivalent to accepting their value for the enthalpy of formation of methylcyclopropane,.namely 24.3 kJ mo We so deduce a value for (5i9(Ph, Cypr Me) of [26.1 ( >0.9)] kJ mol some 3 kJ moT different fom that for the parent hydrocarbons. We are not particularly bothered by this 3 kJ moT discrepancy—we recall in footnote 23 a 6 kJmoT spread of values suggested for the enthalpy of vaporization of methylcyclopropane. It is conceptually simplest, and procedurally most precise, to use the identical approach to compare ethylbenzene and ethylcyclopropane, for there are no enthalpy of vaporization measurements for the latter 3MR species. Encouragingly, consistency of results is obtained —the value of i9(Ph, Cypr Et) equal to 26.5 kJmoT is nearly identical to that of i9(Ph, Cypr Me). 

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