Pyrazolines cyclopropane formation

The addition of diazomethane to a,/l-unsaturated ketones, e.g., benzalace-tone and benzalacetophenone, results in A -pyrazolines (16) which decompose thermally to the conjugated ketones (17). Cyclopropane formation is not observed in this instance. 

Diazomethane is also decomposed by N O)40 -43 and Pd(0) complexes43 . Electron-poor alkenes such as methyl acrylate are cyclopropanated efficiently with Ni(0) catalysts, whereas with Pd(0) yields were much lower (Scheme 1)43). Cyclopropanes derived from styrene, cyclohexene or 1-hexene were formed only in trace yields. In the uncatalyzed reaction between diazomethane and methyl acrylate, methyl 2-pyrazoline-3-carboxylate and methyl crotonate are formed competitively, but the yield of the latter can be largely reduced by adding an appropriate amount of catalyst. It has been verified that cyclopropane formation does not result from metal-catalyzed ring contraction of the 2-pyrazoline, Instead, a nickel(0)-carbene complex is assumed to be involved in the direct cyclopropanation of the olefin. The preference of such an intermediate for an electron-poor alkene is in agreement with the view that nickel carbenoids are nucleophilic 44). 

Copper salts accelerate the decomposition and completely reverse the product distribution in favour of the cyclopropane derivatives. The solvent also seems to be of great importance in determining the product distribution. The ratio olefin-cyclopropane is increased by using solvents with higher dielectric constants". This phenomenon is illustrated by the decomposition of 4-(l-bromo-l-methylethyl)pyrazolines (87) ". In non-polar solvents both a cyclopropane (88) and an olefinic product (89) are formed (equation 18). In polar solvents, both protic and aprotic, the cyclopropane 88 is the only product observed. The rate of formation of 88 is very solvent dependent. A striking feature is a very strong acceleration rate in the cyclopropane formation with increasing solvent... 

The electron deficiency in the ketocarbene intermediate can be satisfied through various types of addition reactions. Cyclopropane derivatives are the result of inter- or intra-molecular cycloaddition to al-kenic double bonds. In the case of Z-group-activated C=C, the initial reaction of the diazo ketone is usually a 1,3-dipolar cycloaddition to give a pyrazoline derivative (see equation 9) on heating these decompose with nitrogen elimination, resulting in cyclopropane formation (e.g. 29 30 31). The... 

The addition of diazomethane to methyl a-acetamidoacrylate (99) followed by pyrolysis is the basis of a newly reported preparation of 1-aminocyclo-propanecarboxylic acid derivatives. Diazomethane adds to olefins (1(X)) and, when X or Y = acetyl, thermal isomerization to A -acetyl-A -pyrazolines occurs as well as other side-reactions and cyclopropane formation. Neither from these, nor by thermolysis of 3-acyl-3-alkoxycarbonyl-A -pyrazolines, were the yields of cyclopropanes good. From thermolysis of 4-vinyT3,3-di-(alkoxycarbonyl)pyrazolines, cyclopropanes were undetected. 

Pyrolysis at 190° of the resulting diastereomeric A -pyrazolines (8) and (11) leads to elimination of nitrogen and formation of the cis- and tmns-cydo-propanecarboxylates (9) and (12), respectively. Thermal decomposition of the A -pyrazoline (13) affords methyl tiglate (14) in addition to the cyclopropane derivative (15) in a ratio 2 1, while A -pyrazolines such as (3) give only 0L,[i- or, y-unsaturated esters, and no cyclopropane derivatives. 

As it is known from experience that the metal carbenes operating in most catalyzed reactions of diazo compounds are electrophilic species, it comes as no surprise that only a few examples of efficient catalyzed cyclopropanation of electron-poor alkeiies exist. One of those examples is the copper-catalyzed cyclopropanation of methyl vinyl ketone with ethyl diazoacetate 140), contrasting with the 2-pyrazoline formation in the purely thermal reaction (for failures to obtain cyclopropanes by copper-catalyzed decomposition of diazoesters, see Table VIII in Ref. 6). 

Based on a detailed investigation, it was concluded that the exceptional ability of the molybdenum compounds to promote cyclopropanation of electron-poor alkenes is not caused by intermediate nucleophilic metal carbenes, as one might assume at first glance. Rather, they seem to interfere with the reaction sequence of the uncatalyzed formation of 2-pyrazolines (Scheme 18) by preventing the 1-pyrazoline - 2-pyrazoline tautomerization from occurring. Thereby, the 1-pyrazoline has the opportunity to decompose purely thermally to cyclopropanes and formal vinylic C—H insertion products. This assumption is supported by the following facts a) Neither Mo(CO)6 nor Mo2(OAc)4 influence the rate of [3 + 2] cycloaddition of the diazocarbonyl compound to the alkene. b) Decomposition of ethyl diazoacetate is only weakly accelerated by the molybdenum compounds, c) The latter do not affect the decomposition rate of and product distribution from independently synthesized, representative 1-pyrazolines, and 2-pyrazolines are not at all decomposed in their presence at the given reaction temperature. 

It was demonstrated (83) that the reaction of dinitrostyrenes (28) with aryl diazo compounds RR CN2 afford nitronates (24 g) in good yields. These products contain the nitro group at the C-4 atom in the trans position with respect to the substituent at C-5 (if R =H). Since the reaction mechanism remains unknown, the direct formation of cyclic nitronates (24 g) from pyrazolines A without the intermediate formation of cyclopropanes also cannot be ruled out. 

Not much is known about the reactivity of the phosphinocarbene 2i. Problems arise, at least in part, from the high 1,3-dipolar reactivity of the diazo precursor li, which hides any carbene reactivity. Indeed, although li is stable in a toluene solution at 60°C for hours, the addition of an electron-poor olefin, such as a perfluoroalkyl-monosubstituted alkene, induces the exclusive formation of the thermodynamically more stable anti-isomer of the cyclopropane 14 (see Section V,B,3,a).36 This clearly demonstrates that the cyclopropanation reaction does not involve the carbene 2i, but that an initial [2 + 3]-cycloaddition occurs leading to the pyrazoline 13, which subsequently undergoes a classical N2 elimination.37... 

Lack of stereospecificity, extensive formation of olefinic products, and extensive tar formation limit the thermal decomposition of pyrazolines as a route to cyclopropanes.182 263 Light-induced decomposition of stereoisomeric pyrazolines establishes a method for the formation of cyclopropanes stereospecifically.222 Photolysis of 3-carbomethoxy-cis-3,4-dimethyl-l-pyrazoline (CCLI) produced cis-l,2-dimethylcycIopropane-l-carboxylate (CCLII) and without olefinic formation. Furthermore, irradiation of 3-carbomethoxy-trans-3,4-dimethyl-l-pyrazoline (CCLIII) gave [Pg.123]

Oxa-l -silabicyclo[ . 1,0 alkanes (n = 3 111 n = 4 113) were the only products isolated from the photochemical, thermal or transition-metal catalyzed decomposition of (alkenyloxysilyl)diazoacetates 110 and 112, respectively (equation 28)62. The results indicate that intramolecular cyclopropanation is possible via both a carbene and a carbenoid pathway. The efficiency of this transformation depends on the particular system and on the mode of decomposition, but the copper triflate catalyzed reaction is always more efficient than the photochemical route. For the thermally induced cyclopropanation 112 —> 113, a two-step noncarbene pathway at the high reaction temperature appears as an alternative, namely intramolecular cycloaddition of the diazo dipole to the olefinic bond followed by extrusion of N2 from the pyrazoline intermediate. A direct hint to this reaction mode is the formation of 3-methoxycarbonyl-4-methyl-l-oxa-2-sila-3-cyclopentenes instead of cyclopropanes 111 in the thermolysis of 110. 

In (39), we have an example of a stereospecific formation of a pyrazo-line. When pyrazolines are photolyzed, the elimination of nitrogen, if concerted, should be syn. This stereospecific product has been observed (McGreer and Wu, 1967). The pyrolysis of pyrazolines, if concerted, should be anti. It is not clear why this process turns out to be complex in (39), one alkene is formed stereospecifically by an anti hydrogen migration, but two isomeric cyclopropanes are formed. Crawford and Ali (1967), find rather different product patterns in the pyrolysis of 3-methyl and 3,4-dimethylpyrazolines, and give evidence for diradical intermediates. The general problem of unstable intermediates in a step-wise process will be discussed in a later section. 

The monosubstituted (trifluoromethyl)carbene has only been generated by irradiation of 2,2,2-trifluorodiazocthane, which is prepared by nitrosation of 2,2,2-trifluoroethylamine.1,3 175 The course of reactions with alkenes is dependent on concentration and pressure conditions. Thus, insertion products and pyrazolines may be obtained in competition with [2+1] cycloaddition giving the cyclopropane system. Yields of the latter are often moderate and, depending on singlet or triplet carbene formation, the reaction is not always stereoselective (Table 14). 

It is noteworthy that in the case of IV there is a unidirectional, regioselec-tive formation of the pyrazoline ring due to the more electrophilic character of the or carbon of the acrylate fragment than that of the /3-methyne. The regio-selectivity of this cycloaddition notwithstanding, pyrazolines usually collapse to cyclopropanes by exclusion of molecular nitrogen under the influence of moderate heat, such as in V leading to VI. 

Chiral electrophilic cyclopropanes (63) are prepared in high enantiomeric excess starting from butadiene-iron tricarbonyl complexes (60) containing a non-complexed double bond. Reaction with diazomethane and decomposition of the resulting pyrazolines (61) in the presence of Ce" gave the corresponding chiral cyclopropanes (62). Breakdown of the dienic substituent of electrophilic cyclopropane (62) by means of ozonization resulted in the formation of formyl-substituted electrophilic cyclopropane (63) still carrying the asymmetric centre (equation 10) " . ... 

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