Cyclopropanes from pyrazolines

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. 

We will now briefly examine y-elimination and extrusion reactions. An example of the former is the formation of a cyclopropane from 1-pyrazoline initiated either by heat or light. Suggest a mechanism for this reaction. 

An example of a y-elimination reaction is the formation of a cyclopropane from 1-pyrazoline initiated either by heat or light. The initial biradical, which is formed by the loss of the nitrogen molecule, then closes the ring to give the cyclic product. The conversion of R-CO-R to R-R and C=0 is called a Norrish Type I reaction. In this case, the C C bonds on each side of the carbonyl group cleave, and the resultant radicals then combine and so effect the extrusion of the CO molecule. 

This reaction was first reported by Kishner in 1911. It is the preparation of cyclopropane derivatives by decomposition of pyrazolines formed from hydrazine and a,p-unsaturated ketones or aldehydes. Therefore, it is known as the Kishner reaction, Kishner decomposition, or Kishner method. In addition, this reaction has been modified to prepare pyrazoline intermediates from diazomethane and unsaturated carbonyl compounds, such as maleic and fumaric esters, resulting in an ester group in the trans position. However, when maleic anhydride or maleimide is used, the corresponding pyrazoline is formed with carbonyl groups in the cis configuration. It has been found that the stability of pyrazolines varies considerably, decomposing to cyclopropanes at different rates. Moreover, the transformation of pyrazolines into cyclopropanes can be catalyzed by a trace amount of mercuric ion. ... 

Irradiation (s. a. under lithium salt) Cyclopropanes from -pyrazolines... 

A variety of substituted diazoalkanes have been examined. Rodina et reported formation of a spiro pyrazoline 31 from the cyclic diazoketone 30. The product on further heating to 141°C loses 1 mole of N2 to yield a spiro cyclopropane derivative 32. 

The evidence appears to be consolidating against a di-n-methane mechanism for the thermal conversion of pyrazolines into cyclopropanes. From 2,3-diaza-bicyclo[3,2,0]hept-2-ene (94a), six products were obtained, and their relative yields changed with temperature. This suggested that all six were not obtained from a single common intermediate. By this thermolytic method,... 

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. 

This investigation of successive bimolecular reactions is analogous to that carried out on the successive unimolecular processes represented by equations (1.64a) and (1.64b). There an estimate was made of the internal excitation of cyclopropane from photolysis of 1-pyrazoline from their experiments, Endo et al concluded that the average recoil energy from (1.74) amounted to 84 1% of that reaction s exoergicity. 

The preparation of cyclopropane derivatives has been greatly facilitated by the development of carbene-type intermediates (see Chapter 13) and their ready reaction with olefins. The preparation of phenylcyclopropane from styrene and the methylene iodide-zinc reagent proceeds in only modest yield, however, and the classical preparation of cyclopropane derivatives by the decomposition of pyrazolines (first employed by Buchner in 1890) is therefore presented in the procedure as a convenient alternative. 

DCA reactions are an important means of synthesis of a wide variety of heterocyclic molecules, some of which are useful intermediates in multistage syntheses. Pyrazolines, which are formed from alkenes and diazo compounds, for example, can be pyrolyzed or photolyzed to give cyclopropanes. 

Isolable pyrazolines (183) are obtained from the (1,3-butadiene)phosphonic acid esters (182 X=S02Me, COOalkyl R "=H or Me R2=Me or Ph) (products from (182 X=CN) are thermo-labile) and diazomethane. Pyrolysis of the phosphorylated pyrazolines affords phosphonopentadienes rather than phosphono-cyclopropanes (contrast (184)) and with NaH give pyrazoles or pyrazolephbsphonic acid esters. 

Allyloxysilyl)diazoacetic esters 6 and the homologous butenyloxy derivative 9 undergo intramolecular cyclopropanation to form 7 and 10, respectively, when decomposed photochemically or by transition metal catalysis. The thermal reaction of 9 produces the same result, whereas the l-oxa-2-sila-3-cyclopentene 8 is formed from 6, presumably via a pyrazoline intermediate. 

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). 

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). 

Simultaneous occurence of the pyrazoline and carbenoid route is observed in the presence of bis(campherquinone-a-dioximato)cobalt(II) 95), but the cyclopropanes derived from ethyl diazoacetate and H2C=CHX (X = COOMe, CN) were obtained only in low yield. 

EvenPd(OAc)2 is not effective in catalyzing the cyclopropanation of a,P-unsaturated nitriles by ethyl diazoacetate. Instead, vinyloxazoles 92 are formed from acrylonitrile or methacrylonitrile by carbenoid addition to the CsN bond 143 Diethyl maleate and diethyl fumarate as well as polyketocarbenes are by-products in these reactions the 2-pyrazoline which would result from initial [3 + 2] cycloaddition at the C=C bond and which is the sole product of the uncatalyzed reaction at room temperature, can be avoided completely by very slow addition of the diazoester... 

The photoelimination of nitrogen from 1-pyrazolines is one of the most thoroughly investigated photoreactions and it has been used extensively in the synthesis of cyclopropane derivatives.334 Both stereospecific and non-stereospedfic processes have been observed and these are believed, at least in simple 1-pyrazolines, to correspond to singlet and triplet excited states, respectively. Two reaction pathways have been proposed in the azoalkane 405335 direct excitation via a thermally activated S, state affords the C6H6 isomers 406 to 409, whereas triplet-sensitized excitation results in a tem-... 

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. 

---