1- Pyrazoline, ring contraction

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). 

Diazocarbonyl compounds readily undergo [3 + 2] cycloaddition to electron-poor alkenes 139). The 1-pyrazolines thus formed usually tautomerize to 2-pyrazolines if there is a hydrogen in an a-position to one of the nitrogen atoms otherwise, thermally induced ring contraction with evolution of nitrogen to give cyclopropanes can occur (Scheme 18). 

Cyclic diazoalkanes have been used to generate spirocyclopropanes via ring contraction of pyrazolines formed in the initial cycloaddition step. Two novel examples are the transformation of 3-diazo-2-nitromethylenepiperidine (16) into 5-aza-spiro[2.5]octane 17 (45) and the conversion of 1-diazo-2-methylenecyclo-propane (18) into methylene-spiro[2.2]pentane 19 (46) (Scheme 8.6). Related reactions have also been reported for diazocyclopropane (47) and diazospiropen-tane (48). 

In a novel total synthesis of the tricyclic sesquiterpene (—)-longifolene, an intramolecular diazoalkane cycloaddition to a cyclohexadienone ring followed by thermal ring contraction of the resulting pyrazoline gave the tricychc vinylcyclo-propane 261 and this constitutes the key steps in this synthesis (314) (Scheme 8.63). The interesting features of this sequence are the separation of dipole and dipolarophile by five atoms and the formation of a seven-membered ring in the cycloaddition step. 

It should be noted, however, that the 1,3-dipolar cycloaddition chemistry of diazo compounds has been used much less frequently for the synthesis of natural products than that of other 1,3-dipoles. On the other hand, several recent syntheses of complex molecules using diazo substrates have utilized asymmetric induction in the cycloaddition step coupled with some known diazo transformation, such as the photochemical ring contraction of A -pyrazolines into cyclopropanes. This latter process often occurs with high retention of stereochemistry. Another useful transformation involves the conversion of A -pyrazolines into 1,3-diamines by reductive ring-opening. These and other results show that the 1,3-dipolar cycloaddition chemistry of diazo compounds can be extremely useful for stereoselective target-oriented syntheses and presumably we will see more applications of this type in the near future. 

Pyrazolines, in general, undergo a photochemically induced ring contraction in solution to form a cyclopropane derivative and nitrogen. This process, unlike some equivalent thermal decompositions, is stereospecific, and methyI-as-3,4-dimethyl-l-pyrazoline-3-carboxyl-ate (88) is converted in high yield into methyl-as-1,2-dimethylcyclo-propane carboxylate (89).69 This route is of considerable preparative... 

Photochemical ring contraction of various substrates, e.g. cyclobutane-1,3-diones and 1 -pyrazolin-4-ones - gives either isolable cyclopropanes or cyclopropanones as intermediates which are usually intercepted as adducts or which fragment to alkenes and carbon monoxide. The photoextrusion process most often leads to fragmentation products. 

The compound class was further optimized towards antagonistic activity. A ring contraction to the pyrazoline scaffold and decoration of this ring with several substituents resulted in a series of compounds exemplified by 23. This displayed weak antagonistic activity in the MMTV reporter gene transactivation assay in CV-1 cells compared to mifepristone (RU-486) (Scheme 6.11). 

Not covered in this section are cyclopropanations that involve initial 1,3-dipolar cycloadditions of diazoalkanes to give pyrazolines, followed ring contraction and nitrogen extrusion. 

Thermolysis of the pyrazoline 1037 in chlorobenzene gave (76TL2513) triazinotetrazole 1038, which on further heating decomposed to 1040 and 1039. The reaction occurred by sequential ring expansion and contraction (Scheme 195). 

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