Alkenes from diazoalkanes

The involvement of trimethylenemethane diradicals in deazetization of diazoalkane-allene adducts or trimethylene diradicals in the deazetization of the adducts of acyclic alkenes often leads to mixture of regioisomers and stereoisomers and from the standpoint of cyclopropane syntheses, this is undesirable. Far fewer problems of this type attend deazetization of the adducts of cyclic or polycyclic alkenes and, furthermore, even a modest amount of strain in the system activates the alkene to diazoalkane addition so that there is no need for activating substituents on the double bond. Cyclopropene is highly reactive towards diazoalkanes (see also Section 1.1.5.1.5.3.1.) and cycloaddition reactions of this type provide a ready entry into the bi-cyclo[1.1.0]butane series. The addition of diphenyldiazomethane to cyclopropene gave 4,4-diphenyl-2,3-diazabicyclo[3.1.0]hex-2-ene (1), which on photolysis gave a mixture of 2,2-diphenylbicyclo[1.1.0]butane (2) and 1,1-diphenylbuta-l,3-diene (3). ... 

The reaction system (6-37) includes the thermal azo-extrusion of a cyclic azo compound to a cyclopropane derivative and the direct formation of cyclopropanes, catalyzed by metal complexes. Synthetic routes to cyclopropane derivatives became an important subject in the last two decades, and one frequently used method is the 1,3-dipolar cycloaddition of a diazoalkane to an alkene followed by thermal or photolytic azo-extrusion of the 4,5-dihydro-3//-pyrazole formed to the cyclopropane derivative (6-37 A). This route can be followed in many cases without isolation, or even without direct observation, of the 4,5-dihydro-3//-pyrazole. Therefore, it is formally very similar to cyclopropane formation from alkenes with diazoalkanes, in which a carbene is first formed by azo-extrusion of the diazoalkane (see Sect. 8.3). As shown in pathway (6-37 B), this step can be catalyzed by copper, palladium, or rhodium complexes (see Sects. 8.2, 8.7, and 8.8). There are cases where it is not clearly known whether route A or B is followed. Scheme 6-37 also includes... 

The transition metal-catalyzed cyclopropanation of alkenes is one of the most efficient methods for the preparation of cyclopropanes. In 1959 Dull and Abend reported [617] their finding that treatment of ketene diethylacetal with diazomethane in the presence of catalytic amounts of copper(I) bromide leads to the formation of cyclopropanone diethylacetal. The same year Wittig described the cyclopropanation of cyclohexene with diazomethane and zinc(II) iodide [494]. Since then many variations and improvements of this reaction have been reported. Today a large number of transition metal complexes are known which react with diazoalkanes or other carbene precursors to yield intermediates capable of cyclopropanating olefins (Figure 3.32). However, from the commonly used catalysts of this type (rhodium(II) or palladium(II) carboxylates, copper salts) no carbene complexes have yet been identified spectroscopically. 

Some a-eliminations have already been discussed, like the formation of dichlorocarbene from chloroform and base. Others will be presented in certain contexts later. 1,3-Eliminations are mentioned in the preparation of 1,3-dipoles such as diazoalkanes or a-diazoketones and nitrile oxides (Chapter 15). Chapter 4 is limited to a discussion of the most important eliminations, which are the alkene-forming, /3-eliminations. Note that /3-Eliminations in which at least one of the leaving groups is removed from a heteroatom are considered to he oxidations. Eliminations of this type are therefore not treated here hut in the redox chapter (mainly in Section 17.3.1). 

The high nucleophilicity of a-selenoalkyllithiums towards carbonyl conqiounds, even those that are the most hindered or enolizable, such as 2,2,6-trimethyl- and 2,2,6,6-tetramethyl-cyclohexanone (Schemes 113 and 164), di-t-butyl ketone, pennethylcyclobutanone, peimethylcyclopenta-none (Schemes 113 and 187) °- and deoxybenzoin (Schemes 115, 116 and i65y 4 49 23 iqws the synthesis of related alkenes, epoxides and rearranged ketones which are not available from the same carbonyl compounds on reaction with phosphorus or sulfur ylides - or diazoalkanes. ... 

Table 1. Phosphoryl-Substituted Cyclopropanes from (Phosphoryl)diazoalkanes and Alkenes...

The other major limitation to the route is the problem of obtaining the desired precursor. Since this determines the scope of the reaction we will follow the pattern set in Houben-Weyl, Vol.4/3 and consider the syntheses according to the route by which the five-membered-ring diazene was derived, namely from (1) the addition of diazoalkanes to acyclic alkenes and allenes (2) the addition of diazoalkanes to cyclic alkenes and heterocyclic compounds (3) intramolecular addition of diazoalkanes to double bonds (4) cycloaddition reactions of dialkyl... 

Addition of diazoalkanes to a, -unsaturated amides and nitriles, although less frequently exploited than additions to esters, proceeds in a similar manner. Hence, the addition of diazomethane to 2-methylpropenenitrile (a-methylacrylonitrile) followed by thermal deazetization gave a good yield of 1-methylcyclopropanecarbonitrile (Houben-Weyl, Vol. 4/3, p 48). Similar problems with alkene formation are encountered to those noted in the ester series for example, in the thermolysis of 3,3-dicyano-4-isopropyl-4,5-dihydro-3/f-pyrazole 21, prepared from 20 by the addition of diazomethane. In this case, however, not only does the addition of copper(II) chloride accelerate the elimination of nitrogen, but it also reverses the product ratio in favor of the cyclopropane 23. " ... 

Considerably better yields are obtained when the alkene is significantly strained, as in the synthesis of [3]peristylane (5). Note in this case that flash-vacuum pyrolysis is the method of choice for the final step. The intramolecular addition step in the synthesis of ( —)-cyclo-copacamphene (8) and in a very similar synthesis of (+ )-cyclosativene presumably also gain assistance from ring strain. It should be noted that in these last two syntheses, the diazoalkane-alkene intramolecular cycloaddition succeeded where attempted carbene-alkene cycloadditions had failed. 

New evidence as to the nature of the intermediates in catalytic diazoalkane decomposition comes from a comparison of olefin cyclopropanation with the electrophilic metal carbene complex (CO)jW—CHPh on one hand and Rh COAc) / NjCHCOOEt or Rh2(OAc)4 /NjCHPh on the other . For the same set of monosubstituted alkenes, a linear log-log relationship between the relative reactivities for the stoichiometric reaction with (CO)5W=CHPh and the catalytic reaction with RhjfOAc) was found (reactivity difference of 2.2 10 in the former case and 14 in the latter). No such correlation holds for di- and trisubstituted olefins, which has been attributed to steric and/or electronic differences in olefin interaction with the reactive electrophile . A linear relationship was also found between the relative reactivities of (CO)jW=CHPh and Rh2(OAc) NjCHPh. These results lead to the conclusion that the intermediates in the Rh(II)-catalyzed reaction are very similar to stable electrophilic carbenes in terms of electron demand. As far as cisjtrans stereoselectivity of cyclopropanation is concerned, no obvious relationship between Rh2(OAc) /N2CHCOOEt and Rh2(OAc),/N2CHPh was found, but the log-log plot displays an excellent linear relationship between (CO)jW=CHPh and Rh2(OAc) / N2CHPh, including mono-, 1,1-di-, 1,2-di- and trisubstituted alkenes In the phenyl-carbene transfer reactions, cis- syn-) cyclopropanes are formed preferentially, whereas trans- anti-) cyclopropanes dominate when the diazoester is involved. 

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