Diazoalkanes reaction with olefins

The transition metal-catalyzed reaction of diazoalkanes with acceptor-substituted alkenes is far more intricate than reaction with simple alkenes. With acceptor-substituted alkenes the diazoalkane can undergo (transition metal-catalyzed) 1,3-dipolar cycloaddition to the olefin [651-654]. The resulting 3//-pyrazolines can either be stable or can isomerize to l//-pyrazolines. 3//-Pyrazolines can also eliminate nitrogen and collapse to cyclopropanes, even at low temperatures. Despite these potential side-reactions, several examples of catalyzed cyclopropanations of acceptor-substituted alkenes with diazoalkanes have been reported [648,655]. Substituted 2-cyclohexenones or cinnamates [642,656] have been cyclopropanated in excellent yields by treatment with diazomethane/palladium(II) acetate. Maleates, fumarates, or acrylates [642,657], on the other hand, cannot, however, be cyclopropanated under these conditions. 

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. 

Besides Cu and Rh, various other metals are known to catalyze the decomposition of diazo compounds [6,7,8,9,10]. Palladium complexes, e.g., are efficient catalysts for the cyclopropanation of electron-deficient C-C double bonds with diazoalkanes [19,20, 21], in contrast to Cu and Rh catalysts which are better suited for reactions with electron-rich olefins. Unfortunately, attempts to develop chiral Pd catalysts for enantioselective cyclopropanation have not been successful so far [22]. More promising results have been obtained with cobalt and ruthenium complexes. These and other chiral metal catalysts, that have been studied besides Cu and Rh complexes, are discussed in chap. 16.3. The same chapter also covers a new direction of research that has recently been taken with the development of catalytic enantioselective Simmons-Smith reactions. 

The mechanism that has been proposed to explain the relative and absolute configurations of these examples is illustrated in Scheme 6.35 [128]. The catalyst, shown on the left of the scheme, is coordinatively unsaturated. Reaction with the diazoalkane affords the copper carbene shown at the top. The olefin approaches from the less hindered back side (note that the absolute configuration of the carbene carbon is set at this point), such that the indicated carbon (, which is the one most... 

The cyclometallated acetophenone oxime complex [PdCl C6H4C(Me)N-(0H) ]2 undergoes halide bridge splitting reactions with electron-rich olefins (8) to afford the carbene derivatives (70). The use of diazoalkanes as carbene ligand precursors has been reviewed. ... 

Diazoalkanes have also been widely utilized in 1,3-DC reactions with various olefins to construct pyrazolines and pyrazoles, which are easily converted to various types of nitrogen-containing molecules. Maruoka and coworkers developed the unprecedented enantioselective 1,3-DC of diazoacetates 46 and a-substituted acroleins 45 by using certain chiral titanium BINOLate Lewis acids as catalysts (Scheme 2.13) [24], Furthermore, Sibi evaluated a,p-unsaturated pyrazolidinone... 

Formation of esters by reaction of diazoalkanes with carboxylic acids is a mild and often quantitative procedure. It is particularly useful for the preparation of methyl and ethyl [4], benzyl [3, 58], and benzhydryl esters [45, 59, 60], although not on a large scale. The reaction is initiated by proton transfer from the carboxyl group and 0-alkylation is a competing reaction with phenolic acids. Diazoalkanes may also add to carbonyl [61] and olefinic linkages [62]. Thus the shikimic acid derivative (16) with a limited amount of diazomethane at low temperature gives the methyl ester (17) but with an excess of the reagent forms the isomeric pyrazolines (18 and 19) [63, 64]. 

Catalytic cyclopropanation of alkenes has been reported by the use of diazoalkanes and electron-rich olefins in the presence of catalytic amounts of pentacarbonyl(rj2-ris-cyclooctene)chromium [23a,b] (Scheme 6) and by treatment of conjugated ene-yne ketone derivatives with different alkyl- and donor-substituted alkenes in the presence of a catalytic amount of pentacarbon-ylchromium tetrahydrofuran complex [23c]. These [2S+1C] cycloaddition reactions catalysed by a Cr(0) complex proceed at room temperature and involve the formation of a non-heteroatom-stabilised carbene complex as intermediate. 

Most significant is the formation of 92 in all thermolysis reactions of 91. This result is consistent with the sequence 91 -> diazoalkane of type 94 — carbene 52 - bridgehead olefin 53 - carbene 54 — H shift to afford 92. Formation of olefin 93 is best interpreted by H shift from the methyl group of carbene 52 (X=/-Bu, Y=Me) to the carbonic carbon, whereas 95 is formed by insertion of the carbenic center of 52 (X=Y=r-Bu) into the C-H bond of the r-Bu group. 

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 diazoalkanes cyclopropanate olefins in the absence of any catalyst [658-660]. Thus, for instance, upon generation from A -cyclopropyl-A -nitrosourea at 0 °C diazocyclopropane spontaneously cyclopropanates methylenecyclopropanes [658]. Thermal, uncatalyzed cyclopropanations of unactivated olefines with aryldiazome-thanes can already occur at only slightly elevated temperatures (e.g. at 80 °C with 1-naphthyldiazomethane [661]). Henee, for enantioselective cyclopropanations with a chiral catalyst, low reaction temperatures should be chosen to minimize product formation via the uncatalyzed pathway. 

The most common byproducts encountered in cyclopropanations with diazoalkanes as carbene precursors are azines and carbene dimers , i.e. symmetric olefins resulting from the reaction of the intermediate carbene complex with the diazoalkane. The formation of these byproducts can be supressed by keeping the concentration of diazoalkane in the reaction mixture as low as possible. For this purpose, the automated, slow addition of the diazoalkane to a mixture of catalyst and substrate (e.g. by means of a pump or a syringe motor) has proven to be a very valuable technique. 

The problem of distinguishing between carbenoid and carbonium ion mechanisms of decomposition of diazoalkanes in protic media arises also in interpreting the base-induced decomposition of tosylhydrazones. In the original procedure for this widely-used reaction (W. R. Bamford and Stevens, 1952), the tosylhydrazone of a carbonyl compound is treated with the sodium salt of ethylene glycol in refluxing glycol. A mixture of olefins and alkoxyethanol is produced (equation 6). Many... 

In certain cases it has been shown that the rate of reaction of the a-haloalkyl derivative with a second reagent, such as an olefin or diazoalkane, is dependent upon the concentrations of both reactants (Blanchard and Simmons, 1964 Bethell and Brown, 1967). Such observations are consistent either with a one-step bimolecular reaction of the organo-metallic compound as such and the other reagent or with a rapid preequilibrium forming an intermediate, followed by a slow reaction of this intermediate with the second reactant. The latter alternative is represented in equation (14), in which b[olefin]Rate-determining reaction of an intermediate carbene... 

Addition reactions of diazoalkanes, especially diazomethane, diazopropane, diphenyl-diazomethane and ethyl diazoacetate, onto olefins, substituted with one or two electron-withdrawing groups take place very smoothly affording pyrazolines which upon heating or photolysis can give rise to the corresponding substituted cyclopropanes by elimination of nitrogen. 

In contrast to the wealth of chemistry reported for catalyzed reactions of diazocarbonyl compounds, there are fewer applications of diazomethane as a carbenoid precursor. Catalytic decomposition of diazomethane, CH2N2, has been reported as a general method for the methylenation of chemical compounds [12]. The efficacy of rhodium catalysts for mediating carbene transfer from diazoalkanes is poor. The preparative use of diazomethane in the synthesis of cyclopropane derivatives from olefins is mostly associated with the employment of palladium cat-... 

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