Reactions of diazo compounds

5 Formation of metal-carbon bonds by other insertion reactions 

The addition of metal hydrides to carbon-carbon double or triple bonds is a special case of a very general reaction type, which involves the addition of a species A—B to an unsaturated system X=Y (or X=Y). 

Polar metal-carbon bonds, such as are found in the organometallic compounds of the most electropositive elements, can add to alkenes and alkynes, especially when the latter bear electron-withdrawing substituents, which either increase the polarity of the C=C or C=C bond or can stabilize a negative charge in the transition state. Thus butyllithium adds to diphenylethyne in diethyl ether, though not in pentane, and irflus-butylstilbene may be isolated after hydrolysis, showing that cis-addition occurs  

The polymerization of 1,3-butadiene is catalysed by butyllithium (p. 48). Oligomerization of ethene is effected by trialkylaluminiums (p. 80). Grignard reagents, however, do not normally add to alkenes or alkynes. 

The addition of M—N, M—P, M—0 and M—M bonds to alkenes and alkynes sometimes occurs, especially when these bonds are weak, as with the heavier elements such as Sn and Pb. Such reactions are favoured when the alkene or alkyne bears electron-attracting substituents such as —COOMe or —CN. 

The use of diazo compounds in the formation of metal-carbon bonds is conveniently divided into two sections—the reactions of (a) aliphatic and (b) aromatic diazo compounds. 

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Although the most general cycloaddition reaction of diazo compounds is that they react as 1,3-dipoles, recently some reactions have been reported in which they react as 1,2-dipoles,... 

Pyrido[],2-a]pyrimidine-3,7-dicarboxylate 396 was also obtained in the reaction of diazo compound 395 and methyl vinyl ketone in boiling benzene in the presence of a catalytic amount of ruthenium acetate. 

Aromatic diazonium compounds became industrially very important after Griess (1866a) discovered in 1861/62 the azo coupling reaction, by which the first azo dye was made by C. A. Martius in 1865 (see review by Smith, 1907). This is still the most important industrial reaction of diazo compounds. Hantzsch and Traumann (1888) discovered that a heteroaromatic amine, namely 2-aminothiazole, can also be diazotized. Heteroaromatic diazonium compounds were, however, only used for azo dyes much later, to a small extent in the 1930 s, but intensively since the 1950 s (see Zollinger, 1991, Ch. 7). 

Acid-Base and Isomerization Reactions of Diazo Compounds in Water... 

Carbonyl oxides (formed by the reaction of diazo compounds with singlet oxygen) may also be used to oxidize sulphoxides74. The corresponding sulphone is formed in reasonable yields and the reaction may be carried out in the presence of the sulphide functionality. The reaction proceeds as shown in equation (21) and involves initial nucleophilic attack by the carbonyl oxide on the sulphoxide sulphur atom followed by the facile departure of the carbonyl compound yielding the required sulphone. 

The reaction of diazo compounds with amines is similar to 10-15. The acidity of amines is not great enough for the reaction to proceed without a catalyst, but BF3, which converts the amine to the F3B-NHR2 complex, enables the reaction to take place. Cuprous cyanide can also be used as a catalyst. The most common substrate is diazomethane, in which case this is a method for the methylation of amines. Ammonia has been used as the amine but, as in the case of 10-44, mixtures of primary, secondary, and tertiary amines are obtained. Primary aliphatic amines give mixtures of secondary and tertiary amines. Secondary amines give successful alkylation. Primary aromatic amines also give the reaction, but diaryl or arylalkyl-amines react very poorly. 

Reaction of diazo compounds with a variety of transition metal compounds leads to evolution of nitrogen and formation of products of the same general type as those formed by thermal and photochemical decomposition of diazoalkanes. These transition... 

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). 

Metal catalysed or photochemically promoted reactions of diazo compounds with diketene gave cyclopropanespiro-P-lactones 25 and 26 <00JCS(P1)2109>. 

A different method of generating pyrazoles was reported by Aggarwal et al. and is shown in Scheme 47 [90]. Reaction of diazo compound 176 (derived from benzaldehyde 165) with an alkynylbenzene enabled cyclization to pyrazole 177. 

Furthermore, cyclopropane structures have often served as intermediates in organic synthesis. For these reasons, olefin cyclopropanation has proved to be a useful tool for synthetic organic chemists. This has led to the development of several methods for cyclopropanation reactions,91 including the metal-catalyzed reactions of diazo compounds with olefins, as well as the Simmons-Smith reaction. 

As with any modern review of the chemical Hterature, the subject discussed in this chapter touches upon topics that are the focus of related books and articles. For example, there is a well recognized tome on the 1,3-dipolar cycloaddition reaction that is an excellent introduction to the many varieties of this transformation [1]. More specific reviews involving the use of rhodium(II) in carbonyl ylide cycloadditions [2] and intramolecular 1,3-dipolar cycloaddition reactions have also appeared [3, 4]. The use of rhodium for the creation and reaction of carbenes as electrophilic species [5, 6], their use in intramolecular carbenoid reactions [7], and the formation of ylides via the reaction with heteroatoms have also been described [8]. Reviews of rhodium(II) ligand-based chemoselectivity [9], rhodium(11)-mediated macrocyclizations [10], and asymmetric rho-dium(II)-carbene transformations [11, 12] detail the multiple aspects of control and applications that make this such a powerful chemical transformation. In addition to these reviews, several books have appeared since around 1998 describing the catalytic reactions of diazo compounds [13], cycloaddition reactions in organic synthesis [14], and synthetic applications of the 1,3-dipolar cycloaddition [15]. 

The synthesis of thiiranes with subsequent elimination of sulfur is an important procedure for the creation of C=C bonds, especially for sterically crowded systems (47,48), in analogy to the Eschenmoser-sulfide-contraction reaction (116). The spontaneous elimination of sulfur was observed in the rhodium-catalyzed reaction of diazo compound 62, which gave rise to the formation of cyclopentenone derivative 63 (117) (Scheme 5.24). A synthesis of indolizomycin was published by Danishefsky and co-workers (118) and involved a similar annulation step. In this case, however, the desulfurization reaction was achieved by treatment with Raney Ni. 

In certain cases, 4,5-dihydro-1,2,3-diazaphospholes rather than 3,5-dihydro-1,2,4-diazaphospholes are formed from the [3-1-2] cycloaddition reaction of diazo compounds with phosphaalkenes. This regiochemistry was encountered in the reaction of (mesityl)P=CPh2 with diazodiphenylmethane and was attributed to steric factors (164). Electronic factors may explain the orientation found in the... 

Related investigations of the reaction of diazo compounds with alkyl-substituted thioketones [R2C=S, R = Et, Pr, i-Pi, f-Bu (203) 2,2,4,4-tetramethylcyclobutan-l-one-3-thione (204), and adamantanethione (205,206)] showed that the 3,3-dialkyl-... 

Second, the formation of the diazobenzazocine derivatives 264a-e represents an unprecedented reaction for intramolecular 1,3-dipolar cycloaddition reactions of diazo compounds. Note that diazo compounds such as 247a (305) and 248 (307) also give bridged diazabicyclo[n.2.1]alkenes rather than fused diazabi-cyclo[ .3.0]aUcenes upon treatment with Bp3-etherate, but these transformations... 

Mark Elliott was born in Doncaster. He studied in Loughborough, where he obtained a BSc in 1991 and a PhD in 1994 working with Prof. C. J. Moody on transition-metal-catalyzed reactions of diazo compounds. After postdoctoral work with Prof A. Pfaltz, initially in Basel under the auspices of a Royal Society European Exchange Fellowship, and later at the Max-Planck Institute in Miilheim, he returned to the UK in 1996 to take up his current position as lecturer in chemistry at Cardiff His reseach interests include asymmetric heterocyclic chemistry, asymmetric catalysis, and natural product chemistry. 

Reaction of diazo compounds with sulfur dioxide [37]. 

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