Diazo compounds synthetic applications

In this chapter the major emphasis is on the mechanistic aspects of dediazoniations because they are the basis for understanding the relative instability of diazo and diazonium compounds, and because a knowledge of these is helpful for optimizing synthetic applications of such compounds. Syntheses based on dediazoniation of arenediazonium salts are the subject of Chapter 10. 

These results can be interpreted in terms of competition between recombination of the diradical intermediate and conformational equilibration, which would destroy the stereochemical relationships present in the azo compound. The main synthetic application of azo compound decomposition is in the synthesis of cyclopropanes and other strained-ring systems. Some of the required azo compounds can be made by 1,3-dipolar cycloadditions of diazo compounds (see Section 6.2). 

Carbenes from Diazo Compounds. Decomposition of diazo compounds to form carbenes is a quite general reaction that is applicable to diazomethane and other diazoalkanes, diazoalkenes, and diazo compounds with aryl and acyl substituents. The main restrictions on this method are the limitations on synthesis and limited stability of the diazo compounds. The smaller diazoalkanes are toxic and potentially explosive, and they are usually prepared immediately before use. The most general synthetic routes involve base-catalyzed decomposition of V-nitroso derivatives of amides, ureas, or sulfonamides, as illustrated by several reactions used for the preparation of diazomethane. 

The synthetic utility of the ring expansion reaction was demonstrated by its application to the synthesis of thermolabile thiepins. When the diazo compound (66) obtained from benzo[c]thiopyrylium salt 65 was treated with palladium catalyst under the same conditions as in the case of 63, the product isolated was ethyl 2-naphthoate (68)48). The plausible reaction pathway is one comprising i) decomposition of 66 to the corresponding carbene intermediate, ii) ring expansion to the... 

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]. 

SYNTHETIC APPLICATIONS OF DIAZO COMPOUNDS 1.4.7A Dipolar Cycloaddition... 

Azo Coupling. The coupling reaction between an aromatic diazo compound and a coupling component is the single most important synthetic route to azo dyes. Of the total dyes manufactured, about 60% are produced by this reaction. Other methods include oxidative coupling, reaction of arylhydrazine with quinones, and oxidation of aromatic amines. These methods, however, have limited industrial applications. 

The metal-catalyzed decomposition of diazo compounds in the presence of carbonyl compounds is a well-established reaction to generate a carbonyl ylide intermediate. Several new developments have revolutionized this area of chemistry and are included in this review. Most notably, major advances have occurred in catalyst design, such that highly chemoselective, diastereoselect-ive and enantioselective carbenoid transformations can now be achieved. Furthermore, it has been recognized that a wide array of carbenoid structures can be utilized in this chemistry, leading to a broad range of synthetic applications. 

Transition metal-catalyzed esterification, includinglactonization 12SL357. Copper-catalyzed reactions of diazo compounds 12CC10162. Synthetic developments and applications of Ullmann-type reactions (formation of C—O, C—N, or C—S bonds) 130PP341. 

Intramolecular cyclopropanation is a simple and convenient method to produce bicyclic or tricyclic cyclopropanes when electrophiles, such as carbene precursors, and nucleophiles, such as alkenes, are present in the same molecule. The most significant advancement of this method is the formation of [3.1.0] and [4.1.0] bicyclic compounds from the cyclopropanation of allylic and homoallylic diazocarbonyl compounds. Some of the high stereoselective macrocyclic cyclopropanes, with up to 20-membered ring, can also be synthesized with this method. Among the catalysts used in these reactions, rhodium catalysts are most frequently used for their high yields and stereoselectivities. Their exceptional enantiocontrols in a variety of diazo-alkene substrates make them very popular in bioactive molecular synthetic applications. 

In order to expand the synthetic applicability of the methodology, Hu et al. decided to employ Michael acceptors as other type of electrophiles. They developed a three-component reaction between an aryl diazo compound, H O, and an enone, for the generation of y-hydroxyketones 126 bearing a quaternary carbon stereocenter, catalyzed by the system Rhj(OAc) (2mol%)/chiral Lewis acid (30mol%) [165a], Different Lewis acids were tested as cocatalysts, but only the Sc-, Yb-, and Zn-based catalysts proved to be active. 

Diazo compounds, with or without metal catalysis, are well-known sources of carbenes. For synthetic purposes a metal catalyst is used. The diazo compounds employed are usually a- to an electron-withdrawing group, such as an ester or a ketone, for stability. In the early days, copper powder was the catalyst of choice, but now salts of rhodium are favoured. The chemistry that results looks very like the chemistry of free carbenes, involving cyclopropanation of alkenes, cyclopropenation of alkynes, C-H insertion reactions and nucleophilic trapping. As with other reactions in this chapter, free carbenes are not involved. Rhodium-carbene complexes are responsible for the chemistry. This has enormous consequences for the synthetic applications of the carbenes - not only does the metal tame the ferocity of the carbene, but it also allows control of the chemo-, regio- and stereoselectivity of the reaction by the choice of ligands. 

Miller DJ, Moody CJ (1995) Synthetic applications of the O-H insertion reactions of carbenes and carbenoids derived from diazocarbonyl and related diazo compounds. Tetrahedron 51 10811-10843... 

While no unified synthetic approach to diazoalkanes can furnish all manner of substituted diazo compounds, the various methods and reagents surveyed here go far in enabling access to a rich inventory of these fascinating molecules. Further improvements will serve not only to popularize known applications of the neutral carbon nucleophiles, but also to spur interest in the development of related new reactions. Our focus in the next section is modernized, catalytic carbon insertion methodologies involving both stabilized and nonstabilized diazoalkane reagents. 

The synthetic applications of azidotrimethylsilane have been reviewed. (Azidochloromethylene)dimethylammonium chloride (35), a new reagent for the transfer of diazonium or diazo-groups, reacts with a variety of Cf/-acidic compounds by diazonium or diazo-group transfer. Thus, resorcinol reacts... 

Other applications of NHC-based rhodium catalysts include the cyclization of acetylene carboxylic acids, cyclopropanation of olefins with diazo compounds, or aryl-aryl cross-coupling combined with dynamic kinetic resolution with the help of a lipase or Beckmann rearrangement. Thus, the chemistry of NHC-Rh catalysts is rich and varied, and we expect new catalysts and patterns of reactivity in the years to come. These will provide new tools for synthetic organic chemistry. 

A second reaction which is a formal carbene addition is the metal-ion-catalyzed decomposition of diazo compounds. Although this reaction was originally carried out primarily with copper salts many other metal ions have been found to have related catalytic effects. Among those for which synthetic application have been... 

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