From Diazo-compounds

From Diazo Compounds. Addition of diazomethane or its substituted derivatives to double bonds is a standard approach for the preparation of cyclopropyl compounds. Pyrazolines may be intermediates in such reactions, but are often decomposed in situ without isolation. An example is the addition of diazomethane to the bis-ketal (92). The initially formed pyrazoline extrudes nitrogen at 450 C to give the cyclopropane (93 93%) which can be converted into the bis-aldehyde, or pyrolysed to ring-opened (94) and ring-expanded (95) products,  

The acid-induced reaction of aryldiazomethanes with olefins gives arylcyclo-propanes in addition to olefins and esters. The cyclopropanes are formed stereo-specifically and their yields are largest in reactions with olefins which on cation addition give secondary carbonium ion centres. The use of deuteriated acids leads to partial incorporation of deuterium in the cyclopropane adducts, whereas the use of [a- H]-phenyldiazomethane leads to partial loss of deuterium, suggesting a slow proton transfer from the acid to the diazo-compound a carbenoid rather than a free carbene appears to be involved. 

Addition of diazocyclopropane to steroidal olefins affords a variety of products, including spirocyclopropyl pyrazolines (from aP-unsaturated ketone functions). 

Rericha, Coll. Czech. Chem. Comm., 1974, 39, 2656. 

Alkoxycarbonylcarbenes, which are frequently used for cyclopropanation, have been reviewed by Marchand and Brockway.In conjunction with a copper complex of an asymmetric ligand, ethyl diazoacetate will condense with 2,5-dimethyl-hexa-2,4-diene to give optically active chrysanthemic ester.With a cobalt complex of (+ )-camphorquinone dioxime, enantioselectivities as high as 70 % could be obtained in the addition of diazoacetate to 1,1-disubstituted olefins. As would be expected, choice of both metal and chelate is critical in such asymmetric syntheses.  

From Diazo-compounds. The addition of diazo-compounds to olefins provides a routine method for the synthesis of cyclopropane derivatives. The reaction can pro- 

Homogeneous and heterogeneous catalysis of bismethoxycarbonylcarbene addition to olefins and the copper- and silver-catalysed decompositions of dimethyl diazomalonate all result in stereospecific cyclopropanation, although three-membered ring formation is accompained by significant amounts of allyic C—H insertions pro- 

Fischer, C. A. Grob, and H, Katayama, Helv. Chim. Acta, 1976,59, 1953. 

Kuwajima, Y. Higuchi, H, Iwasawa, and T. Sato, Chem. Letters, 1976, 1271. 

The use of chiral copper complexes in diazo-compound decompositions is a known route to optically active cyclopropanes and the potential of this process has been further exemplified.  

From Diazo-compounds. The Wolff rearrangement of a-diazo-ketones has been reviewed and a discussion of the Bamford-Stevens reaction and its associated mechanisms has appeared. The details of a cryochemical synthesis of cyclo-propanone from keten and diazomethane have been described, as have syntheses of cyclopropanone and cyclopropanone acetal. The photolysis of 1-diazobutane, resulting in methylcyclopropane, has been subjected to physico-chemical study. 

Phenylsulphinyldiazomethane (109) has now become available, and its decomposition in the presence of olefins leads to anti-cyclopropanes in a uniquely stereoselective 

Hagiwara, and T. Migiti, Bull. Chem. Soc. Japan, 1975,4i, 1951. 

Apart from routine applications to cyclopropane synthesis,the application of new catalysts to the decomposition of diazo-compounds has received considerable attention. The use of palladium acetate, originally reported in 1972 by Paulissen et o/., has been extended and applied to diazomethane and ethyl diazoacetate in the presence of aP-unsaturated carbonyl compounds. With a- and a-substituted aP-unsaturated ketones, stereospecific cis-addition occurs in excellent yields, but the catalyst proves to be ineffective with analogous trisubstituted olefins, as illustrated for the formation of (110) with diazomethane. The use of palladium chloride with the 

Radiichel, W. Skuballa, and H. VorbrOggen, Tetrahedron Letters, 1975, 629 B. RadOchel, U. Mende, G. Cleve, G.-A. Hoyer, and H. Vorbrflggen, ibid., p. 633. 

From Diazo-compounds. The routine cuprous-catalysed diazomethane cyclo-propanation method has been used on bicyclic and bridged olefins. With fneso-tetraphenylporphin, this procedure gave a single cyclopropane product, unlike the corresponding reaction with diazo-esters. Trishomobenzene has been prepared by multiple use of this diazomethane method. It was shown to be the trans-isomer (78) by n.m.r. spectroscopy in (78) there are seven types of H whereas in its cis-isomer there would be only three. Twelve isomeric products have been isolated by preparative g.l.c. from the reaction of diazomethane-Cu2Cl2 with biallenyl (79). Some of the products could be synthesized independently, otherwise structural assignments were based upon spectroscopic evidence. 

The Cu -induced process was chosen for reaction between ethyl diazoacetate and 1,4-dihydronaphthalene. This is the first stage of a good 

Besides the use of copper and its compounds, palladium dichloride, rhodium trichloride, tris(triphenylphosphine)rhodium(i) chloride, and palladium diacetate have been reported to be effective in catalysing the reaction of ethyl diazoacetate with styrene at room temperature. Of these, palladium diacetate is the most effective. 

Photolytic generation of carbenes for cycloaddition to olefins may be sensitized or direct. 1-Diazoindene (82) has been isolated for the first time 

A further example of the difference in reactions of direct and sensitized photolysis of the corresponding diazo-compounds, give non-stereospecific dimethyl diazomalonate in the presence of allyl alcohol gives O—insertion product (32%) as well as cycloaddition (25%), with sensitized irradiation there is 39% cycloaddition with little, if any, O—H insertion.  

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From Diazo Compounds via 1,3-Dipolar Cycloaddition. This method has been utilized widely in heterocychc chemistry. Pyrazohne (57) has been synthesized by reaction of ethyl diazoacetate (58) with a,P-unsaturated ester in the presence of pyridine (eq. 12) (42). 

This synthetic appproach has been used in a few cases for the preparation of pyridazines from diazo compounds and cyclopropenes. In general, cycloadducts (176) are formed first and these rearrange in the presence of acid or alkali to pyridazines (Scheme 98) (69TL2659, 76H(5)40l). Tetrachlorocyclopropene reacts similarly and it was found that the stability of the bicyclic intermediates is mainly dependent on substitution (78JCR(S)40, 78JCR(M)0582>. 

Ring enlargement of benzene derivatives by carbenes generated from diazo compounds (better in the presence of a Rh catalyst) Conversion of aldehydes to ketones by diazo compounds (Schlotterbeck) see also Ptau Planer... 

The sulfur ylide-mediated epoxidation of aldehydes has been thoroughly investigated [70, 71]. The chiral sulfur ylides reported by Aggarwal have been most broadly applicable, and a catalytic, asymmetric process yielding aromatic transepoxides has been developed [72]. In this process, the sulfur ylides are produced in situ from diazo compounds, generated in turn from tosylhydrazone salts (Scheme 9.15) [73],... 

Photo-de-diazoniation has found relatively little application in organic synthesis, as is clearly evident from the annual Specialist Periodical Reports on Photochemistry published by the Royal Society of Chemistry. Since the beginning of these reports (1970) they have contained a section on the elimination of nitrogen from diazo compounds, written since 1973 by Reid (1990). In the 1980s (including 1990), at least 90% of each report is concerned with dediazoniations of diazoalkanes and non-quinon-oid diazo ketones, the rest being mainly related to quinone diazides and only occasionally to arenediazonium salts. 

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 triplet state is usually the ground state for non-conjugated structures, but either species can be involved in reactions. The most common method for generating nitrene intermediates, analogous to formation of carbenes from diazo compounds, is by thermolysis or photolysis of azides.246... 

Durr, H. Triplet-Intermediates from Diazo-Compounds (Carbenes). 55, 87-135 (1975). 

Scheme 6/2.1. Rhodium(ll)catalyzed formation of carbenes from diazo compounds.

The examples described so far clearly show the value of the rhodium-catalyzed carbene transfer obtained from diazo compounds onto carbonyl and imino groups. However, the scope is even broader, as the formed carbene can also undergo an ad-... 

Besides the formation of carbenes from diazo compounds and the hydroformyla-tion, rhodium (as described previously for palladium) has also been used as catalyst in domino processes involving cycloadditions. Thus, Evans and coworkers developed a new Rh(I)-catalyzed [4+2+2] cycloaddition for the synthesis of eight-membered rings as 6/2-105 using a lithium salt of N-tosylpropargylamines as 6/2-104, allyl carbonates and 1,3-butadiene (Scheme 6/2.22) [221]. The first step is an al-... 

The photoelimination of nitrogen from diazo compounds provides a simple and versatile route for the generation of carbenes, and in certain instances, insertion reactions of carbenes can be employed in the synthesis of heterocycles. Carbenes are believed to be involved at least in part in the photochemically induced conversion of N,N-diethyldiazoacetamide (439) into the y-lactam 440 and the /Mactam 441,365 and a similar approach has been successfully employed in the synthesis of a carbapen-2-em366 and of 7-methylcephalosporin analogues.367 Carbene insertion of a different type has been observed on irradiation of the 6-anilino-5-diazouracils 442 to give the indolo[2,3-d]pyrimidines 443.368 Ring contractions in heterocycles... 

Ylides from R N2. This reagent is more effective than bis(acetylacetonate)-copper(II) (5, 244) for generation of carbenes from diazo compounds.2 The decomposition proceeds at a lower temperature, even at room temperature. The mild conditions are particularly useful in the preparation of heat-sensitive ylides, such as those of antimony, bismuth, and tellurium. 

The preparation of aromatic nitriles from diazo-compounds will be discussed later (p. 291). 

Triplet-Intermediates from Diazo-Compounds (Carbenes)... 

To summarize, it may be said that, broadly speaking, free carbenes are formed from diazo-compounds in photochemical and thermal reactions, whereas all other methods yield carbenoids. 

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