Transition Metal-Catalyzed Reactions of Diazo Compounds

4 Transition Metal-Catalyzed Reactions of Diazo Compounds 

Palladium-catalyzed as well as photochemical reactions of diazoalkanes with optically pure oxazolidines derived from 1,2-amino alcohols and a,p-unsaturated tddehydes were found to be highly selective. 

In palladium-catalyzed reactions with diazomethane A -enoylsultams have been successfully used for the synthesis of cyclopropane carboxylic acid derivatives. The cleavage of the auxiliary was achieved by treatment of the cycloadducts with a. Ti(0 Pr)4, PhCHzOH b. Na0H/H20. 

In rhodium-catalyzed reactions of vinyldiazoesters with alkenes various chiral alcohols have been examined, whereby (.R)-pantolactone was found to be the best choice for the synthesis of trans cyclopropanecarboxylates. Cleavage of the auxiliary was achieved with 6N HCl. 

Nishida in The Chemistry of the Cyclopropyl Group, (Ed. Z. Rappoport), Part 1, John Wiley Sons, Chichester (1987), 307. 

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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. 

Tandem carbonyl ylide generation from the reaction of metallo carbenoids with carbonyl continues to be of great interest both mechanistically and synthetically. Effective carbonyl ylide formation in transition metal catalyzed reactions of diazo compounds depends on the catalyst, the diazo species, the nature of the interacting carbonyl group and competition with other processes. The many structurally diverse and highly successful examples of tetrahydrofuran formation cited in this mini-review clearly indicate that the tandem cyclization/cycloaddition cascade of metallo carbenoids has evolved as an important strategy in both carbo- and heterocyclic synthesis. 

Anciaux, A. J., Demonceau, A., Noeis, A. F., Hubert, A. J., Warin, R., Teyssie, P. Transition-metal-catalyzed reactions of diazo compounds. 2. Addition to aromatic moiecuies cataiysis of Buchner s synthesis of cycioheptatrienes. J. Org. Chem. 1981,46, 873-876. 

The metal-carbene complexes postulated as intermediates in transition metal-catalyzed reactions of diazo compounds are electrophilic species (especially if they are derived from a-diazocarbonyl compounds). Accordingly, electron-rich olefins are the most suitable substrates for copper-catalyzed cyclopropanations, whereas electron-poor substrates such as a,P-unsaturated carbonyl compounds in general are not sufficiently reactive. 

The transition-metal-catalyzed reaction of diazo compounds with olefins gives the [2 + l]-cycloaddi-... 

The transition-metal-catalyzed reaction of diazo compounds 702, which have a N—H or O—H bond at an appropriate position, gives nitrogen- and oxygen-containing heterocycles 703 (Scheme 2 1 8).293 Wang and Zhu demonstrated a convenient synthesis of the polyfunctionalized /Tfluoropyrroles by the rhodium-catalyzed intramolecular N—H insertion reaction.2933 The reaction of d-amino-y,y-difluoro-a-diazo-/Tketo esters 704 in the presence of Rh2(OAc)4 gave the... 

There are three leading reviews on metal carbenoid transformation, written by Doyle (1986), by Brookhart and Studabaker (1987), and by Maas (1987). They include aspects of synthesis and of mechanism. The more recent reviews in Trost and Fleming s Comprehensive Organic Synthesis were written by Helquist (1991, use of diazoalkanes) and by Davies (1991, diazo carbonyl compounds). The review of Ye and McKervey (1994) on a-diazocarbonyl compounds also contains examples of metal carbenoid transformations. The book of Hegedus (1994) contains representative syntheses of complex organic molecules obtained by transition metal-catalyzed reactions of diazo compounds. 

The transition-metal-catalyzed decomposition of diazo compounds is a very useful reaction for formation of substituted cyclopropanes. The reaction has been carried out with several copper salts.116 Both Cu(I) and Cu(II) triflate are useful.117 Several Cu(II)salen complexes, such as the V-/-butyl derivative Cu(TBS)2, have become popular catalysts.118 119 120 121 122... 

An elegant and efficient way for preparation of sulfonium ylides under mild conditions is the so-called Doyle-Kirmse reaction [25,26], which involves transition metal catalyzed decomposition of diazo compounds (usually a-diazocarbonyls) in the presence of sulfides. For the catalytic generation of matallocarbenes from diazo compounds, copper catalysts have traditionally been employed. More recently, rhodium and ruthenium compoimds were reported to be efficient catalysts, especially for the generation of sulfoniiun ylides [27-29]. 

Despite the volume of work concerned with metal-catalyzed decomposition of diazo compounds and carbenoid reactions 28>, relatively little work has been reported on the metal-catalyzed decomposition of sulphonyl azides. Some metal-aryl nitrene complexes have recently been isolated 29 31>. Nitro compounds have also been reduced to nitrene metal complexes with transition metal oxalates 32K... 

The detailed mechanism of transition metal-catalyzed cyclopropanation using diazo compounds as a carbene source is still covered by clouds of controversy, but it is generally accepted that the reaction proceeds through metal-carbenoid complexes,17-21 and the valency of the metal ions (M) changes with carbenoid formation (Scheme 85). 

A. Padwa, D. J. Austin, Ligand Effects on the Chemoselectivity of Transition Metal Catalyzed Reactions of a-Diazo Carbonyl Compounds, Angew. Chem. Int. Ed. Engl. 1994, 33, 801-811. 

Transition-metal-catalyzed reaction of a diazo compound with a C—H bond, which is located at an appropriate position in the diazo molecule, gives a C—H insertion product. The intramolecular reaction of diazo compounds which have one or more heteroatoms between a diazo group and a reactive C—H bond produces a new C—C bond through C—H inser-... 

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. 

Diazo compounds can be dediazonized by transition metal complexes to generate metallocarbenes, which are important intermediates in various transformations [45-48]. Since tosylhydrazones have been found to be readily available precursors of diazo compounds through the Bamford-Stevens reaction, a series of transition metal-catalyzed reactions of aldehyde tosylhydrazone salts in the presence of base and phase transfer catalyst (PTC) have been reported since 2000 [49-53]. It has been considered that metal carbenes generated from the in situ generated diazo compounds are involved in the catalytic cycle of these reactions -see (7). 

The common by-products obtained in the transition-metal catalyzed reactions are the formal carbene dimers, diethyl maleate and diethyl fumarate. In accordance with the assumption that they owe their formation to the competition of olefin and excess diazo ester for an intermediate metal carbene, they can be widely suppressed by keeping the actual concentration of diazo compound as low as possible. Usually, one attempts to verify this condition by slow addition of the diazo compound to an excess (usually five- to tenfold) of olefin. This means that the addition rate will be crucial for the yields of cyclopropanes and carbene dimers. For example, Rh6(CO)16-catalyzed cyclopropanation of -butyl vinyl ether with ethyl diazoacetate proceeds in 69% yield when EDA is added during 30 minutes, but it increases to 87 % for a 6 h period. For styrene, the same differences were observed 65). 

These reactions are covered in other chapters of Volume 11 (Chapters 11.06 and 11.07). This part deals only with examples which are in connection with other sections of this chapter. Additions of metallocarbenoids to unsaturated partners have been extensively studied. Most of the initial studies have involved the transition metal-catalyzed decomposition of cr-carbonyl diazo compounds.163,164 Three main reaction modes of metallocarbenoids derived from a-carbonyl diazo precursor are (i) addition to an unsaturated C-C bond (olefin or alkyne), (ii) C-H insertion, and (iii) formation of an ylid (carbonyl or onium).1 5 These reactions have been applied to the total synthesis of natural... 

The normal byproducts formed during the transition metal-catalyzed decomposition of diazoalkanes are carbene dimers and azines [496,1023,1329], These products result from the reaction of carbene complexes with the carbene precursor. Their formation can be suppressed by slow addition (e.g. with a syringe motor) of a dilute solution of the diazo compound to the mixture of substrate and catalyst. Carbene dimerization can, however, also be a synthetically useful process. If, e.g., diazoacetone is treated with 0.1% RuClCpIPPhjij at 65 °C in toluene, cw-3-hexene-2,5-dione is obtained in 81% yield with high stereoselectivity [1038]. 

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 metal-catalyzed reactions in general appear to involve carbenoid intermediates in which the carbene becomes bound to the metal.83 The metals which have been used most frequently in synthesis are copper and rhodium. 

Although the thermal decomposition of diazo compounds has received an extraordinary amount of attention, nevertheless, most of the studies were run in the presence of a catalyst (generally, copper metal or a copper salt), and therefore the catalyzed decomposition of diazo compounds by transition metal derivatives constitutes one of the most intensely investigated fields of organic chemistry. The use of such catalysts has resulted in a considerable improvement of the efficiency and selectivity of many carbene reactions (see Section 9). 

Similarly, the transition metal catalyzed cyclopropanation of alkenes or arenes with diazo compounds, in general, involves short-lived metal-carbene complexes which react with the alkene with concomitant reductive elimination of the metal fragment. Although not involving free carbenes, such reactions are covered fully in this section. 

Allyldiethylamine behaves similarly, but the yields are low since neither the starting amine nor the products are stable to the reaction conditions. For the efficiency of the cyclopropanation of the allylic systems under discussion, a comparison can be made between the triplet-sensitized photochemical reaction and the process carried out in the presence of copper or rhodium catalysts whereas with allyl halides and allyl ethers, the transition metal catalyzed reaction often produces higher yields (especially if tetraacetatodirhodium is used), the photochemical variant is the method of choice for allyl sulfides. The catalysts react with allyl sulfides (and with allyl selenides and allylamines, for that matter) exclusively via the ylide pathway (see Section 1.2.1.2.4.2.6.3.3. and Houben-Weyl, Vol. E19b, pll30). It should also be noted that the purely thermal decomposition of dimethyl diazomalonate in allyl sulfides produces no cyclopropane, but only the ylide-derived product in high yield.Very few cyclopropanes have been synthesized by photolysis of other diazocarbonyl compounds than a-diazo esters and a-diazo ketones, although this should not be impossible in several cases (e.g. a-diazo aldehydes, a-diazocarboxamides). Irradiation of a-diazo-a-(4-nitrophenyl)acetic acid in a mixture of 2-methylbut-2-ene and methanol gave mainly l-(4-nitrophenyl)-2,2,3-trimethylcyclo-propane-1-carboxylic acid (19, 71%) in addition to some O-H insertion product (10%). ... 

As with other diazo compounds, cyclopropanation with 1 or 2 can proceed either via a photo-chemically or thermally generated carbene, in a transition-metal-catalyzed reaction, or by [3 -I- 2] cycloaddition of the diazo function to the C-C double bond followed by nitrogen extrusion from the thermally unstable cycloadduct. 

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