Diazo Ketone Decompositions

Any heterocycle containing the OCH=CH moiety can in principle extrude the superfluous fragment and form oxirene, as illustrated for a five-membered ring in Scheme 105. Probably the most propitious AB fragment would be nitrogen, but the required 1,2,3-oxadiazole (123) is unknown (see Chapter 4.21), probably because of ready valence tautomerization to diazoethanal (Scheme 106) (this approach has been spectacularly successful with the sulfur analogue of (2) (8UA486)). The use of (123) as an oxirene precursor is thus closely linked to the important diazo ketone decompositions discussed in Section 5.05.6.3.4(f). 

The cyclopropanation of alkenes, alkynes, and aromatic compounds by carbenoids generated in the metal-catalyzed decomposition of diazo ketones has found widespread use as a method for carbon-carbon bond construction for many years, and intramolecular applications of these reactions have provided a useful cyclization strategy. Historically, copper metal, cuprous chloride, cupric sulfate, and other copper salts were used most commonly as catalysts for such reactions however, the superior catalytic activity of rhodium(ll) acetate dimer has recently become well-established.3 This commercially available rhodium salt exhibits high catalytic activity for the decomposition of diazo ketones even at very low catalyst substrate ratios (< 1%) and is less capricious than the old copper catalysts. We recommend the use of rhodium(ll) acetate dimer in preference to copper catalysts in all diazo ketone decomposition reactions. The present synthesis describes a typical cyclization procedure. 

The cycloaddition reaction of dipoles has been known since the 18th century, later, Huisgen introduced the concept of a 1,3-dipole [30]. One of the earhest examples of copper(II) acetylacetonate [Cu(acac)2] catalyzed 1,3-dipole formation involved the controlled decomposition of an a-diazo ketone [31]. Some cases utilized copper as the metal species and demonstrated the feasibility of cycloaddition reactions and these 1,3-dipoles with dipolarophiles. These reactions set the stage for the evaluation of additional transition metals capable of catalyzing this transformation. The earliest example of rhodium(II)-catalyzed a-diazo ketone decomposition to form a 1,3-dipole was described by Teyssie and co-workers [32]. Despite this promising beginning, it was not until many years later that rhodium(II) was used generally for the formation of such 1,3-dipoles [6-12,21,29,30] (Fig. 1). 

More definitive evidence for the formation of an oxirene intermediate or transition state was presented recently by Cormier 80TL2021), in an extension of his earlier work on diazo ketones 77TL2231). This approach was based on the realization that, in principle, the oxirene (87) could be generated from the diazo ketones (88) or (89) via the oxocarbenes 90 or 91) or from the alkyne (92 Scheme 91). If the carbenes (90) (from 88) and (91) (from 89) equilibrate through the oxirene (87), and if (87) is also the initial product of epoxidation of (92), then essentially the same mixture of products (hexenones and ketene-derived products) should be formed on decomposition of the diazo ketones and on oxidation of the alkyne this was the case. 

The diazo ketone 3, when treated with silver oxide as catalyst, decomposes into ketocarbene 5 and dinitrogen Na. This decomposition reaction can also be achieved by heating or by irradiation with uv-light. The ketocarbene undergoes a Wolff rearrangement to give a ketene 6 ... 

An a-diazo ketone 1 can decompose to give a ketocarbene, which further reacts by migration of a group R to yield a ketene 2. Reaction of ketene 2 with water results in formation of a carboxylic acid 3. The Woljf re arrangement is one step of the Arndt-Eistert reaction. Decomposition of diazo ketone 1 can be accomplished thermally, photochemically or catalytically as catalyst amorphous silver oxide is commonly used ... 

A regio- and stereospecific synthesis of modhephene has also been achieved beginning with the Weiss-Cook reaction As illustrated in Scheme XCVII, cyclo-pentai -l,2-dione can be readily crait l into a-diazo ketone 8(M), copper-catalyz l decomposition of which delivers tricyclic ketone 801. Following the dimethylation of this intermediate, carbomethoxylation was accomplished to give 802 and provide... 

Cyclopentenones (6, 67-68). Details of the Lewis acid catalyzed decomposition of /3,y-unsaturated diazo ketones to form cyclopentenones have been published. Similar decomposition of y,<5-unsaturated diazo ketones to /Ly-unsaturated cyclo-hexenones is possible, but yields are significantly lower.5... 

This decomposition can be used to initiate cyclization of di- and triunsaturated diazo ketones to bi- and tricyclic ketones. However, the cyclization is only possible if the /3,y-double bond is di- or trisubstiluted (equation I). When the /Ly-double bond... 

The earliest methods for preparing cyclic a-diazo ketones involved the oxidation of the monohydrazones prepared from a-diketones, generally using mercuric oxide.7,8 Recent modifications of this procedure include the use of calcium hypochlorite in aqueous sodium hydroxide or activated manganese dioxide as oxidants.1 The latter reagent, especially, hoc ms preferable to mercuric oxide. The base-catalyzed decomposition of tile monotosylhydrazoneH of a-diketones has been... 

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