A-diazocarbonyl compounds

In the same area, good levels of enantioselectivity have been achieved in intramolecular C H insertion reactions of a-diazocarbonyl compounds... 

An intermolecular 1,3-dipolar cycloaddition of diazocarbonyl compounds with alkynes was developed by using an InCl3-catalyzed cycloaddition in water. The reaction was found to proceed by a domino 1,3-dipolar cycloaddition-hydrogen (alkyl or aryl) migration (Eq. 12.68).146 The reaction is applicable to various a-diazocarbonyl compounds and alkynes with a carbonyl group at the neighboring position, and the success of the reaction was rationalized by decreasing the HOMO-LUMO of the reaction. 

Synthesis of a-alkoxyketones from a-diazocarbonyl compounds and alcohols under the influence of copper or rhodium catalysts is well established as an alternative to the Lewis or proton acid catalyzed variant of this synthetic transformation. The sole recent contribution to the aspect of general reactivity deals with the competition between O/H insertion and cyclopropanation of unsaturated alcohols 162). The results... 

The metal-carbenoid intermediates, especially ones derived from a-diazocarbonyl compounds, are electrophilic, and electron-rich olefins in general react more easily with the carbenoid intermediates than electron-deficient olefins. For the interaction of metal carbenoid and olefin, three different mechanisms have been proposed, based on the stereochemistry of the reactions and the reactivity of the substrates (Figure 12) 21 (i) a nonconcerted, two-step process via a metallacyclobutane 226,264... 

In the late 1960s, methods were developed for the synthesis of alkylated ketones, esters, and amides via the reaction of trialkyl-boranes with a-diazocarbonyl compounds (50,51), halogen-substituted enolates (52), and sulfur ylids (53) (eqs. [33]-[35]). Only one study has addressed the stereochemical aspects of these reactions in detail. Masamune (54) reported that diazoketones 56 (Ri = CH3, CH2Ph, Ph), upon reaction with tributylborane, afford almost exclusively the ( )-enolate, in qualitative agreement with an earlier report by Pasto (55). It was also found that E) - (Z)-enolate isomerization could be accomplished with a catalytic amount of lithium phenoxide (CgHg, 16 hr, 22°C) (54). 

Ylide formation, and hence X-H bond insertion, generally proceeds faster than C-H bond insertion or cyclopropanation [1176], 1,2-C-H insertion can, however, compete efficiently with X-H bond insertion [1177]. One problem occasionally encountered in transition metal-catalyzed X-H bond insertion is the deactivation of the (electrophilic) catalyst L M by the substrate RXH. The formation of the intermediate carbene complex requires nucleophilic addition of a carbene precursor (e.g. a diazocarbonyl compound) to the complex Lj,M. Other nucleophiles present in the reaction mixture can compete efficiently with the carbene precursor, or even lead to stable, catalytically inactive adducts L M-XR. For this reason carbene X-H bond insertion with substrates which might form a stable complex with the catalyst (e.g. amines, imidazole derivatives, thiols) often require larger amounts of catalyst and high reaction temperatures. 

A density functional study has been made of the competition between Wolff rearrangement and [1,2]-H shift in /S-oxy-a-diazocarbonyl compounds. Silver-catalysed decomposition of a-diazoketones (88 n = 0), derived from A-tosyl a-amino acids in methanol, gave rise to mixtures of products of Wolff rearrangement (89) and direct insertion of the carbene into the NH bond (90). The -amino acid derived species (88 n = 1) gave rise to products of Wolff rearrangement. 

Diazoacetic esters, reactions with alkenes, alkynes, heterocyclic and aromatic compounds, 18, 3 26, 2 a-Diazocarbonyl compounds, insertion and addition reactions, 26, 2 Diazomethane ... 

The reaction of a-diazocarbonyl compounds with nitriles produces 1,3-oxazoles under thermal (362,363) and photochemical (363) conditions. Catalysis by Lewis acids (364,365), or copper salts (366), and rhodium complexes (367) is usually much more effective. This latter transformation can be regarded as a formal [3 + 2] cycloaddition of the ketocarbene dipole across the C=N bond. More than likely, the reaction occurs in a stepwise manner. A nitrilium ylide (319) (Scheme 8.79) that undergoes 1,5-cyclization to form the 1,3-oxazole ring has been proposed as the key intermediate. 

TABLE 8.3. SYNTHESIS OE 1,3-OXAZOEES EROM a-DIAZOCARBONYL COMPOUNDS AND NITRIDES... 

Ethers, sulfides, amines, carbonyl compounds, and imines are among the frequently encountered Lewis bases in the ylide formation from such metal carbene complex. The metal carbene in the ylide formation can be divided into stable Fisher carbene complex and unstable reactive metal carbene intermediates. The reaction of the former is thus stoichiometric and the latter is usually a transition metal complex-catalyzed reaction of a-diazocarbonyl compounds. The decomposition of a-diazocarbonyl compounds with catalytic transition metal complex has been the most widely used approach to generate reactive metal carbenes. For compressive reviews, see Refs 1,1a. 

Recent study on sulfonium ylide [2,3]-sigmatropic rearrangement has been focused on the development of new catalytic systems, including new catalysts and alternative carbene precursor other than commonly used a-diazocarbonyl compounds. Besides the most commonly used Cu(i) and Rh(ii) catalysts, Fe com-... 

Thiocarbonyl Ylide from Catalytic Reaction of a-Diazocarbonyl Compounds... 

Carbonyl ylides can be viewed as an adduct between a carbonyl group and a carbene and, in fact, some ylides have been prepared this way (see above). The application of carbonyl ylides to the synthesis of complex natural products has been greatly advanced by the finding that stabilized carbenoids can be generated by the decomposition of a-diazocarbonyl compounds with copper and rhodium complexes. The metallocarbenoids formed by this method are highly electrophilic on carbon and readily add nucleophiles such as the oxygen of many carbonyl derivatives to form carbonyl ylides. This type of reaction is in fact quite old with the first report being the addition of diazomalonate and benzaldehyde (33,34). 

When thiocarbonyl and a-diazocarbonyl compounds are combined, acyl-substituted thiocarbonyl ylides 158 are generated from a nonisolable 3-acyl-1,2,4-thiadiazoline 157 (Scheme 8.36). In addition to giving acylthiiranes 159 and 1,3-dithiolanes 160, dipoles 158 can also 1,5-cyclize to produce 1,3-oxathioles 161. Acyl-thiocarbonyl ylides derived from diazoketones [e.g., HC(0)C(N2)R, R = Ph, f-Bu (219,220) 2-diazocyclohexanone (221)] produce 1,3-oxathioles [e.g., 162 (220), Scheme 8.36], while those derived from diazoesters (218,222,223) lead to thiiranes by 1,3-cyclization. Ylides derived from a-diazocarboxamides form 1,3-oxathioles (e.g., 163) and thiiranes (e.g., 159, R1 = f-Bu, R2 = NMePh, R3 = R4 = Ph), depending on the nature of the substituents (220). A related 1,5-cyclization of an aminomethyl-thiocarbonyl ylide formed from dimethyl 3-anilino-2-diazobutanedioate was also reported (224). 

Photochemical or thermal extrusion of molecular nitrogen from a-diazocarbonyl compounds generates a-carbonylcarbenes. These transient species possess a resonance contribution from a 1,3-dipolar (303, Scheme 8.74) or 1,3-diradical form, depending on their spin state. The three-atom moiety has been trapped in a [3 + 2] cycloaddition fashion, but this reaction is rare because of the predominance of a fast rearrangement of the ketocarbene into a ketene intermediate. There are a steadily increasing number of transition metal catalyzed reactions of diazocarbonyl compounds with carbon-carbon and carbon-heteroatom double bonds, that, instead of affording three-membered rings, furnish five-membered heterocycles which... 

TABLE 8.3. SYNTHESIS OF 1,3-OX AZOLES FROM a-DIAZOCARBONYL COMPOUNDS AND NITRILES... 

Intramolecular cyclopropanations of a-diazocarbonyl compounds have been widely utilized as a means of constructing complex polycyclic compounds stereoselectively in short steps (e.g. equation 98)187"198. The choice of the ligand of the Rh(II) catalyst, Rh2L4,... 

Asymmetric cyclopropanations of alkenes and alkynes with a-diazocarbonyl compounds have been extensively explored in recent years and a number of very effective chiral catalysts have been developed2. Copper complexes modified with such chiral ligands as salicy-laldimines 38202,203, semicorrins 39204 208, bis(oxazolines) 40209-2" and bipyridines 41212 have... 

Cainelli and coworkers have reported the synthesis of a class of 4-(2-oxoethy-lidene)azetidin-2-ones (IV, Fig. 14) that could be carried out by a novel Lewis acid mediated reactions of 4-acetoxyazetidin-2-ones with a-diazocarbonyl compounds [277]. 

Direct aldol-type condensations of aldehydes with ethyl diazoacetate to give /S-hydroxy-a-diazocarbonyl compounds, R-CH(0H)-C(=N2)-C02Et, are catalysed by tetrabutylammonium hydroxide.155... 

Any pair of the three bonds in the cyclopropane ring such as 35a could now be disconnected but none is very favourable. We should much rather use a diazocarbonyl compound such as 42 to make the carbene. That will mean chain extension after cyclopropane formation. 

The intramolecular C-H insertion of a-diazocarbonyl compounds proceeds with excellent regioselectivity affording chroman-4-ones and with good enantioselectivity when Rh (II) carboxylates are used as the catalyst (95JCS(P1)1373). 

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