Diazo keto compounds

There are two important rhodium-catalyzed transformations that are broadly used in domino processes as the primary step. The first route is the formation of keto carbenoids by treatment of diazo keto compounds with Rh11 salts. This is then followed by the generation of a 1,3-dipole by an intramolecular cyclization of the keto carbenoid onto an oxygen atom of a neighboring keto group and an inter- or intramolecular 1,3-dipolar cycloaddition. A noteworthy point here is that the insertion can also take place onto carbonyl groups of aldehydes, esters, and amides. Moreover, cycloadditions of Rh-carbenes and ring chain isomerizations will also be discussed in this section. 

The strained bicyclic carbapenem framework of thienamycin is the host of three contiguous stereocenters and several heteroatoms (Scheme 1). Removal of the cysteamine side chain affixed to C-2 furnishes /J-keto ester 2 as a possible precursor. The intermolecular attack upon the keto function in 2 by a suitable thiol nucleophile could result in the formation of the natural product after dehydration of the initial tetrahedral adduct. In a most interesting and productive retrosynthetic maneuver, intermediate 2 could be traced in one step to a-diazo keto ester 4. It is important to recognize that diazo compounds, such as 4, are viable precursors to electron-deficient carbenes. In the synthetic direction, transition metal catalyzed decomposition of diazo keto ester 4 could conceivably furnish electron-deficient carbene 3 the intermediacy of 3 is expected to be brief, for it should readily insert into the proximal N-H bond to... 

The diazo function in compound 4 can be regarded as a latent carbene. Transition metal catalyzed decomposition of a diazo keto ester, such as 4, could conceivably lead to the formation of an electron-deficient carbene (see intermediate 3) which could then insert into the proximal N-H bond. If successful, this attractive transition metal induced ring closure would accomplish the formation of the targeted carbapenem bicyclic nucleus. Support for this idea came from a model study12 in which the Merck group found that rhodi-um(n) acetate is particularly well suited as a catalyst for the carbe-noid-mediated cyclization of a diazo azetidinone closely related to 4. Indeed, when a solution of intermediate 4 in either benzene or toluene is heated to 80 °C in the presence of a catalytic amount of rhodium(n) acetate (substrate catalyst, ca. 1000 1), the processes... 

A recent example of this intramolecular tandem transformation is the Rh(ii)-catalyzed reaction of diazo keto ester 71. Depending on the structure of the diazo compound, a push-pull dipole intermediate derived from 71 can be trapped either by a tethered vinyl group (when n = 0) or by an indole 7r-bond (when n=l) (Equation (11)). This result clearly demonstrates a critical role of the conformation of the cycloaddition transition state. 

As may now be expected from Cu(II) compounds, whose reduction to Cu(I) is a requirement for catalyst activation, product yield and enantioselectivity depend on the reagents and conditions used. Other diazo carbonyl compounds, including a (J-keto-a-diazo esters and oc-diazo esters, underwent intramolecular cyclopropanation in moderate-to-good yields, but with low enantiocontrol. 

Ytterbium triflate-catalyzed Michael addition of iV-methylindole to mesityl oxide 452 was carried out using a modification of the Kerr procedure (4% of Yb(OTf>3, 4equiv of compound 452) <1996SL1047, 1998CJC1256> to give the desired 4-(indol-3-yl)-4-methyl-2-pentanone 453 in 81% yield (Scheme 96) <2001TL6835>. Product 453 was converted into the a-diazo- )-keto ester 454 having an iV-methylindole unit. 

Phenols and Enolizable Keto Compounds. These compounds are coupled in alkaline (soda) solution as a rule. If the coupler is a sulfonic or carboxylic acid, or is soluble in water (e.g., resorcinol), it is dissolved directly in the required amount of soda solution. In other cases, the coupler is dissolved in the equivalent amount of dilute sodium hydroxide solution and the recaustic soda for complete solution in such cases, no more is used than is absolutely required. (Solution of the 2-hydroxyl-3-naphthoic acid arylides is greatly assisted by the addition of alcohol. In many cases, no other method of dissolving the coupler is known.) An unnecessarily large excess of alkali is to be avoided, except in special cases, since such an excess rapidly decomposes the diazo compound. It is desirable to use that amount of soda which will be converted to bicarbonate by the acid of... 

The following types of compounds undergo coupling reactions with diazo compounds (a) Phenols, (b) Enolizable keto compounds of an aliphatic character, having a reactive methylene group which may be part of an open chain or a ring system, either homocyclic or heterocyclic. This group of compounds may be represented by the formula ... 

Formation of keto compounds from aldehydes and aliphatic diazo compounds ethylene oxides may also be formed. 

The Mukaiyama-Michael addition of silyl enolates to a, -unsaturated thioesters is promoted by an SbCl5-Sn(OTf)2 binary catalyst to afford d-keto thioesters with high anti selectivity (Scheme 14.23) [60]. The successive treatment of lactones with a ketene silyl acetal and silyl nucleophiles in the presence of an SbCl5-Me3SiCl-Snl2 ternary catalyst yields a-mono- and a/ -disubstituted cyclic ethers (Scheme 14.24) [61]. SbFs promotes the condensation of a,y5-unsaturated aldehydes and ketones with a-diazo-carbonyl compounds to give cyclopropane derivatives in high isomeric purity [62]. 

Collomb, D., Deshayes, C., and Doutheau, A., Synthesis of functionalized phenolic derivatives via the benzannulation of dienylketenes formed by a thermal Wolff rearrangement of a-diazo-P-keto compounds. Tetrahedron, 52, 6665, 1996. 

The nucleophilic addition of Ti(IV) enolates of a-diazo-p-ketones 136 and 126 to N-tosylimine 182 and 184 is successfully promoted by the activation of TiCU to give b-(N-tosyl)amino substituted p-keto diazo carbonyl compounds 183 and 185.83... 

Transition metal-catalysed methods for carbenoid insertion into C-H bonds remain well documented. The asymmetric intramolecular Cu(II)-catalysed C-H insertion reactions of (i) a-diazo-/ -keto esters and phosphonates and (ii) a-diazo sulfones have been described. One can note that the optimal reaction conditions have been found to be quite similar regardless of the nature of the carbenoid precursor the best conditions featured CUCI2 as Cu(II)-source, bis(oxazoline) (68) as chiral ligand and sodium tetrakis[3,5-bis(trifluoromethyl)phenyl] borate (i.e., NaBARF) as additive. Under the so-optimized reaction conditions, each of these carbenoid sources have been eonverted into five-membered cyclopentanone-based derivatives (69), whereas a-sulfonyl diazo esters (70) have led to six-membered cyclic compounds (71), thus featuring a distinct but well-known selectivity. In a related work, the asymmetric C-H insertion cyclization of (70) to (71) has also been achieved under Rh(II)-catalysis, using a combination of Rh2(5-pttl)4 (72) as chiral catalyst and menthyl ester as chiral auxiliary. As already mentioned in the previous section, allene-containing substrates (49) have been shown to undergo an intramolecular C-H insertion process under Rh(II)-catalysis. ... 

Galiullina SV, Zakharova VM, Kantin GP, Nikolaev VA (2007) Chemistry of diazocarbonyl compounds XXX. Development of a synthetic approach to pyridazine structure via Wittig reaction of fluoroalkyl-containing diazo keto esters. Russ 1 Org Chem 43 607-614... 

From Diazo-keto-amides. A classical synthesis of 1,2,3-thiadiazoIes (3) involves the cyclization of a-diazo-/3-keto-amides (2) with hydrogen sulphide and catalytic amounts of ammonia. Under similar conditions, diazo-compounds of structure [4 R = Me or Et, RR = (CHj)6l gave the hydrazones (5) rather than the desired 1,2,3-thiadiazoles (3). ... 

Reaction with alcohols is general for diazo compounds, but it is most often performed with diazomethane to produce methyl ethers or with diazo ketones to produce ot-keto ethers, since these kinds of diazo compounds are most readily available. With diazomethane the method is expensive and requires great caution. It is used chiefly to methylate alcohols and phenols that are expensive or available in small amounts, since the conditions are mild and high yields are obtained. Hydroxy compounds react better as their acidity increases ordinary alcohols do not react at... 

Oxo-2,5-cyclohexadienylidene [83] was generated in solid argon at 9 K by irradiation of diazo compound [84] with visible light (A>495 nm) (Sander et al., 1988 Bucher and Sander, 1992 Bucher et al., 1992). The IR, UV, and esr spectra of [83] were in accord with a structure having a triplet state with one delocalized electron. In the IR spectrum of the carbene [83] the r (CO) mode was found at 1496 cm which indicates a bond order of the C—O bond considerably less than 2. The low-temperature reaction of carbene [83] with CO generated the keto-ketene [85]. Irradiation (A = 543 10 nm) of [83] led to its transformation into a very labile species, presumed to be [86], which rearranged back to [83] not only under UV or... 

Nor can there be any question of real tautomerism in the case of phenol. In its chemical properties phenol resembles the aliphatic enols in all respects. We need only recall the agreement in the acid character, the production of colour with ferric chloride, and the reactions with halogens, nitrous acid, and aromatic diazo-compounds (coupling), caused by the activity of the double bond and proceeding in the same way in phenols and aliphatic enols. The enol nature of phenol provides valuable support for the conception of the constitution of benzene as expressed in the Kekule-Thiele formula, since it is an expression of the tendency of the ring to maintain the aromatic state of lowest energy. In this connexion the hypothetical keto-form of phenol (A)—not yet obtained—would be of interest in comparison with... 

Bis-acceptor-substituted diazomethanes are most conveniently prepared by diazo group transfer to CH acidic compounds either with sulfonyl azides under basic conditions [949,950] or with l-alkyl-2-azidopyridinium salts [951] under neutral or acidic conditions [952-954]. Diazo group transfer with both types of reagents usually proceeds in high yield with malonic acid derivatives, 3-keto esters and amides, 1,3-diketones, or p, y-unsaturated carbonyl compounds [955,956]. Cyano-, sulfonyl, or nitrodiazomethanes, which can be unstable or sensitive to bases, can often only be prepared with 2-azidopyridinium salts, which accomplish diazo group transfer under neutral or slightly acidic reaction conditions. Other problematic substrates include amides of the type Z-CHj-CONHR and P-imino esters or the tautomeric 3-amino-2-propenoic esters, which upon diazo group transfer cyclize to 1,2,3-triazoles [957-959]. 

The benzoylphenylketene generated from 321 displayed a pronounced tendency to form chemospecific [2+4] Diels-Alder adducts with the C=N group of keto-imines. When compounds 328, derived from />-aminoacetophe-none and aromatic aldehydes, were reacted with a-diazo-/3-diketone 321, 2,3-dihydro-4//-l,3-oxazin-4-ones 329 were obtained via the addition of benzoylphenylketene to the C=N bond, and no formation of the corresponding C=0 adducts, 477-l,3-dioxin-4-ones, was observed (Equation 31) <2001J(P1)2266>. 

Diazocarbonyl compounds can be prepared on insoluble supports by diazo group transfer with sulfonyl azides or by diazotization of primary amines. Diazo group transfer from sulfonyl azides to 1,3-dicarbonyl compounds proceeds on cross-linked polystyrene as smoothly as in solution (Table 10.19). When 3-keto esters or amides are... 

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