Coupling dicarbonylic

Alkenes in (alkene)dicarbonyl(T -cyclopentadienyl)iron(l+) cations react with carbon nucleophiles to form new C —C bonds (M. Rosenblum, 1974 A.J. Pearson, 1987). Tricarbon-yi(ri -cycIohexadienyI)iron(l-h) cations, prepared from the T] -l,3-cyclohexadiene complexes by hydride abstraction with tritylium cations, react similarly to give 5-substituted 1,3-cyclo-hexadienes, and neutral tricarbonyl(n -l,3-cyciohexadiene)iron complexes can be coupled with olefins by hydrogen transfer at > 140°C. These reactions proceed regio- and stereospecifically in the successive cyanide addition and spirocyclization at an optically pure N-allyl-N-phenyl-1,3-cyclohexadiene-l-carboxamide iron complex (A.J. Pearson, 1989). 

Treatment of O-silyl enols with silver oxide leads to radical coupling via silver enolates. If the carbon atom bears no substituents, two such r -synthons recombine to symmetrical 1,4-dicarbonyl compounds in good vield (Y. Ito, 1975). 

Formation o( oleltns by coupling or cross coupling of ketones, mediated by low valent titanium Also coupling ol enol ethers of 1,3-dicarbonyl compounds. 

The Hantzsch pyridine synthesis involves the condensation of two equivalents of a 3-dicarbonyl compound, one equivalent of an aldehyde and one equivalent of ammonia. The immediate result from this three-component coupling, 1,4-dihydropyridine 1, is easily oxidized to fully substituted pyridine 2. Saponification and decarboxylation of the 3,5-ester substituents leads to 2,4,6-trisubstituted pyridine 3. 

The coupling of arenediazonium compounds 1 to 1,3-dicarbonyl substrates 2 (Z = COR) is known as the Japp-Klingemann reaction As suitable substrates, /3-ketoacids (Z = COOH) and /3-ketoesters (Z = COOR) can be employed. As reaction product an arylhydrazone 4 is obtained. 

In general the reaction is conducted in aqueous solution under basic conditions—e.g. in the presence of KOH. The 1,3-dicarbonyl substrate is deprotonated to give the corresponding anion 5, which then couples to the arenediazonium species 1, to give the diazo compound 3 ... 

The Japp-Klingemann reaction is a special case of the aliphatic diazo coupling. For a successful reaction, the dicarbonyl substrate 2 should bear a sufficiently CH-acidic hydrogen. 

The reductive coupling of the dicarbonyl compound 6 induced by a low-valent titanium species gives initially the dihydroporphycenes 7 which then spontaneously aromatize in the presence of oxygen to yield the porphycenes 8. 

In azo couplings with carbonyl compounds, three tautomeric products are possible, compared with only two for phenols and aromatic amines (discussed in Section 12.1). The ketohydrazone 12.75 is most often dominant, but for easily enolizable 1,3-dicarbonyl compounds (X=CO-R and similar structures) the azoenol 12.76 is the major product. The azoketone 12.77 is often postulated as primary product, but has rarely been identified in an unambiguous fashion using modern methods. The CH2 group should be easily detectable in the lH NMR spectrum. 

The coupling reaction of arenediazonium ions with semidione radicals (12.84, obtainable by reduction of 1,2-diketones, 12.83) is also included here in the discussion of 1,3-dicarbonyl compounds, although it is a coupling with a nucleophilic radical and does not strictly belong in this context. The reaction (Scheme 12-43) was... 

In addition, Hashida et al. (1971 a) found a linear correlation between log k and the pof fifteen 1,3-dicarbonyl compounds. This indicates that in these cases the nucleophilicity and the basicity of the anions are closely related. The same result was obtained by Hashida et al. (1971b) for the azo coupling reactivity of substituted phenoxide ions. 

In 1976, Stetter extended the synthetic utility of the Breslow intermediate (1) as an acyl anion equivalent by showing that aldehydes could be coupled with Michael acceptors to generate 1,4-dicarbonyl compounds [55]. 

A couple of examples of (3-dicarbonyl systems are also given in Scheme 4.42. In each case, the second carbonyl gives rise to additional shielding. 

A McMurry coupling reaction involving 3-aza-1,5-dicarbonyl compounds gave 2,5-dihydro-3,4-diarylpyrroles <06SL490>. The latter were converted into the corresponding 3,4-diarylpyrroles by irradiation (Hg lamp, 500 W) in acetonitrile. 

The retro-Paal-Knorr ring opening reaction leading to 1,4-dicarbonyl compounds was accomplished by heating iV-substituted pyrroles in a citrate buffer <06SL1428>. The sequence was coupled with a forward Paal-Knorr reaction enabling the exchange of the N-substituent on pyrroles. 

An enantiospecific, gold-catalyzed pyrrole annelation reaction was utilized in a total synthesis of rhazinilam 95 <06JACS10352>. Specifically, treatment of allene 81 with gold triflate - triphenylphosphine led to the formation of annelated pyrrole 82, which was subsequently converted into 95. A gold-catalyzed direct coupling of pyrroles with 1,3-dicarbonyls led to the formation (3-(pyrrol-2-yl)enones <06ASC331>. 

Reductive Cyclizations of Dicarbonyl Compounds (Pinacol and McMurry Couplings) 529... 

The proposed catalytic mechanism for intramolecular McMurry reaction begins with the reduction of TiCl3 by zinc metal to generate the activated titanium species A-19. Reductive cyclization of the dicarbonyl substrate forms the McMurry coupling product, along with titanium oxide complex B-15. To close the catalytic cycle, the oxide complex B-15 is converted to TiCl3 by Me3SiCl (Scheme 63).8d,8e... 

Dicarbonyl coupling (8,483). This Ti-catalyzed coupling offers a useful route to cyclic sesquiterpenes such as humulene (4). The precursor is obtained by coupling a vinylic zirconium compound (1) with the u-allylpalladium complex (2) to give, after deprotection, the keto aldehyde 3 in 84% yield. This product couples to humulene as a single isomer in 60% yield. 

The most direct route to the 1,4-dicarbonyl equivalent required for the aldol condensation would be to couple the enol ether of an aldehyde with the enol ether of a ketone. However, this sequence proved impractical due to the hydrolytic instability of the ketone enol ether. Even after an extensive effort, the substrate for the electrolysis reaction could not be reproducibly prepared in high yield. These problems were readily avoided with the use of an allylsilane based... 

Symmetrical dissonant 1,6-dicarbonyl compounds (see Table 5.5) can also be prepared in good yields by either Cu(Bp4)2 or AgBF -induced coupling of... 

Examples of the synthesis of dissonant 1,4-dicarbonyl systems by oxidative coupling of the corresponding enolates have been described by Saegusa [35] (Scheme 5.26) ... 

The cationic iridium complex [Ir(cod)(PPh3)2]OTf, when activated by H2, catalyzes the aldol reaction of aldehydes 141 or acetal with silyl enol ethers 142 to afford 143 (Equation 10.37) [63]. The same Ir complex catalyzes the coupling of a, 5-enones with silyl enol ethers to give 1,5-dicarbonyl compounds [64]. Furthermore, the alkylation of propargylic esters 144 with silyl enol ethers 145 catalyzed by [Ir(cod)[P(OPh)3]2]OTf gives alkylated products 146 in high yields (Equation 10.38) [65]. An iridium-catalyzed enantioselective reductive aldol reaction has also been reported [66]. 

This protocol has been applied to the coupling of arene tellurolates with ( )-2-iodo-l-alkenyl sulphones, enolphosphonates, tosilates and triflates of )S-dicarbonyl compounds. 

McMurry, J. E. 1983. Titanium-induced dicarbonyl-coupling reactions. Accounts Chemical Research 16 405-11. 

Stetter expanded Umpolung reactivity to include the addition of acyl anion equivalents to a,P-unsaturated acceptors to afford 1,4-dicarbonyls Eq. 5a [57-60]. Utilizing cyanide or thiazolylidene carbenes as catalysts, Stetter showed that a variety of aromatic and aliphatic aldehydes act as competent nucleophilic coupling partners with a wide range of a,p-unsaturated ketones, esters, and nitriles [61]. The ability to bring two different electrophilic partners... 

Jprgensen has also developed a one-pot three component coupling of 1,3-dicarbonyl compounds, a,P-unsaturated aldehydes and primary amines to give a series of Hantzsch ester analogues [99],... 

Reduction of dicarbonyl compounds can be expected to lead to a cyclic 1,2-glycol formed by the intramolecular coupling of radical intermediates. 

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