1,3-dicarbonyl derivatives

Because the a-aminoketone is subject to self-condensation, the condensation with a P-dicarbonyl derivative (6) is usually carried out by generating the a-aminoketone in situ through reduction of an oximino derivative (7) 2iac ia glacial acetic acid is used as the reductant. For example, Knorr s pyrrole... 

A significant number of examples exist in which 1,3-dicarbonyl derivatives undergo reaction with thioglycolates to produce thiophenes. ° Such reactions are particularly effective when used in conjunction with P-ketoesters, as demonstrated by the preparation of 27. ... 

In a similar way, lipases catalyze Michael addition of amines, thiols [110], and even 1,3-dicarbonyl derivatives [111, 112] to a,/ -unsaturated carbonyl compounds (Scheme 5.21). 

Simon, C., Constantieux, T, Rodriguez, J. (2004) Utilisation of 1,3-Dicarbonyl Derivatives in Multicomponent Reactions. European Journal of Organic Chemistry, 4957M 980. 

At room temperature in methanol as solvent, complex OsH(t 2-H2BH2)(CO) (P Pr3)2 decomposes to give the dihydride-dihydrogen compound OsH2(t 2-H2) (CO)(P Pr3)2. If the decomposition, however, is carried out under reflux the cis-dihydride-ds-dicarbonyl derivative OsH2(CO)2(P Pr3)2 is formed.13... 

Ferreira developed a novel method for the preparation of masked 1,4-dicarbonyl derivatives for utilization in the Paal-Knorr synthesis of pyrroles <00SC3215>. In this process, the reaction between diazocompound 3 and n-butyl vinyl ether using dirhodium tetraacetate as catalyst provides dihydrofurans 4 which are easily converted into substituted... 

Substituted furan formation by an indirect cyclization of 1,4-dicarbonyl derivatives has also been adopted as a key step in the synthesis of 3-oxa-guaianolides. Although 1,4-dicarbonyl compounds have been traditionally considered as the direct precursors for furans, treatment of 1,4-dicarbonyl compounds having a tertiary acetoxy group with p-toluenesulfonic acid leads to only 11% yield of an alkenylfurans as derived from a cyclization/acetoxy-elimination route. The following scheme shows an alternative multi-step conversion of the 1,4-dicarbonyl that leads to a more acceptable yield of the acetoxyfuran . 

Cyclocondensation processes of p-dicarbonyl derivatives or their analogues are still widely employed for the synthesis of new isoxazoles. Non-proteinogenic heterocyclic substituted ct-amino acids have been synthesised using the alkynyl ketone functionality as a versatile building block ynone 2, derived from protected L-aspartic acid 1, reacted with hydroxylamine hydrochloride affording the isoxazole 3 with enantiomeric purity greater than 98% ee <00 JCS(P 1 )2311 >. 

The reaction with the siloxy derivative 29 is an interesting example because the product 30 is a 1,5-dicarbonyl derivative (Equation (36)).96 1,5-Dicarbonyls are classically prepared by a Michael addition, but the synthesis of 30 by a Michael addition is not possible because it would require addition to the keto form of 1-naphthol. The acetoxy derivative 31 resulted in a different outcome, leading to the direct synthesis of the naphthalene derivative 32 (Equation (37)).96 In this case, the combined C-H activation/Cope rearrangement intermediate was aromatized by elimination of acetic acid before undergoing a reverse Cope rearrangement. 

An electron-rich metal can deprotonate the dicarbonyl derivative, affording the hydridopalladium intermediate 23, which can undergo a Tr-allyl 24 formation through diene insertion (which can be assimilated to a hydridopalladation of olefin) (Scheme 7). The attack of the enolate to the -jr-allyl species occurs with good enantioselectivity in the presence of the chiral ligand. The final product 21 is released and the palladium(O) complex 22 is regenerated. 

The popular methodology for the construction of carbocyclic ring consists of the intramolecular aldol condensation of properly activated monosugars. This may be exemplified by transformation of 73 into the dicarbonyl derivative 74 which, upon treatment with base (or acid), provided the desired carbocycle (Fig. 26).39 Other differently substituted derivatives were also prepared by this approach.40... 

Alkenes have been oxidized to 1,2-diols (>90%) by catalytic amounts of the ammonium periodate in the presence of osmium, and stoichiometric amounts of the periodate cleave the diols to produce the dicarbonyl derivatives (>80%) [23,30]. The procedure appears, however, to be less effective than with the quaternary ammonium permanganate. 

Nishiguchi and coworkers were also able to use the Mn(OAc)3-mediated oxidation of 1,3-dicarbonyl derivatives as a method to effect furan formation (Scheme 13) [26]. The use of the mediator allowed for the earlier chemistry explored by Yoshida (Scheme 10) to be extended to the use of acyclic 1,3-dicarbonyl derivatives. 

Dicarbonyl derivatives from aldehydes and a,P-unsaturated ketones. The thi-azolium catalyst serves as a safe surrogate for CN. Also known as the Mi-chael-Stetter reaction. Cf. Benzoin condensation. 

DLSA are rigid diols. They have the same skeleton as isosorbide and LAGA. For instance, 1,4 3,6-dilactone of mannosaccharic acid is a dicarbonyl derivative of iso-mannide and monocarbonyl derivative of the lactone of the anhydromannonic acid. Therefore, DLSA could find applications as diols and their polymers are expected to have similar properties to that of isosorbide and LAGA polymers. 

Some steps of the sequence proposed, of course, may be others, but key stages including formation of ot,p-unsaturated dicarbonyl derivative 16, cyclization into tetrahydropyrimidine 17, and dehydration are common in the most cases. 

Dealing with the synthesis of dihydropyridopyrimidinones, the procedure was quite similar to the precedent, involving 2,6-diaminopyrimidin-4(3//)-one as enaminocarbonyl partner, various 1,3-dicarbonyl derivatives, and either aliphatic or aromatic aldehydes in water under microwave irradiations (Scheme 11). Interestingly, the guanidine system was unreactive, and a library of tri- and tetracyclic dihydropyridopyrimidinone derivatives was chemoselectively synthesized in high yields and short reaction times from this environmentally friendly procedure. 

The Knoevenagel reaction consists in the condensation of aldehydes or ketones with active methylene compounds usually performed in the presence of a weakly basic amine (Scheme 29) [116], It is well-known that aldehydes are much more reactive than ketones, and active methylene substrates employed are essentially those bearing two electron-withdrawing groups. Among them, 1,3-dicarbonyl derivatives are particularly common substrates, and substances such as malonates, acetoacetates, acyclic and cyclic 1,3-diketones, Meldrum s acid, barbituric acids, quinines, or 4-hydroxycoumarins are frequently involved. If Z and Z groups are different, the Knoevenagel adduct can be obtained as a mixture of isomers, but the reaction is thermodynamically controlled and the major product is usually the more stable one. 

This selection of diverse MCRs developed in the last 5 years clearly illustrates the high synthetic potential of 1,3-dicarbonyl derivatives in heterocyclic chemistry. These very easily accessible and versatile substrates can be accommodated in many original synthetic pathways. Therefore, they have found numerous applications, especially for the synthesis of complex heterocyclic structures, allowing the facile... 

Simon C, Constantieux T, Rodriguez J (2004) Utilisation of 1,3-dicarbonyl derivatives in multicomponent reactions. Eur J Org Chem 4957 980... 

Gu Y, De Sousa R, Frapper P, Bachmann C, Barrault J, Jer me F (2009) Catalyst-free aqueous multicomponent domino reaction from formaldehyde and 1,3-dicarbonyls derivatives. Green Chem 11 1968-1972... 

Lieby-Muller E, Simon C, Imhof K, Constantieux T, Rodriguez J (2006) A multicomponent domino reaction and in situ aerobic oxidation sequence for the first one-pot synthesis of polycyclic benzimidazoles from 1,3-dicarbonyl derivatives. Synlett 1671-1674... 

E. J. Corey and D. Seebach, Synthesis of 1, n-dicarbonyl derivatives using carbanions from... 

Hydrazine hydrate reacts with a-hydroxyacids to give the A -aminodihydrotriazole which is diazotised with sodium nitrite in HCl to the 3,5-disubstituted triazole enantiomer (Scheme 24) <87H(26)989>. These triazoles were converted to macrocyclic derivatives (see Section 4.02.12.3). The ketals of a-oxoesters undergo the same series of reactions to give, after hydrolysis, the 3,5-dicarbonyl derivatives (Scheme 25) <92S398>. 

Table 14 Mono- and Di-substituted 1-Azaquinolizinium Perchlorates (255) Obtained by [3 + 3] Reactions using a Dicarbonyl Derivative (253) or a /3-Chlorovinyl Ketone (254) with a 2-Aminopyridine (Scheme 124)...

Treatment of a readily enolizable 1,3-dicarbonyl derivative with a mixture of diethylzinc and diiodomethane generates a 1,4-dicarbonyl by a chain extension process through the corresponding cyclopropanol derivative (equation 23) . Several enolizable starting materials such as / -ketophosphonates °, / -keto amides and amino acid skeletons have been subjected to these chain extension conditions. 

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