1.4- Dicaibonyl compounds

A simple synthetic method for 1,4-dicaibonyl compounds was introduced, based on the allylation of carbonyl compounds with allyl halide as a C3 component, followed by the palladium-catalyzed oxidation of the terminal alkenes (20) to methyl ketones (21). In this method, the allyl group is a synthetic equivalent of the 2-oxopropyl group (Scheme 5). This is a good anellation method for cyclopentenones. 

Addition of an acyl anion or its equivalmt to a,p-unsaturated ketones is an important synthetic mediod for 1,4-dicaibonyl compounds. In the palladium method for 1,4-dicartxHiyl compounds, a vinyl Grignard or vinyllithium reagent is used as a synthetic equivalent of the acetyl anion. Reaction of lithium divinylcuprate with 2-cyclohexenone (44) afforded 3-vinylcyclohexanone (45). which was oxidized to the 1,4-diketone (46 Scheme 12). ° ... 

Instead of a P-dicaibonyl compound, tiiphenylphosphoiane derivatives have been used to synthesize 5-aIkoxy-substituted pyrazoles (40). Thus, reaction of ethyl chloroglyoxalate phenyUiydtazone (49) with carbomethoxymethylene triphenylphosphorane (50) furnishes the 5-methoxypyrazole (51) in an 84% yield (eq. 10). 

The two most important structural features that stabilize the enol of a p-dicaibonyl compound ar e... 

Gawinecki and co-workers reported the structural determination of isomeric products from a similar reaction, the condensation of 1,2-diaminobenzenes 197 with 1,2-dicaibonyl compound 196 <99T8475>. The two different regioisomeric quinoxalines 198, which were produced in nearly equal amounts, were distinguished through the use of advanced NMR techniques including 2D z-gradient selected H, N HMBC. 

In this synthesis of 1,5-dicaibonyl compounds, 3-butenyl halide is behaving as a madced 3-oxobutyl reagent, and can be used as an equivalent of metiiyl vinyl ketone. These reactirais offer new anellation methods. Also 1,4-addition of the allyl group to enones, followed by oxidatitm. offers a conveiuent synthetic method for 1,5-diketone preparation. Lewis acid promoted Nfichael addition of allylsilane (48) to a,p-unsaturated ketones, followed by the palladium-catalyzed oxidation, affods 1,5-diketones (Scheme 17). 3... 

Peroxy acids normally form anhydrides when reacted with 1,2-dicaibonyl compounds in inert solvents or acids in alkaline or acidic media. An exception to this generality is the oxidation of the keto ester (74 Scheme 24), in which the ring oxygen facilitates tetrahydrofuran ring migration. Ohno and coworkers have exploited this reaction to develop a chemicoenzymatic approach from furan to the protected L-ribo-furanoside (75). 

As with other intramolecular ene reactions, this reaction is best suited to the preparation of cyclopentanes, but can also be used for the preparation of cyclohexanes. The reaction cannot be used for the formation of cyclopropanes or cyclobutanes since the unsaturated carbonyl compound is more stable than the ene adduct. 8,e-Unsaturated ketones (167) do not give cyclobutanes (171) by enolization to give (170) followed by a type I reaction but instead give cyclohexanones (169) by enolization to give (168) followed by a type II reaction. Alkynes can replace alkenes as the enophile. Enols can be prepared from pyrolysis of enol esters, enol ethers and acetals and from -keto esters and 1,3-dicaibonyl compounds. Tlie reaction is well suited to the preparation of fused or bridged bicyclic and spirocyclic compounds. Tandem ene reactions in which two rings are formed in one pot from dienones have also been described. The examples discussed below 2-i63 restricted to those published since Conia and Le Perchec s 1975... 

Synthesis o( fused cydopentanones (bicycio(3 3 0] octadiones) or of propeRanes from a-dicaibonyl compounds wa the double aldol condensation with ft-ketoesters 2... 

There are currently three general methods for the production of boron-stabilized carbanions, each of which has analogies in caibonyl chemistry. The cleavage of a 1,1-diboiylalkane by base readily yields the desired anion in a fashion similar to the base cleavage of a -dicaibonyl compound. Deprotonation a to a boron atom can be accomplished directly in special circumstances, as can the addition of an organo-metallic compound to a vinylborane, which is similar to conjugate addition to an a,p-unsaturated carbonyl compound. Each of these methods is treated in detail in Ae next three sections. 

Treatment of enolate anions derived from 3-dicarbonyl compounds with either ethynyl(phenyl)iodo-nium tetrafluoroborate (16) or with ethynyl-lead tetraacetate provides a neat and direct synthesis of a-ethynyl-l,3-dicaibonyl compounds. The former reaction probably proceeds via 1,2-hydrogen migration of an alkylidenecarbene intermediate (see Scheme 34). 

Keywords 1,3-dicaibonyl compound, a,)8-unsaturated ketone, Michael reaction, FeCl3 -H20, 1,5-dicaibonyl compound... 

The Pd-catalyzed annulation of 2-propargyl-l,3-dicaibonyl compounds with vinylic or aryl tiiflates or halides in the presence of potassium carbonate yields 2,S-disubstituted 3-acylfiirans <93TL28I3>. 

Ch. 24 Preparation of Quinoxalines from Primary Aromatic o-Diamino and 1,3-Dicaibonyl Compounds... 

Intramolecular addition of allylsilanes performed under chelation-controlled conditions represents an efficient method in which useful levels of stereoselectivity can be achieved. This process has been demonstrated for a variety of a-alkoxy, a, -dialkoxy and E-dicaibonyl compounds, including 3-keto esters, P-keto amides and 3-keto lactones. 

The addition of anions derived from P-dicaibonyl compounds to qx>xy>triflate derivatives like 59 in the presence of added base affords adducts 60. (R = alkyl, aryl or caiboxyalkyl, X = alkoxy). 

In a reaction leading to fused pyrimidine derivatives, the group led by Tu reported a catalyst-free, three-component reaction of aldehydes, p-dicaibonyl compounds and 2-aminobenzimidazole under microwave irradiation in water affording functionalized imidazopyrimidine derivatives 66 via a Hantzsch-like mechanism [55], as shown in Scheme 1.35. 

In a typical general experimental procedure by using traditional conditions, a solution of a-dicaibonyl compound, an aldeltyde, and urea in ethanol was heated under reflux in the presence of a catalytic amount of CeCl3.7H20 (25 mol%) for a certain period of time required to complete the reaction (TLC), resulting in the formation of dihydropyrimidinone derivatives. The reaction mixture was then poured into crashed ice and the solid product separated was filtered and reciystallized. 

Three resonance structures can be drawn for enolates derived from p-dicaibonyl compounds. 

The products can then be cleaved to give ketones or a-dicaibonyl compounds. Thus compounds such as (27) can serve not only as protected aldehydes but as synthetic functions in their own right. 

Kim DY (2000) A facile P-C bond cleavage of 2-fluoro-2-phosphonyl-l,3-dicaibonyl compounds on silica gel. Synth Commun 30 1205-1212... 

Scheme 2.88 The synthesis of quinoxalines 446 by the reaction of benzofuroxans 420 and 1,2-dicaibonyl compounds 446 mediated by SnCl2-2H20...

Carbon atoms of C-H bonds adjacent to heteroatoms can be employed in C-C bond forming reactions with 1,3-dicaibonyl compounds (Scheme 4-255). Nonacarbonyl-diiron is applied in catalytic amounts in the presence of di-tert-butyl peroxide (DTBP) to afford alkylated 1,3-dicarbonyl compounds in moderate to good yields. When a mixture of two diastereoisomers is obtained in 1 1 to 2 1 ratios. ... 

The Knoevenagel condensation with 1,3-dicaibonyls followed by a Michael reaction of a second molecule of the methylene compound, with or without addition of an amine or ammonia, may be used for the qualitative and quantitative determination of aldehydes even in the presence of ketones. Thus, cyclic 3-diketones such as dimedone (59) react with aldehydes but not with ketones in the absence of a catalyst. For the characterization the bis(2,6-dioxo-4,4-dimethylcyclohexyl)methanes (67) or the 4,6-dioxo-2,2,8,8-tetramethyl-l,2,3,4,5,6,7,8-octahydro-9F/-xanthene (68) may used. ... 

Some Amino Add-Specific Compounds. As listed in Table I, there were three pyrrolizines and one pyridoimidazole identified in the model systems. Pyrrolizines are a very in rtant class of volatile conpounds generated by the reaction of proline with reducing sugars. 2-Acetyl-pyrido(3,4-d)imidazole was another amino acid-specific Maillard reaction product identified in the model systems, which was derived fi om the reaction of histidine with dicaibonyls. 

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