Carbonyl compound dicarbonyl

The formation of Mannich bases 25 results from the reaction of (C5C)N)2 with enolizable ketones, aldehydes, and carboxylic esters (26-29) (Scheme 9.22) [42, 48, 49]. The reaction is reasonably interpreted in terms of the electrophilic addition of C59N+ intermediate to the enol form of the carbonyl compound. Dicarbonyl... 

Analysis Another lactone FGl reveals the true TM (A). Our normal discormection a of an a,p-unsaturated carbonyl compound gives us the 1,5-dicarbonyl compound (B) and the ketone (C) clearly derived from phenol. Alternatively we could disconnect bond b to the keto-ester (D) with the further discormection shown ... 

Vinyl ethers and a,P unsaturated carbonyl compounds cyclize in a hetero-Diels-Alder reaction when heated together in an autoclave with small amounts of hydroquinone added to inhibit polymerisation. Acrolein gives 3,4-dihydro-2-methoxy-2JT-pyran (234,235), which can easily be hydrolysed to glutaraldehyde (236) or hydrogenated to 1,5-pentanediol (237). With 2-meth5lene-l,3-dicarbonyl compounds the reaction is nearly quantitative (238). 

The cyclization of 6-aminouracils with three-carbon fragments such as a,B- unsaturated carbonyl compounds, /3-dicarbonyl compounds, acetylenic esters, etc., is dealt with as a [3+3] reaction (see Section 2.15.5.7.2). Reactions with alkoxymethylenemalonates and related compounds are regarded as proceeding through [6 + 0 (y)] cyclizations (see Section 2.15.5.4.2). 

Subsequent to Hantzsch s communication for the construction of pyridine derivatives, a number of other groups have reported their efforts towards the synthesis of the pyridine heterocyclic framework. Initially, the protocol was modified by Beyer and later by Knoevenagel to allow preparation of unsymmetrical 1,4-dihydropyridines by condensation of an alkylidene or arylidene P-dicarbonyl compound with a P-amino-a,P-unsaturated carbonyl compound. Following these initial reports, additional modifications were communicated and since these other methods fall under the condensation approach, they will be presented as variations, although each of them has attained the status of named reaction . 

The major developments of catalytic enantioselective cycloaddition reactions of carbonyl compounds with conjugated dienes have been presented. A variety of chiral catalysts is available for the different types of carbonyl compound. For unactivated aldehydes chiral catalysts such as BINOL-aluminum(III), BINOL-tita-nium(IV), acyloxylborane(III), and tridentate Schiff base chromium(III) complexes can catalyze highly diastereo- and enantioselective cycloaddition reactions. The mechanism of these reactions can be a stepwise pathway via a Mukaiyama aldol intermediate or a concerted mechanism. For a-dicarbonyl compounds, which can coordinate to the chiral catalyst in a bidentate fashion, the chiral BOX-copper(II)... 

The 1,4-addition of an enolate anion 1 to an o ,/3-unsaturated carbonyl compound 2, to yield a 1,5-dicarbonyl compound 3, is a powerful method for the formation of carbon-carbon bonds, and is called the Michael reaction or Michael addition The 1,4-addition to an o ,/3-unsaturated carbonyl substrate is also called a conjugate addition. Various other 1,4-additions are known, and sometimes referred to as Michael-like additions. 

The enolate anion 1 may in principle be generated from any enolizable carbonyl compound 4 by treatment with base the reaction works especially well with /3-dicarbonyl compounds. The enolate 1 adds to the a ,/3-unsaturated compound 2 to give an intermediate new enolate 5, which yields the 1,5-dicarbonyl compound 3 upon hydrolytic workup ... 

Strategy The overall result of an enamine reaction is the Michael addition of a ketone as donor to an cr,/3-unsaturated carbonyl compound as acceptor, yielding a 1,5-dicarbonyl product. The C—C bond made in the Michael addition step is the one between the a- carbon of the ketone donor and the /3 carbon of the unsaturated acceptor. 

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 precursors for >C6 acids (namely, >C6 oi-dicarbonyls) are assumed to form by aldol condensation of ot-dicarbonyl compounds with other carbonyl compounds (route 7), and termination of this oligomerization is... 

Aldehydes (see also Dicarbonyl Compounds, Unsaturated Carbonyl Compounds, etc.)... 

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). 

Because of the equilibrium between silylated alcohols and free carbonyl compounds, the reaction between silylated alcohols ROSiMe3 13 and free enolized 1,2-dicarbonyl compounds such as 403 in the presence of 1% CF3SO3H results, at... 

A mixture of 1,4-dioxane and water is often used as the solvent for the conversion of aldehydes and ketones by H2Se03 to a-dicarbonyl compounds in one step (Eq. 8.117).331 Dehydrogenation of carbonyl compounds with selenium dioxide generates the a, (i-unsaturated carbonyl compounds in aqueous acetic acid.332 Using water as the reaction medium, ketones can be transformed into a-iodo ketones upon treatment with sodium iodide, hydrogen peroxide, and an acid.333 Interestingly, a-iodo ketones can be also obtained from secondary alcohol through a metal-free tandem oxidation-iodination approach. 

Officially, the history of MCRs dates back to the year 1850, with the introduction of the Strecker reaction (S-3CR) describing the formation of a-aminocyanides from ammonia, carbonyl compounds, and hydrogen cyanide [4]. In 1882, the reaction progressed to the Hantzsch synthesis (H-4CR) of 1,4-dihydropyridines by the reaction of amines, aldehydes, and 1,3-dicarbonyl compounds [5], Some 25 years later, in 1917, Robinson achieved the total synthesis of the alkaloid tropinone by using a three-component strategy based on Mannich-type reactions (M-3CR) [6]. In fact, this was the earliest application of MCRs in natural product synthesis [7]. 

On the other hand, the use of [Rh(CO)2Cl]2 as a catalyst results in ring opening of the siloxycyclopropanes 13 to the silyl enol ethers 14 with high stereoselectivity [10]. The 2-siloxyrhodacyclobutane 15a is proposed to undergo j8-elimination to give jr-allylrhodium 16a followed by reductive elimination to the silyl enol ether 14a. 1-Trimethylsiloxybicyclo[n.l.0]alkanes serve as / -metallo-carbonyl compounds via desilylation with a variety of transition metals [11]. The palladium-catalyzed reaction of the siloxycyclopropanes 17 under carbon monoxide in chloroform provides a route to the 4-keto pimelates 18. In the presence of aryl triflates, the 1,4-dicarbonyl compounds 19 are... 

Alkylation of enolates with a-halo carbonyl compounds. (Formation of 1,4-dicarbonyl compounds)... 

In the hydroboration of terminal alkenes, carrying a ketone or aldehyde group, with a variety of borane reagents, dicyclohexylborane has been identified as the most efficient reagent. Analogous hydroboration of alkynyl ketones and alkynyl aldehydes with dicyclohexylborane yields the corresponding olefinic carbonyl compounds after protonation, or dicarbonyl compounds after oxidation. ... 

Hydroxymethylenecyclopropanols (340) have been shown" to be intermediates in the photochemical rearrangement of a, -unsaturated carbonyl compounds (339) to 1,4-dicarbonyl compounds (341). The products are eventually obtained by double tautomerization of the enol and cyclopropanol portions of (340). 

The majority of recent contributions for the conjugate addition of C-H acids to a,p-unsaturated carbonyl compounds catalysed through iminium ion intermediates have come from the laboratories of Jprgensen. The ease with which 1,3-dicarbonyl compounds and nitroalkanes can be deprotonated, together with the soft nature of the nucleophile mean this is a particularly facile reaction which conveniently leads to useful precursors for further synthetic manipulation. 

It should be noted that carbonyl compounds, more often aldehydes, are usual second reagent in both the groups. Other building-blocks in these multicomponent processes, leading to the formation of five-, six-, and seven-membered heterocycles, can be numerous acids and their derivatives, p-dicarbonyl compounds or other CH-acids, isocyanides, etc. At this, three-component reactions of ABC and ABB types [32] are the most typical for aminoazole, although some four-component ABCC processes were also published. 

Our own group is also involved in the development of domino multicomponent reactions for the synthesis of heterocycles of both pharmacologic and synthetic interest [156]. In particular, we recently reported a totally regioselective and metal-free Michael addition-initiated three-component substrate directed route to polysubstituted pyridines from 1,3-dicarbonyls. Thus, the direct condensation of 1,3-diketones, (3-ketoesters, or p-ketoamides with a,p-unsaturated aldehydes or ketones with a synthetic equivalent of ammonia, under heterogeneous catalysis by 4 A molecular sieves, provided the desired heterocycles after in situ oxidation (Scheme 56) [157]. A mechanistic study demonstrated that the first step of the sequence was a molecular sieves-promoted Michael addition between the 1,3-dicarbonyl and the cx,p-unsaturated carbonyl compound. The corresponding 1,5-dicarbonyl adduct then reacts with the ammonia source leading to a DHP derivative, which is spontaneously converted to the aromatized product. 

Jiang S, Agoston GE, Chen T, Cabal M-P, Turns E (1995) BF3 Et20-promoted allylation reactions of allyl(cyclopentadienyl)iron(II) dicarbonyl complexes with carbonyl compounds. Organometallics 14 4697 -709... 

If 1,3-dicarbonyl compounds are allowed to react with 2 the terminal attack is preferred if possible [22]. This is due to the thermodynamic stability of the corresponding cationic intermediates. a, 3-Unsaturated carbonyl compounds also... 

---