Carbonyl compounds, acid-promoted

One development involves the use of vitamin B 2 to cataly2e chemical, in addition to biochemical processes. Vitamin B 2 derivatives and B 2 model compounds (41,42) cataly2e the electrochemical reduction of alkyl haUdes and formation of C—C bonds (43,44), as well as the 2inc—acetic acid-promoted reduction of nitriles (45), alpha, beta-unsaturated nitriles (46), alpha, beta-unsaturated carbonyl derivatives and esters (47,48), and olefins (49). It is assumed that these reactions proceed through intermediates containing a Co—C bond which is then reductively cleaved. 

Polymerization of olefins such as styrene is promoted by acid or base or sodium catalysts, and polyethylene is made with homogeneous peroxides. Condensation polymerization is catalyzed by acid-type catalysts such as metal oxides and sulfonic acids. Addition polymerization is used mainly for olefins, diolefins, and some carbonyl compounds. For these processes, initiators are coordination compounds such as Ziegler-type catalysts, of which halides of transition metals Ti, V, Mo, and W are important examples. 

Titanium(IV) is a powerful but selective Lewis acid which can promote the coupling of allylsilanes with carbonyl compounds and derivatives In the presence of titanium tetrachlonde, benzalacetone reacts with allyltnmethylsilane by 1,4-addition to give 4-PHENYL-6-HEPTEN-2-ONE. Similarly, the enol silyl ether of cyclopentanone is coupled with f-pentyl chloride using titanium tetrachlonde to give 2-(tert-PENTYL)CYCLOPENTANONE, an example of a-tert-alkylation of ketones. 

Lewis acids, particularly the boron trifluroride diethyl ether complex, are used to promote the reaction between allyl(trialkyl)- and allyl(triaryl)stannanes and aldehydes and ketones52-54. The mechanism of these Lewis acid promoted reactions may involve coordination of the Lewis acid to the carbonyl compound so increasing its reactivity towards nucleophilic attack, or in situ transmetalation of the allyl(trialkyl)stannane by the Lewis acid to generate a more reactive allylmetal reagent. Which pathway operates in any particular case depends on the order of mixing of the reagents, the Lewis acid, temperature, solvent etc.55- 58. 

The majority of catalytic enantioselective allylation reactions involve the chiral Lewis-acid-catalysed additions of allylsilanes or allylstannanes to carbonyl compounds. Monothiobinaphthol has been used by Woodward et al. as a chiral promoter in the enantioselective catalytic allylation of aryl ketones with impure Sn(allyl)4, prepared from allyl chloride, air-oxidised magnesium and SnCl4. Therefore, the allylation of arylketones in these conditions was achieved very efficiently, since the corresponding allylic alcohols were formed in... 

Summary of the Relationship between Diastereoselectivity and the Transition Structure. In this section we considered simple diastereoselection in aldol reactions of ketone enolates. Numerous observations on the reactions of enolates of ketones and related compounds are consistent with the general concept of a chairlike TS.35 These reactions show a consistent E - anti Z - syn relationship. Noncyclic TSs have more variable diastereoselectivity. The prediction or interpretation of the specific ratio of syn and anti product from any given reaction requires assessment of several variables (1) What is the stereochemical composition of the enolate (2) Does the Lewis acid promote tight coordination with both the carbonyl and enolate oxygen atoms and thereby favor a cyclic TS (3) Does the TS have a chairlike conformation (4) Are there additional Lewis base coordination sites in either reactant that can lead to reaction through a chelated TS Another factor comes into play if either the aldehyde or the enolate, or both, are chiral. In that case, facial selectivity becomes an issue and this is considered in Section 2.1.5. 

A variety of electrophilic catalysts promote the addition of allylic silanes to carbonyl compounds.86 The original catalysts included typical Lewis acids such as TiCl4 or BFj.87 This reaction is often referred to as the Sakurai reaction. 

In 1991, Li and Chan reported the use of indium to mediate Barbier-Grignard-type reactions in water (Eq. 8.49).108 When the allylation was mediated by indium in water, the reaction went smoothly at room temperature without any promoter, whereas the use of zinc and tin usually requires acid catalysis, heat, or sonication. The mildness of the reaction conditions makes it possible to use the indium method to allylate a methyl ketone in the presence of an acid-sensitive acetal functional group (Eq. 8.50). Furthermore, the coupling of ethyl 2-(bromomethyl)acrylate with carbonyl compounds proceeds equally well under the same reaction conditions, giving ready access to various hydroxyl acids including, for example, sialic acids. 

Copper hydride species, notably Stryker s reagent [Ph3PCuH]6, are capable of promoting the conjugate reduction of a,( >-unsalurated carbonyl compounds [42], Taking advantage of this trustworthy method, Chiu et al. demonstrated in 1998 an intramolecular reductive aldol reaction in the synthesis of novel terpenoid pseudolaric acids isolated from Chinese folk medicine (Scheme 28) [43]. Two equivalents of [Ph3PCuH]6 enabled cycli-zation of keto-enone 104 to provide the bicyclic diastereomers 105 (66%) and 106 (16%). The reaction also was applied to the transformation of 107... 

The reaction can, however, be made preparative for (91) by a continuous distillation/siphoning process in a Soxhlet apparatus equilibrium is effected in hot propanone over solid Ba(OH)2 (as base catalyst), the equilibrium mixture [containing 2% (91)] is then siphoned off. This mixture is then distilled back on to the Ba(OH)2, but only propanone (b.p. 56°) will distil out, the 2% of 2-methyl-2-hydroxypentan-4-one ( diacetone alcohol , 91, b.p. 164°) being left behind. A second siphoning will add a further 2% equilibrium s worth of (91) to the first 2%, and more or less total conversion of (90) — (91) can thus ultimately be effected. These poor aldol reactions can, however, be accomplished very much more readily under acid catalysis. The acid promotes the formation of an ambient concentration of the enol form (93) of, for example, propanone (90), and this undergoes attack by the protonated form of a second molecule of carbonyl compound, a carbocation (94) ... 

Zeolites have also been described as efficient catalysts for acylation,11 for the preparation of acetals,12 and proved to be useful for acetal hydrolysis13 or intramolecular lactonization of hydroxyalkanoic acids,14 to name a few examples of their application. A number of isomerizations and skeletal rearrangements promoted by these porous materials have also been reported. From these, we can underline two important industrial processes such as the isomerization of xylenes,2 and the Beckmann rearrangement of cyclohexanone oxime to e-caprolactam,15 which is an intermediate for polyamide manufacture. Other applications include the conversion of n-butane to isobutane,16 Fries rearrangement of phenyl esters,17 or the rearrangement of epoxides to carbonyl compounds.18... 

Cycloadditions and cyclization reactions are among the most important synthetic applications of donor-substituted allenes, since they result in the formation of a variety of carbocyclic and heterocyclic compounds. Early investigations of Diels-Alder reactions with alkoxyallenes demonstrated that harsh reaction conditions, e.g. high pressure, high temperature or Lewis acid promotion, are often required to afford the corresponding heterocycles in only poor to moderate yield [12b, 92-94]. Although a,/3-unsaturated carbonyl compounds have not been used extensively as heterodienes, considerable success has been achieved with activated enone 146 (Eq. 8.27) or with the electron-deficient tosylimine 148 (Eq. 8.28). Both dienes reacted under... 

Considerable attention has been devoted to the preparation and chemistry of a,/3-unsaturated carbonyl compounds, which are valuable intermediates in organic synthesis [125]. Acid-promoted hydrolysis of alkoxyallenes has therefore frequently been employed to prepare a variety of functionalized a,/8-unsaturated carbonyl compounds [12b, 41, 44, 60, 126]. A recent example is illustrated in Scheme 8.54with C-l-silylated alkoxyallene 218 as a convenient starting material for the synthesis of bicyclo[5.4.0]undec-4-en-2-one 221. Sequential deprotonation and silylation at the terminal C=C bond efficiently transformed 218 into a 1,3-disilylated allene which was converted into the acryloylsilane 219 under acidic conditions. A [3 + 4] annula-tion of intermediate 219 with lithium dienolate 220 furnished bicydic compound 221 in good yield [127]. 

Hetero-Diels-Alder reactions of ,/i-unsaturated carbonyl compounds 186 with ethoxyallene are promoted by acid-free silica gel to give the [4+2]-adducts along with a small amount of [2 + 2]-adducts [151]. 

Trimethylsilylation of enolizable carbonyl compounds and alcohols has also been accomplished by the fluoride ion promoted reaction with hexamethyldisilane and ethyl trimethylsilylacetate [48, 49], with high stereospecificity giving Z-enol ethers from ketones [50]. l-Trimethylsilyl-(l-trimethylsilyloxy)alkanes, produced from the reaction of aldehydes with hexamethyldisilane, undergo acid-catalysed hydrolysis during work up to yield the trimethylsilylcarbinols [51]. In the case of aryl aldehydes, the initially formed trimethylsiloxy carbanion produces the pinacol (Scheme 3.1). 

The Pictet-Spengler reaction is the method of choice for the preparation of tetrahydro-P-carbolines, which represent structural elements of several natural products such as biologically active alkaloids. It proceeds via a condensation of a carbonyl compound with a tryptamine followed by a Friedel-Crafts-type cyclization. In 2004, Jacobsen et al. reported the first catalytic asymmetric variant [25]. This acyl-Pictet-Spengler reaction involves an N-acyliminium ion as intermediate and is promoted by a chiral thiourea (general Brpnsted acid catalysis). 

Tetrahydrofuran itself can be opened using either the stoichiometric or the catalytic version of arene-promoted lithiation, but both cases need the activation by boron trifluoride. The catalytic reaction was performed by treating the solvent THF 324 with the complex boron trifluoride-etherate and a catalytic amount (4%) of naphthalene. The intermediate 325 was formed. Further reaction with carbonyl compounds and flnal hydrolysis yielded the expected 1,5-diols 326 (Scheme 95), which could be easily cyclized to the corresponding substituted tetrahydropyrans under acidic conditions (concentrated FlCl). 

Actually, the conjugate addition of intermediate 331 to a,-unsaturated carbonyl compounds can be promoted not only by copper(I) salts but also with other Lewis acids, such... 

Epoxides can be isomerized to carbonyl compounds by Lewis acids.104 105 Boron trifluoride is frequently used as the reagent. Carbocation intermediates appear to be involved, and the structure and stereochemistry of the product are determined by the factors which govern substituent migration in the carbocation. Clean, high-yield reactions can be expected only where structural or conformational factors promote a selective rearrangement. 

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