Ketones base-promoted

With most ketones, base-promoted halogenation continues until the a carbon atom is completely halogenated. Methyl ketones have three a protons on the methyl carbon, and they undergo halogenation three times to give trihalomethyl ketones. 

Base promoted 1,4-additions ol nucleophiles (usually C) to a.6-unsalurated esters, ketones, nitnies, suHones, nitro-compounds often stereoselective addition. 

Base-promoted condensation of ketones with 3-nitroaniline results in the formadon of indoles. The reacdon proceeds in one pot via a NASH-type reacdon and subsequent cyclizadon fEq. 9.55. ... 

As an example of enolate-ion reactivity, aldehydes and ketones undergo base-promoted o halogenation. Even relatively weak bases such as hydroxide ion are effective for halogenation because it s not necessary to convert the ketone completely into its enolate ion. As soon as a small amount of enolate is generated, it reacts immediately with the halogen, removing it from the reaction and driving the equilibrium for further enolate ion formation. 

Problem 22.9 Why do you suppose ketone halogenations in acidic media referred to as being ackl-calalyzed, whereas halogenations in basic media are base-promoted In other words, why is a full equivalent of base required for halogenation ... 

Protoadamantanone has been prepared by the nitrous acid deamination of 2-amino-l-adamantanol (77%), by aprotic diazo-tization of endo-7-aminomethylbicyclo[3.3.1]nonan-3-one in benzene with an equivalent amount of acetic acid (67%), and by thermolysis of 1-adamantyl hypohalites followed by base-promoted cyclization of the resulting halo ketones (32-37%)." In spite of low and erratic yields, the last reaction sequence has provided the most convenient route to the protoadamantanes, since the other two approaches require lengthy syntheses of the starting materials. 

Carborundum, silver on, 27 10-12 3-Carboxy - 2,2,5,5,- tetramethylpyrrolidin-1-oxy m-nitrophenyl ester, enantiomeric specificity in reactions of cyclohexaamy-lose and cycloheptaamylose on, 23 233 Carboxylate ions, 32 117-118 Carboxybc acids a, 3-unsaturated, 25 109 hydrogenation of, 25 107-115 ketonization of, 24 35-37 Lewis base-promoted ruthenium catalysis, 32 389, 400... 

Darzens reaction of (-)-8-phenylmethyl a-chloroacetate (and a-bromoacetate) with various ketones (Scheme 2) yields ctT-glycidic esters (28) with high geometric and diastereofacial selectivity which can be explained in terms of both open-chain or non-chelated antiperiplanar transition state models for the initial aldol-type reaction the ketone approaches the Si-f ce of the Z-enolate such that the phenyl ring of the chiral auxiliary and the enolate portion are face-to-face. Aza-Darzens condensation reaction of iV-benzylideneaniline has also been studied. Kinetically controlled base-promoted lithiation of 3,3-diphenylpropiomesitylene results in Z enolate ratios in the range 94 6 (lithium diisopropylamide) to 50 50 (BuLi), depending on the choice of solvent and temperature. ... 

Base-promoted aminothiophene formation from ketone, a-active methylene nitrile and elemental sulfur. 

The empirical observation that (—)-sparteine 55 is necessary for catalysis implicates a base-promoted pathway in the mechanism. In the first step, a palladium alk-oxide is formed after alcohol binding, followed by p-hydride elimination of the alkoxide to yield a ketone product. On the basis of a kinetic study of the enantio-selective oxidation of 1-phenylethanol, it was revealed that (—)-sparteine plays a dual role in the oxidative kinetic resolution of alcohols, as a ligand on palladium and an exogeneous base " ... 

In an effort to obtain a salvinorin derivative possessing an oe-diol system which can be transformed into the dibenzoate ester required for the exciton chirality CD method, salvinorin A (1) or B (2) was treated with sodium borohydride in various protic solvents. The products having the la,2a-diol group were obtained in high yield. However, this reduction was accompanied by extensive isomerization at C-8. While mechanistic details for this unexpected observation remain to be established at this time, the isomerization at C-8 appears to be the result of the base-promoted clevage of the C-8/9 bond under the reaction conditions followed by the reclosure to provide the 8-epimer prior to the reduction of the 1-ketone. Furthermore, attempts to obtain the 1,2-dibenzoate derivative of the major reduction product 3 under various benzoylating conditions invariably produced only the 2-monobenzoate. 

The base-promoted bromination of ketones is a second-order process, first order in ketone and first order in base dius v = /c ketone base. The bromine concentration does not appear in die rate law that is, the reaction is zero order in [Br2]. 

Asymmetric aldol additions of geometrically defined trichlorosilyl enolates of ketones to aliphatic and aromatic aldehydes have been carried out uncatalysed, and with a chiral phosphoramide as Lewis base promoter.54 Significant differences in rates and diastereoselectivities are interpreted in terms of the changeover from a boat-like transition state, with pentacoordinate siliconate, to a chair-like transition state with hexacoordination. 

The Darzens reaction is the base-promoted generation of epoxides XIII from aldehydes (or ketones) XI and alkyl halides XII, the latter carrying an electron withdrawing group, for example the carbonyl, nitrile, or sulfonyl, in the a-position (Scheme 6.83) [188, 189]. It is, formally, addition of a carbene to the C=0 double bond (Scheme 6.83, path B) and thus complements oxygen atom transfer to olefins... 

Experimental results of an unprecedented haloform-type reaction in which 4-alkyl-4-hydroxy-3,3-difluoromethyl trifluoromethyl ketones undergo base-promoted selective cleavage of the CO-CF3 bond, yielding 3-hydroxy-2,2-difluoro acids and fluoro-form, have been rationalized using DFT (B3LYP) calculations.159 The solvent-induced effects on the two pathways, introduced within the SCRF formalism through PCM calculations, do not reverse the predicted preference of the CO-CF3 over the CO-CF2 bond cleavage in the gas phase. 

Liu L, Ji L, Wei Y (2008) Base promoted aerobic oxidation of alcohols to corresponding aldehydes or ketones catalyzed by CuCl/TEMPO. Catal Commun 9(6) 1379-1382... 

Reaction of N-substituted bromomethanesulfonamides with 2 equiv of potassium carbonate and an cr-haloketone, ester, or nitrile leads directly to the /3-sultams 187 substituted at the C-3 position by an EWG. This base-promoted condensation can be used with a-halo ketones, esters, and nitriles where a second Sn2 intramolecular displacement can operate in tandem fashion (Scheme 60). This domino alkylation sequence exhibits a reactivity order where ketone > nitrile > ester (Table 14). The process is particularly efficient when diethyl bromomalonate or 3-chloro-2-butanone are involved <2004CJC113>. 

A base-promoted cleavage of the hetero ring of the 4-oxo-3,4-dihydro-2/7-thiochromenium salt 299 results in the formation of an ethylsulfanylaryl vinyl ketone, while reaction with thiourea produces the thiochroman-4-one (Scheme 45) <1998T5599>. 

In contrast to what is observed in both neutral and acidic solutions, in basic medium there is no change in product distribution when the hydrogen availability is varied. This, and the fact that a,/3-unsaturated ketones are hydrogenated in preference to olefins in base but not in neutral media (18) indicate that a strongly adsorbed species, such as an enolate anion, is present in basic solutions of unsaturated ketones. If it is assumed that the enolate anion is involved in the base-promoted hydrogenation of unsaturated ketones and also that the initial adsorption of this species is the product-determining step in the reaction, a reasonable mechanistic hypothesis, based on that initially proposed by Wilds et al. (19) (see Scheme 3), can be put forth for this reaction. Such a process involves a hydride ion transfer from the catalyst to an adsorbed enolate... 

This mechanistic rationale can also be used to explain the product stereochemistry data from the base-promoted hydrogenation of other a,(3-unsaturated ketones as well. For example, if an angular methyl group were present in the heteroannular enolate depicted in Fig. 8, trans adsorption would be greatly favored. Thus, on hydride ion transfer from the catalyst and protonation from the solution, cis-product formation would predominate, as observed (9,10). 

Substituent effects on rate constants of base-promoted ionisation of ketones have led to the conclusion that an electron-withdrawing substituent increases the rate of ionisation, in agreement with the anionic character of the transition state. This is based chiefly on studies on halogenation and isotope exchange of aromatic ketones. Data on p-values observed by plotting ionisation rate constants versus Hammett -parameters (Table 3) for substituted... 

Mechanism 22-6 Base-Promoted Halogenation 1054 Mechanism 22-7 Final Steps of the Haloform Reaction 1056 Mechanism 22-8 Acid-Catalyzed Alpha Halogenation 1058 22-6 Alpha Bromination of Acids The HVZ Reaction 1059 22-7 The Aldol Condensation of Ketones and Aldehydes 1060... 

The base-promoted halogenation takes place by a nucleophilic attack of an enolate ion on the electrophilic halogen molecule. The products are the halogenated ketone and a halide ion. 

Because of this tendency for multiple halogenation, base-promoted halogenation is rarely used for the preparation of monohalo ketones. The acid-catalyzed procedure (discussed in Section 22-5C) is preferred. 

Q Give mechanisms for the acid-catalyzed and base-promoted alpha halogenations Problems 22-68 and 69 of ketones. Explain why multiple halogenations are common with basic catalysis, and give a mechanism for the haloform reaction. 

Addition of an Enolate to Ketones and Aldehydes (a Condensation) 1046 Substitution of an Enolate on an Ester (a Condensation) 1046 Base-Catalyzed Keto-EnolTautomerism 1047 Acid-Catalyzed Keto-EnolTautomerism 1047 Base-Promoted Halogenation 1054 Final Steps of the Haloform Reaction 1056 Acid-Catalyzed Alpha Halogenation 1058 Acid-Catalyzed Aldol Condensation 1063 1,2-Addition and 1,4-Addition (Conjugate Addition) 1085... 

Conversion of ketones into arylsulfbnylhydrazones allows preparation of the corresponding vinyl lithiums by base-promoted decomposition ofthe hydrazone. This is known as the Shapiro reaction. 

Synthetic thiazolium salts (86c), developed by Stetter and his co-workers and similar to thiamine itself (Stetter 1976), have been successfully used by Suzuki et al. for a diastereoselective intramolecular crossed aldehyde-ketone benzoin reaction in the course of an elegant synthesis of preanthraquinones (Hachisu et al. 2003). By using the highly functionalized isoxazole 104 as substrate, the tetracyclic a-hydroxy ketone 105 was obtained by base-promoted cyclocondensation in good yield. The high diastereoselectivity was induced by pre-existing stereocenters in the substrates (Scheme 28). 

This suggests that in the case that both intramolecular C- and 0-arylations are of geometrically equal possibility, the former preferentially takes place. The reaction of o-bromobenzaldehydes with dibenzylketones gives l,3-diaryl-2-naphthols that may be useful materials as bulky 0-ligands (Eq. 24) [62]. This cyclization involves palladium-catalyzed a-arylation and base-promoted dehy-drative condensation. Treatment of o-iodoanilines with ketones produces indole derivatives (Eq. 25) [63]. In this case, dehydrative condensation between the amino group and the carbonyl group occurs initially and the subsequent car-bopalladation (mechanism A) leads to the products. 

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