Addition reactions continued ketones

In addition to the reductive coupling reaction of ketones, certain alcohols can also be reductively coupled using active uranium. Benzhydrol is coupled by active uranium to give TPA as the only coupled product. No TPE is seen. Under similar conditions, no coupling of benzyl alcohol is seen. The chemistry of the active uranium is under continued investigation. 

A dodecakis(NCN-Pdn) catalyst, synthesized in the group of Van Koten (Figure 4.24), was applied in the a continuous double Michael addition reaction between methyl vinyl ketone (MVK) and ethyl a-cyanoacetate.[34] The reaction was performed in the deadend reactor discussed in paragraph 4.2.1. Two catalytic runs were performed differing in the amount of catalyst and in the applied flow (both increased by a factor 2.5). Both runs showed high productivity for more than 24 h (Figure 4.25). 

There were two more stereocenters to set. It was expected that cuprates would add to the open face of the strained cyclobutene. The control of the other stereocenter was more problematic. One solution was to prepare an a-sulfonyl lactone. To this end, the ketone was converted to the secondary carbonate. As hoped, conjugate addition was followed by intramolecular acylation, but the reaction continued to full acyl transfer, to give 10. Fortunately, desilylation of 10 proceeded with concomitant lactonization. Desulfonylation then gave 2, which could be brought to high by recrystallization. 

Examples of nitrogen-containing heterocycle syntheses based on condensation reactions continue to be forthcoming. Examples include a tandem oxidation-annulation of propargyl alcohols in a one-pot synthesis of pyridines (Equation 148) <2003SL1443>, trifluoromethyl-substituted pyridines (Scheme 94) <2003S1531>, and standard malononitrile additions to a,/3-unsaturated ketones <1995JCM392>. 

In Chapter 21 we continue the study of carbonyl compounds with a detailed look at aldehydes and ketones. We will first learn about the nomenclature, physical properties, and spectroscopic absorptions that characterize aldehydes and ketones. The remainder of Chapter 21 is devoted to nucleophilic addition reactions. Although we have already learned two examples of this reaction in Chapter 20, nucleophilic addition to aldehydes and ketones is a general reaction that occurs with many nucleophiles, forming a wide variety of products. 

More remarkable are the reactions between ketone enolate ions and arynes generated by a complex base. Products derived using the aprotic solvent system differ considerably from those involving enolate ions in ammonia. In the protic solvent the aryl anion resulting from the addition of an enolate ion to an aryne is protonated and continued reaction is thereby prevented. Such protonation does not occur in the aprotic medium further reactions occur by intramolecular addition of the aryl anion to a carbonyl group, Scheme 5. Products obtained from acyclic ketones include... 

The poor yield in this conjugate addition is due primarily to the numerous competing reactions the ketone enolate can self-condense (aldol), can condense with the ketone of MVK (aldol), or can deprotonate the methyl of MVK to generate a new nucleophile. The complex mixture of products makes this n ute practically useless, (continued on next page)... 

Double Michael addition reactions between methyl vinyl ketone (MVK) and ethyl a-cyanoacetate under continuous conditions (dead-end reactor) were performed with a dodecakis (NCN-Pd") catalyst by the van Koten group (12). A high productivity and retention (99.5%) of the catalyst for more than 24 h was observed, but slow deactivation of the system occurred after a stable conversion level had been reached [23]. 

Oscillating chemical reactions continue to be investigated in sulphate media. Addition of a-monobromo-ketone, one of the products of the BrO 3-Ce v-cyclohexanone and Br03 -Ce -cyclopentanone systems has been shown to decrease and, in some instances, suppress the initial induction period. The inhibitory effects of Cl ions have also been described. In the gallic acid-bromate reaction catalysed by [Fe(phen)3]+/ + the enol is the reactive form of the organic substrate. The mechanism proposed is essentially that of... 

C-C cleavage of strained rings and ketones has been used to develop useful catalytic reactions. For example, vinylcyclopropanes and vinylcyclobutanes react with alkynes (Equation 6.66) to generate products from 5+2 and 6+2 addition processes that form seven- and eight-membered ring products by overall transformations that are homologs of the Diels-Alder reaction. " The mechanism of these catalytic reactions continues to be studied, but these reactions most likely occur by coordination of the olefin to rhodium and insertion of the metal into the cyclopropene or cyclobutane. Decarbonylation of dialkyl ketones, including relatively unstrained cyclic ketones, has been reported and most likely occurs by oxidative addition into the acyl-alkyl C-C bond, subsequent de-insertion of CO, and C-C reductive elimination. 

Peterson Alkenylation. The Peterson alkenylation reaction continues to be the major use of trimethylsilylmethyllithium (1) and converts a carbonyl group to a methylene (eq 1). Some enan-tioselectivity has been seen for the addition of 1 to benzaldehyde in the presence of chiral ligands. The ketone substrates can contain functional groups that are con5)atible with the basic conditions. The use of cerium(III) chloride to promote nucleophilic addition of 1 to an enolizable carbonyl compound has continued to prove advantageous. ... 

The lesser driving force of the aldol reaction of ketones is due to the greater stability of a ketone than an aldehyde [about 3 kcal mol (12.5 kJ mol )]. As a result, the aldol addition of ketones is endothermic. To drive the reaction forward, we can extract the product alcohol continuously from the reaction mixture as it is formed. Alternatively, under more vigorous conditions, dehydration and removal of water move the equilibrium toward the a, -unsaturated ketone (see margin). 

Introduce a solution of 15 g. of the diazo ketone in 100 ml. of dioxan dropwise and with stirring into a mixture of 2 g. of silver oxide (1), 3 g. of sodium thiosulphate and 5 g. of anhydrous sodium carbonate in 200 ml. of water at 50-60°. When the addition is complete, continue the stirring for 1 hour and raise the temperature of the mixture gradually to 90-100°. Cool the reaction mixture, dilute with water and acidify with dilute nitric acid. Filter off the a-naphthylacetic acid which separates and recrys-talhse it from water. The yield is 12 g., m.p. 130°. 

A solution of the ketone (10 mg) in dry dioxane (5 ml) is placed in the cathode compartment of the cell. Then 10% deuteriosulfuric acid in deuterium oxide (5 ml) is added slowly with stirring. A small additional quantity of dioxane may be necessary to maintain a homogeneous solution. The anode compartment is filled with an identical solvent mixture and the electrode inserted. The current is adjusted to 1(X) milliamps and the electrolysis is continued for 6-10 hr with rapid stirring. The progress of the reaction is... 

Hydroxy- 6-diazoandrost-5-en- l-one (96) To a stirred solution of 750 ml of methanol and 144 ml of 5 A sodium hydroxide is added 36 g (0.114 mole) of oximino ketone. Concentrated aqueous ammonia (56.6 ml, 0.850 mole) is then added followed by dropwise addition of 265 ml of cold 3 M sodium hypochlorite at a rate sufficient to maintain the temperature of the exothermic reaction mixture at 20 + 1° while cooling with an external ice bath. At temperatures below 20° appreciable amounts of a-mono- and a-dichloro ketones are obtained above 20° the chloramine decomposes before reacting with the oximino ketone. As soon as all of the sodium hypochlorite has been added, the ice bath is removed and the reaction mixture is allowed to warm to room temperature with continued stirring for 6 hr. The reaction mixture is diluted with an equal volume of water and extracted twice with... 

Continuing to age the reaction after the ester 33 had been consumed or adding more i-BuMgCI did not convert the ketone 3 to alcohol 61. We believed that the ketone was protected as the magnesium enolate 63, as shown in Figure 3.10. If this were true, then there must be a competition between deprotonation to give the enolate and addition to give the tertiary alcohol [18],... 

In total, over the past six years, the chelating P,N-ligands have shown considerable promise in a variety of enantioselective processes, including transfer-hydrogenation and hydrosilylation of ketones, hydroboration of alkenes, conjugate addition to enones and Lewis-acid catalysed Diels-Alder reactions, in addition to those described above.128,341 It is anticipated that this list will continue to grow, and... 

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