Carbonyl compounds, reaction with methylene equivalents

Reactions of carbonyl compounds with methylene equivalents leading to oxiranes (see Scheme 58) have been described [Pg.129]

Treatment of cyclopropane 1 with one equivalent of dry BiCl3 in methylene chloride results in an exothermic reaction producing monoakylbismuth derivative 16 in 80% yield Eq. (19) [11]. Addition of another equivalent of the cyclopropane then affords the dialkylated bismuth species 17, which in turn reacts with BiCl3 to give the monoalkyl species. IR absorptions due to the carbonyl groups indicate the chelate structures shown. The two propionate moieties in the dialkylated compound 17 give rise to two distinctive carbonyl bands in the IR spectrum,... 

Dihydro-l,4-benzoxazin-3-ones and -benzothiazin-3-ones are synthesized by the reductive cyclodehydration of 2-nitrophenoxyacetic acids or their thioxy equivalents and as these heterocycles have an active methylene group it is a simple matter to prepare 2-substituted derivatives by condensation reactions with aldehydes and other carbonyl compounds (Scheme 123) (79AP302). 

The a-alkylation of carbonyl compounds by their conversion into nucleophilic enoiates or enolate equivalents and subsequent reaction with electrophilic alkylating agents provides one of the main avenues for regio- and stereo-selective formation of carbon-carbon a-bonds. " Classical approaches to a-alkylation typically involve the deprotonation of compounds containing doubly activated methylene or methine groups and having p/iTa values of 13 or below by sodium or potassium alkoxides in protic solvents. Since these conditions lead to monoenolates derived from deprotonation only at the a-site of the substrate, the question of the regioselectivity of C-alkylation does not arise (however, there is competition between C- and 0-alkylation in certain cases). In more recent years, dienolates of p-dicarbonyl compounds have been utilized in -alkylations with excellent success. 

Methylene-l,4-alkanediols. The PdCl2-(PhCN)2 - SnCl couple transforms an allylic alcohol into an allyl anion equivalent. 2-Methylene-1,3-propanediol can be used to prepare 2-methylene-1,4-alkanediols on reaction with carbonyl compounds. 

In summary, most of the known synthetic routes to azaadamantanes depend on condensation of an amine or ammonia with a carbonyl compound or equivalent (aldehyde, ketone, ortho ester, acetal) or other active methylene compound, such as nitromethane. The syntheses of 10 and 13 employed bromo intermediates in displacement or addition reactions. 

Besides the aldol reaction to form y0-hydroxyketone, 1,3-Dipolar Cycloaddition can also form similar molecules. In addition to the Mukaiyama Aldol Reaction, the following are also similar or closely related to the aldol reaction the Claisen-Schmidt Condensation (the aldol reaction between benzaldehyde and an aliphatic aldehyde or ketone in the presence of relatively strong bases to form an o, )0-unsaturated aldehyde or ketone), the Henry Reaction (base-catalyzed addition of nitroalkane to aldehydes or ketones), the Ivanov Reaction (the addition of enediolates or aryl acetic acid to electrophiles, especially carbonyl compounds), the Knoevenagel Reaction (the condensation of aldehydes or ketones with acidic methylene compounds in the presence of amine or ammonia), the Reformatsky Reaction (the condensation of aldehydes or ketones with organozinc derivatives of of-halo-esters), and the Robinson Annulation Reaction (the condensation of ketone cyclohexanone with methyl vinyl ketone or its equivalent to form bicyclic compounds). 

Kinetic studies of the reaction of oxo(salen)chromium(V) triflate with alkynes suggest that a metallaoxetane or a chromium carbene acts as an intermediate in the reaction.326 The bridging methylene complexes, (THF)nClxMo(0) 2( X-CH2)2. are prepared by treatment of MoCly(THF)2 (x = 1, y = 3, z = 2 X = 2, y = 4, z s= 0) with two equivalents of MeLi,322 both complexes act as chemoselective reagents for alkene addition to a carbonyl compound. 328... 

The synthesis of a novel class of compounds, the 1,2-diacyl-l-cyano-alky 1-hydrazines, is depicted in Figure 7. The reaction of acid hydrazide with a carbonyl compound such as a ketone or an aldehyde, in the presence of aqueous sodium cyanide and one equivalent of hydrochloric acid, gave the l-cyanoalkyl-2-acyl hydrazine according to a general method described by T. R. Lynch, F. N. MacLachlan, and J. L. Suschitzky (IS). The subsequent acylation for the preparation of the final target molecules can be achieved by adding triethylamine into a mixture of l-cyanoalkyl-2-acylhydrazine and acyl chloride in the presence of 4-dimethylaminopyridine as a catalyst in dry methylene chloride. 

In the presence of a very strong base, such as an alkyllithium, sodium or potassium hydride, sodium or potassium amide, or LDA, 1,3-dicarbonyl compounds can be converted to their dianions by two sequential deprotonations.79 For example, reaction of benzoylacetone with sodium amide leads first to the enolate generated by deprotonation at the more acidic methylene group between the two carbonyl groups. A second equivalent of base deprotonates the benzyl methylene group to give a dienediolate. 

The prediction of product structure is difficult for such cycloadditions. The difficulty arises from the fact that either the ketene carbonyl group or olefinic linkage can act as the two-electron component. Indeed, in such cycloadditions, both modes of addition can be observed. When 3,3,4,4,5,5-hexamethyl-l,2-bis(methylene)cyclopentane 9 and diphenylke-tene were reacted in cyclohexane at 55 °C for long period of time, virtually equal amounts (70%) of dihydropyran 10 and the cyclohexenone 11 were obtained (Scheme 5). Compound 10 can be readily isomerized in acidic media to afford the conjugated diene 12. When the reaction of 1 with 9 was performed in benzonitrile instead of cyclohexane, the ratio of 10 11 rose from 1 1 to 3 1 (1987JCS(CC)1804). Interestingly, when the reaction was carried out in the presence of a Lewis acid such as ZnCla, two equivalents of diphenylketene was consumed which reacted with the diene to furnish a bicyclic lactone. 

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