Ketones, preparation from carboxylic acid Lithium

Aldehydes and Ketones from Carboxylic Acids. Reduction of the derived acylimidazole (2) with Lithium Aluminum Hydride achieves conversion of an aliphatic or aromatic carboxylic acid to an aldehyde (eq 6). DiisobutyUduminum Hydride has also been used, allowing preparation of a-acylamino aldehydes fromiV-protected amino acids. Similarly, reaction of... 

A variety of carbanionic species derived from carboxylic acids, esters, amides, and nitriles have been prepared and added to aldehydes and ketones. Usually, strong bases such as lithium diisopropylamide are used owing to the low level of... 

The in situ generation of an afkyllithium reagent, from an alkyl chloride 13 and lithium in the presence of a catalytic amonnt of naphthalene (10%), and its reaction with carboxylic acids 14 allowed a general preparation of ketones 15 in a one-pot procednre (Scheme 6) °. 

Acylation. One of the most useful and important methods for preparations of alkylthiophenes is acylation. This is the reaction of carboxylic acids and carboxylic acid chlorides with thiophenes in the presence of a suitable catalyst and leads to 2-acylthiophenes in good yields (typically ca. 60-80% e.g. 23). Reduction of the ketone functionality by either a modified Wolff-Kishner procedure (8, 24) or with a mixed hydride, formed from aluminium trichloride and lithium aluminium hydride (25), yields the alkylthiophene (Figure 6). Alternatively, the ketone group can be alkylated, thereby giving access to 2-(r-alkyl)alkylthiophenes. 

As outlined in Scheme 28, the synthesis of the P-ketophosphonate 131 began with a one-pot anh -aldol/reduction step between ethyl ketone 101 and aldehyde 133, giving the 1,3-syn diol 134 (>30 ldr) [130, 132-136, 145, 146], The diol 134 was then converted into the carboxylic acid 135 in six steps. Completion of the subunit 131 required conversion into the acid chloride and reaction with the lithium anion of methyl-(di-l,l,l-trifluoroethyl)-phosphonate. The C9-C24 aldehyde 132 was prepared in two steps from 136, an intermediate from previous routes [55-58], The Still-Gennari-type coupling of 131 and 132 was readily achieved via treatment with... 

The a-chloro-a-sultinyl ketone 20 was prepared from methyl benzoate and chloromethyl phenyl sulfoxide 19 after in situ a-lithiation. Compound 20 is dimetallated by KH and f-BuLi to give the keto dianion 21, which is converted into a potassium/lithium ynolate 22 (equation 7). The resulting metal ynolates are converted into thioesters, carboxylic acids, amides and esters (Section V). 

O. R. XVIII-I, M. J. Jorgenson, Preparation of Ketones from the Reaction of Organo-lithium Reagents with Carboxylic Acids XVI, A. J. Nielsen and W. J. Houlihan, The Aldol Condensation IV-5, W. S. Ide and J. S. Buck, The Synthesis of Benzoins II-3, T. A. Geissman, The Cannizzaro Reaction V-6, N. N. Crounse, The Gattermann-Koch Reaction I-10, F. f. 3licke, The Mannich Reaction. ... 

Dilithium tetrachlorocuprate is recommended as an additive for cross coupling of Grignard compounds with tosylates even allylic and benzylic acetates give good yields . a-Methylene-ketones, -carboxylic acids and -lactones have been prepared via sulfides and sulfoxides. A convenient and general synthesis of acetylene derivatives from boranes via the reaction of iodine with lithium 1-alkynyltriorganoborates has been published ar-Nitrostyrenes can be easily obtained by a Wittig synthesis with formaldehyde in an aqueous medium . A new synthesis of unsym. ketones by reaction of dialkyldiloroboranes with lithium aldimines has recently been published . Metallo aldimines have also served for the synthesis of a variety of other compound classes such as a-hydroxyketones, a-keto acids, nitriles, and for the asym. synthesis of a-amino acids . Polycondensations of malononitriles with benzylic chlorides have been carried out quantitatively under mild conditions in dimethyl sulfoxide with triethylamine as acid acceptor . Carbonyl compounds can react with dibromoacetonitrile to yield a-bromo esters with additional carbon atom . ... 

In addition, ketones can be prepared from certain carboxylic acid derivatives, just as aldehydes can. Among the most useful reactions of this type is that between an acid chloride and a lithium diorganocopper reagent, R2CuLi. We ll discuss lithium diorganocopper reagents later in this chapter (Section 14.11) and will look at preparing ketones from acid chlorides in Section 16.4. 

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