Synthesis of Functionalized Aldehydes and Ketones

Unsaturated Aldehydes and Ketones.—Successive treatment of silyloxycyclo-propanes with mercury(li) acetate and palladium(ii) chloride gives a-methylene ketones [equation (19)], and /3-trimethylsilylketones can be brominated and 

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Aldehydes and ketones could be asymmetrically a-amino-oxylated [36, 37] or a-aminated [38] to corresponding poly-functional compounds 8 and 9 by proline-catalyzed reactions with nitrosobenzene or diethyl azodicarboxylate in molten imidazoUum salts (Scheme 22.5). As compared to those in common solvents, the yields of a-aminoxylation products 8 of both aldehydes and ketones improved significantly in the IL medium and the enantioselectivity was excellent Yields and enantiomeric enrichment of hydrazino-aldehydes 9 were somewhat lower. The ionic environment considerably accelerated the processes and the (S)-proline/IL system could be quantitatively recovered after completion of the aminoxylation reaction and reused (5-6 times) without any loss of catalytic performance. Aldehyde-derived products 8 and 9 (R = H) could be reduced to chiral 1,2-diol derivatives 10 or configurationally stable heterocycles 11, which are valuable intermediates in asymmetric synthesis. 

Selective fluonnation in polar solvents has proved commercially successful in the synthesis of 5 fluorouracil and its pyrimidine relatives, an extensive subject that will be discussed in another section Selective fluonnation of enolates [47], enols [48], and silyl enol ethers [49] resulted in preparation of a/phn-fluoro ketones, fieto-diketones, heta-ketoesters, and aldehydes The reactions of fluorine with these functionalities is most probably an addition to the ene followed by elimination of fluonde ion or hydrogen fluoride rather than a simple substitution In a similar vein, selective fluonnation of pyridmes to give 2-fluoropyridines was shown to proceed through pyridine difluondes [50]... 

An ability to fonn caibon-caibon bonds is fundamental to organic synthesis. The addition of Grignaid reagents to aldehydes and ketones is one of the most frequently used reactions in synthetic organic chemistry. Not only does it pennit the extension of caibon chains, but because the product is an alcohol, a wide variety of subsequent functional group transformations is possible. 

Primary and secondary nitroalkanes, and substrates containing terminal em-dinitroaliphatic functionality, have one or more acidic a-protons, a consequence of inductive and resonance effects imposed by the nitro group. As a result, such compounds can behave like carbanions and participate in a number of addition and condensation reactions which are typical of substrates like ketones, aldehydes, and /S-ketoesters. Such reactions are extremely useful for the synthesis of functionalized polynitroaliphatic compounds which find potential use as explosives, energetic oligomers and plasticizers. 

Enantioselective -Functionalization of Aldehydes and Ketones The direct and enantiosective functionalization of enolates or enolate equivalents with carbon-, nitrogen-, oxygen-, sulfur- or halogen-centered electrophiles represents a powerful transformation of chemical synthesis and of fundamental importance to modem practitioners of asymmetric molecule constmction. Independent studies from List, J0rgensen, Cordova, Hayashi, and MacMiUan have demonstrated the power of enamine catalysis, developing catalytic enantioselective reactions such as... 

In addition, iodine snccessfnlly catalyzed the electrophilic snbstitntion reaction of indoles with aldehydes and ketones to bis(indonyl)methanes [225], the deprotection of aromatic acetates [226], esterifications [227], transesterifications [227], the chemoselective thioacetalization of carbon functions [228], the addition of mercaptans to a,P-nnsatnrated carboxylic acids [229], the imino-Diels-Alder reaction [230], the synthesis of iV-Boc protected amines [231], the preparation of alkynyl sngars from D-glycals [232], the preparation of methyl bisnlfate [233], and the synthesis of P-acetamido ketones from aromatic aldehydes, enolizable ketones or ketoesters and acetonitrile [234],... 

Removal of the amide function is much easier if the reaction is intramolecular, and —CONEt2 amides (sometimes even —CONPr-i2 amides) may be converted to lactones, lactams and other heterocycles in this way . Addition of an aldehyde or ketone as an electrophile generates a hydroxyl group (in some cases, atroposelectively, as it happens —though this is usually irrelevant to the stereochemistry of the product) which cyclizes to give a lactone via a benzylic cation in acid. This reaction has found wide use in the synthesis of polycyclic aromatics, particularly alkaloids. 

Acyclic acetals are simple protecting groups for aldehydes and ketones, and we have previously reported their synthesis catalyzed by Bi(OTf)3 [104]. Acyclic acetals can also be converted to other useful functional groups. For example, allylation of acyclic acetals to give homoallyl ethers has been well investigated, and we have reported a Bi(OTf)3-catalyzed method for the same [105]. The success of Bi(OTf)3-catalyzed formation and allylation of acyclic acetals prompted us to develop a one-pot method for the synthesis of homoallyl ethers from aldehydes, catalyzed by bismuth triflate. A one-pot process saves steps by eliminating the need for isolation of the intermediate and thus minimizes waste. Three one-pot procedures for the synthesis of homoallyl ethers were developed [106]. 

The oxidation of alcohols to the corresponding aldehydes, ketones or acids certainly represents one of the more important functional group transformations in organic synthesis and there are numerous methods reported in the literature (1-3). However, relatively few methods describe the selective oxidation of primary or secondary alcohols to the corresponding aldehydes and ketones and most of them traditionally use a stoichiometric terminal oxidant such as chromium oxide (4), dichromate (5), manganese oxide (6), and osmium or ruthenium oxides as primary oxidants (7). 

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