Carbonyl substituted homolog

These have a partial common structure, i.e. enolyzed a-diketone and a-hydrogen to the enollzable carbonyl is substituted by a methyl group. For a characteristic sugary aroma, the presence of enol-hydrogen was essential, because the acetyl ester or methyl ether of sotolon showed no characteristic aroma. The extraordinarily low threshold value of sotolon may be due to its coexistence with hydrophilic and hydrophobic (alkyl-substituted lactone) partial structures in one molecule. The lower threshold value of the ethyl-substituted homolog (II) than that of sotolon may also be explained from the balance of these opposite physicochemical properties. 

The pyrrolidine phosphonate 125 does much the same thing in one step but the real virtue of these methods is that the enamines 123 and 126 are reactive enough to combine with various electrophiles, particularly allylic halides, a-halo-carbonyl compounds and Michael acceptors (see chapter 10) to give substituted homologous aldehydes or ketones28 127. 

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

MetaUation of 4-hetero-substituted dibenzothiins (427) with lithium, catalyzed by 4,4 -di-f-butylbiphenyl (equation 122), breaks one of the C—S bonds. Quenching with carbonyl compounds leads to the corresponding thiophenols (428) that may be cyclized to the homologous seven-membered heterocycles (429). The products can be characterized by IR, H and NMR spectroscopies and MS . ... 

Rhodium(II) acetate catalyzes C—H insertion, olefin addition, heteroatom-H insertion, and ylide formation of a-diazocarbonyls via a rhodium carbenoid species (144—147). Intramolecular cyclopentane formation via C—H insertion occurs with retention of stereochemistry (143). Chiral rhodium (TT) carboxamides catalyze enantioselective cyclopropanation and intramolecular C—N insertions of CC-diazoketones (148). Other reactions catalyzed by rhodium complexes include double-bond migration (140), hydrogenation of aromatic aldehydes and ketones to hydrocarbons (150), homologation of esters (151), carbonylation of formaldehyde (152) and amines (140), reductive carbonylation of dimethyl ether or methyl acetate to 1,1-diacetoxy ethane (153), decarbonylation of aldehydes (140), water gas shift reaction (69,154), C—C skeletal rearrangements (132,140), oxidation of olefins to ketones (155) and aldehydes (156), and oxidation of substituted anthracenes to anthraquinones (157). Rhodium-catalyzed hydrosilation of olefins, alkynes, carbonyls, alcohols, and imines is facile and may also be accomplished enantioselectively (140). Rhodium complexes are moderately active alkene and alkyne polymerization catalysts (140). In some cases polymer-supported versions of homogeneous rhodium catalysts have improved activity, compared to their homogenous counterparts. This is the case for the conversion of alkenes direcdy to alcohols under oxo conditions by rhodium—amine polymer catalysts... 

In the past, Darzens methodology was primarily used for the synthesis of aldehydes and ketones, as a homologation reaction without any consideration of stereocontrol in the epoxide formation. For this sequence, saponification of the a,P-epoxy ester followed by decarboxylation gives the substituted carbonyl compound ... 

A detailed study has been made of the reaction of nuclear substituted benzyl alcohols with synthesis gas in the presence of dicobalt octa-carbonyl (Wender, Greenfield, Metlin, and Orchin, 19). Under the conditions of the reaction it was postulated that some of the dicobalt octacarbonyl is converted to cobalt hydrocarbonyl, HCo(CO)4, which is a strong acid. It was of interest to determine the effect of different substituent groups on (a) the variations in the speed of the reaction and (b) the relative proportions of the hydrogenated and homologated product. All reactions were conducted in as nearly an identical fashion as possible. The results are shown in Tables II and III. 

The oxidative rearrangement of tertiary cyclopropylcarbinols to 3,4-unsaturated carbonyl compounds is analogous (or homologous) to the reaction of allylic alcohols, and is shown in the example in equation (29). This reaction has been shown to proceed stereospecifically in the conversion of the cis-substituted cyclopropylcarbinol (29) to the (Z)-enynone (30) shown in equation (30). The substrates with R = H, Me and TMS all gave comparable yields. 

By logical extension of the scheme one can generate substituted thiazoh-dine and its homologs by the reaction of appropriate carbonyl compounds with suitable Q -aminothiols (Scheme 2) [6]. 

In order to study possible side reactions which may reduce the yield in the Woodward method of annulation of azetidin-2-ones (Scheme 31) similar reactions of ylides (214), which do not contain groups capable of conversion to carbonyl by DMSO-acetic anhydride treatment, have been investigated. 30 A range of products, e.g. (215) and (216), were obtained. A mild, four-carbon homologation of the 4-formyl-substituted azetidinone (217) involving reaction with the phosphonium ylide (218) has been used to synthesize (219), a useful intermediate in the synthesis of carbacephem antibiotics. 3 ... 

Substituted benzyl alcohols can be converted with cobalt carbonyl to the homologous amides under mild conditions, even using sterically hindered secondary amines (equation 42). 

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