Aldehydes, catalytic condensation with esters

Catalytic reduction of the nitrile 79 in the presence of semicarbazide affords initially the semicarbazone of 80. Hydrolysis-interchange, for example in the presence of pyruvic acid, gives the aldehyde 80. Condensation with the half ester of malonic acid leads to the acrylic ester 81 the double bond is then removed by means of catalytic reduction (82). Base catalyzed reaction of the... 

The aldol-type reaction of a cyclic enol ester, 5-methyl-2(3//)-furanone (4b), was carried out with three kinds of catalytic systems PdCl2 (PhCN)2-SnCl2, Ni(Cod)2/Ph3P-Zn, and Pd(OAc)2/PPh3-Zn. In the presence of the first catalyst, aromatic aldehydes condense with 4b to give ds-)3-acetyl-y-aryl-y-butyrolactones (47), but alkanals are mainly con-... 

Most C,H-acidic compounds can be condensed with aldehydes or ketones to yield alkenes. Some of these reactions have also been realized on insoluble supports, with either the C,H-acidic (nucleophilic) reactant or the electrophilic reactant linked to the support. Some illustrative examples are listed in Table 5.6. Polystyrene-bound malonic esters or amides, cyanoacetamides, nitroacetic ester [95], and 3-oxo esters undergo Knoevenagel condensation with aromatic or aliphatic aldehydes. Catalytic amounts of piperidine and heating are generally required, although reactive substrates can react at room temperature. 

This process represents a Knoevencigel condensation,3 a reaction in which a compound with an acidic methylene group, such as dimethyl malonate (8). condenses with a carbonyl compound like citronellal (9) to give an alkene. Reaction occurs in a weakly basic or neutral medium. Catalytic amounts of piperidinium acetate suffice to deprotonate malonic ester 8. The resulting anion 15 adds to the aldehyde citronellal (9) to give alkoxide 16. 

Diesters of malonic acid, as well as other active methylene compounds such as ace-toacetic esters and cyanoacetic esters, condense with aldehydes and ketones in the presence of catalytic amounts of primary or secondary amines or ammonium salts. 

The O-benzylated aldehyde 517 was also coiu erted into the a,p-unsaturated ester 522 through Wadsworth-Emmons reactioiT-- with ethyl 2-(diethoxyphosphono)acetate5 ° in excellent yield (Scheme 88). The intermediate alkene 522 was subjected to Sharpless asymmetric dihydroxylalion " to afford the diol ester 523 in excellent yield and with a diastereoselectivity in excess of 95 5. Subsequent to alkali-catalyzed hydrolysis of 523, the carboxylic acid obtained was condensed with the p-lolucncsulfonalc salt of glycine benzyl ester or phenylalanine benzyl ester, by the action of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC), to afford the benzyl-protected amide derivatives catalytic... 

With a bountiful supply of 69 at our disposal, the synthesis was continued by PCC oxidation to the aldehyde level and application of the Corey-Fuchs procedure [35] for chain homologation via dibromo olefin 70 to the acetylenic ester 71. Since amide bond construction next had to be implemented, this ester was saponified under mild conditions and the resulting carboxylic acid was activated by formation of a mixed anhydride with mesitylenesulfonyl chloride in advance of in situ condensation with 59. In order to preclude hydrolysis of the silyl ether functionality in 72, deacetalization had to be performed under anhydrous conditions in dry acetone containing a catalytic quantity of p-toluene-... 

Alkylphosphonate esters. The carbanion generated from dechlorination with BuLi condenses with aldehydes (and some ketones). Catalytic hydrogenation of the (chlorovinyl)phosphonate products affords phosphonates. 

The acid moiety of an amino acid can be activated for acyl substitution rather than converted to an aldehyde for acyl addition. Boc-alanine was converted to an acyl imidazole by reaction with carbonyl diimidazole (CDI see chapter two, section 2.4), and then condensed with the magnesium enolate of the mono ethyl ester of malonic acid to give keto-ester 5.9. Subsequent catalytic hydrogenation of the ketone moiety gave ethyl 3-hydroxy-5-(N-Boc amino)penlanoate, 5.10 Once the o... 

Reactions of Thiophen Aldehydes and Ketones.— The Stobbe condensation of some thienylcarbonyl compounds with dimethyl methylsuccinate in the presence of potassium t-butoxide or sodium hydride gave predominantly the ( -half esters of (156), while condensation with dimethyl homophthalate gave predominantly the (Z)-half ester of (157). Thiophen-2-aldehydes were shown to add smoothly to a -unsaturated ketones and nitriles, under the catalytic influence of cyanides, to form (158) and (159), respectively. Thiophen-2-aldehydes have been condensed with aliphatic amines and phenylenediamine to give Schiff bases ... 

Carboxylic esters can be treated with ketones to give p-diketones in a reaction that is essentially the same as 10-118. The reaction is so similar that it is sometimes also called the Claisen condensation, though this usage is unfortunate. A fairly strong base, such as sodium amide or sodium hydride, is required. Yields can be increased by the catalytic addition of crown ethers. Esters of formic acid (R H) give P-keto aldehydes. Ethyl carbonate gives P-keto esters. 

Early work on the asymmetric Darzens reaction involved the condensation of aromatic aldehydes with phenacyl halides in the presence of a catalytic amount of bovine serum albumin. The reaction gave the corresponding epoxyketone with up to 62% ee.67 Ohkata et al.68 reported the asymmetric Darzens reaction of symmetric and dissymmetric ketones with (-)-8-phenylmenthyl a-chloroacetate as examples of a reagent-controlled asymmetric reaction (Scheme 8-29). When this (-)-8-phenyl menthol derivative was employed as a chiral auxiliary, Darzens reactions of acetone, pentan-3-one, cyclopentanone, cyclohexanone, or benzophenone with 86 in the presence of t-BuOK provided dia-stereomers of (2J ,3J )-glycidic ester 87 with diastereoselectivity ranging from 77% to 96%. 

The other stereoselective synthesis/281 shown in Scheme 8, foresees conversion of Boc-L-Asp-OtBu 20 into the related (3-aldehyde 22 via the Weinreb amide 21 and its reduction with diisobutylaluminum hydride (DIBAL-H). Wittig condensation of 22 with the ylide derived from (3-carboxypropyl)triphenylphosphonium bromide using lithium hexamethyldisilaza-nide at —78 to 0°C, produces the unsaturated compound 23 which is catalytically hydrogenated to the protected L-a-aminosuberic acid derivative 24. Conversion of the co-carboxy group into the 9-fluorenylmethyl ester, followed by TFA treatment and reprotection of the M -amino group affords Boc-L-Asu(OFm)-OH (25). 

Heating the first-obtained product in a strong acid leads to the hydrolysis of the ester. The resulting (3-ketoacid loses carbon dioxide under reaction conditions the acetal hydrolyses also reveal the free aldehyde (106-6). Aldol condensation of this last intermediate in the presence of a base with readily available rhodanine (106-7) links the two fragments. The double bond in the first-formed product is then reduced catalytically to afford darglitazone (106-8) [117]. 

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