Ketenes, preparation from ketones

This Asian species is a major agricultural pest. The pheromone has been proposed to consist of three male-specific compounds, only one of which, (Z)-exo-a-bergamotenal 150, has been reported in the literature [114]. The racemic compound was synthesized starting from farnesoic acid chloride 146 (Scheme 25) [114]. Thus, the vinyl ketene prepared from acid chloride 146 underwent 2+2 cycloaddition to give bicyclic ketone 147. The ketone function was removed by reaction with hydrazine followed by treatment of the resulting hy-... 

This catalytic enamine formation is limited to aldehydes and ketones as starting materials - it does not appear to be possible to prepare corresponding enamines , i.e. A,0-ketene acetals, from esters in this fashion. Nevertheless, the preparation of simple, reactive nucleophiles from normally electrophilic species, aldehydes and ketones, in a catalytic fashion sounds highly attfactive. Furthermore, the catalytic nature of these reactions allows the use of chiral amines, and the further possibility that these reactions can be rendered enantioselective. Enamines react readily with a wide variety of electrophiles, and the range of reactions that can be catalyzed by enamine catalysis is summarized in Scheme 2. 

Macrocyclic 2-pyrones (113) and (114) are prepared from enamine (115) and ketene (75HCA2409). Reduction of cyano ketone (116) with LAH affords an amino ketone which spontaneously cyclizes to generate a tetrahydropyridine (117) dehydrogenation by palladium on charcoal produces the aromatized phane (118) (71TL671). 

Alcohols can also be prepared from support-bound carbon nucleophiles and carbonyl compounds (Table 7.4). Few examples have been reported of the a-alkylation of resin-bound esters with aldehydes or ketones. This reaction is complicated by the thermal instability of some ester enolates, which can undergo elimination of alkoxide to yield ketenes. Traces of water or alcohols can, furthermore, lead to saponification or transesterification and release of the substrate into solution. Less prone to base-induced cleavage are support-bound imides (Entry 2, Table 7.4 see also Entry 3, Table 13.8 [42]). Alternatively, support-bound thiol esters can be converted into stable silyl ketene acetals, which react with aldehydes under Lewis-acid catalysis (Entries 3 and 4, Table 7.4). 

Cu(II) and Sn(II) Bisoxazolinc Complexes. Evans has prepared and studied a family of Cu(II) complexes prepared from bisoxazoline ligands [8]. Utilizing these complexes a number of different addition reactions can be successfully conducted on pyruvate, benzyloxyacetalde-hyde, and glyoxylates. Whereas the focus of the work in the context of aldol addition reactions has been on the use of silyl ketene acetals (vide infra), the addition of ketone-derived enoxy silanes 8a-b with methyl pyruvate has been examined (Eq. 8B2.1). The additions of 8a-b proceed in the presence of 10 mol % Cu(II) catalyst at -78°C in CH2Cl2, affording adducts of acetophenone 9a and acetone 9b with 99% and 93% ee, respectively. 

Mixed ketene 0,5-acetal derivatives (157) can be readily prepared from the reaction of [methoxy(phe-nylthio)(trimethylsilyl)methyl]lithium, generated from the mixed acetal (158), with aldehydes and ketones (Scheme 70). 

An interesting route to a-carboxy-8-lactones (81) and a-methylenelactones (80), based on hydrolysis of Knoevenagel products (79) of Meldrum s acid with cyclic aliphatic ketones (78), has been developed (Scheme 14). Reduction of 5-methylene derivatives of Meldrum s acid has been performed catalyti-caiiyi30 or by use of LAH. Imidoylation reaction of Meldrum s acid and subsequent solvolysis of the resulting (82) yields -enamino esters (83) in good yields.Flash vacuum pyrolysis of alkylidene derivatives of Meldrum s acid can be used to prepare methylene ketenes (84), a class of compounds difficult to prepare by conventional methods. By this procedure, methylene ketenes are obtained from aromatic aldehydes and ketones and from aliphatic ketones in only two steps. Intramolecular trapping of the methylene ketene obtained from the ketone (85) has been used successfully in the synthesis of the naphthol (86). ... 

Aldol and imino-aldol reactions. A Yb complex prepared from YbfOTflj and a C -symmetric a,a -bistriflamidobibenzyl has been used in the Mukaiyama aldol reaction," resulting in moderate asymmetric induction. Imines are activated toward enol derivatives, such as ketene silyl ethers. iV-(a-aminoalkyl)benzotriazoles are suitable surrogates of imines. One-pot syntheses of p-amino esters and ketones can also be achieved. 

The role of stoichiometric amount of zinc compounds in the aldol reaction was studied 30 years ago (107). The first study of asymmetric zinc-catalyzed aldol reaction was carried out by Mukaiyama and co-workers the chiral zinc catalyst was prepared from diethylzinc and chiral sulfonamides and was effective in the reaction of ketene silyl ethers with aldehydes (108). Among the subsequent studies on zinc-catalyzed aldol reactions, Trost s group gave important contribution to zinc/prophenol ligand complexes (109,110). The chiral dinuclear zinc catalyst promotes the direct aldol reaction of ketones, including a-hydroxyketones, and aldehydes with excellent enantioselectivity (Scheme 17). It is proposed that one zinc metal coordinated different substrates to form zinc enolate, and another zinc metal center provided the bridge between the interaction of donor and acceptor. 

Hydroxyorthothioesters, e.g. (66), which can be prepared from orthothioesters and aldehydes or ketones, are transformed into keten thioacetals, e.g. (67), on treatment with P2I4 and triethylamine. /3-Hydroxythioacetals furnish vinyl sulphides under the same conditions, and the method works equally well with the selenium analogues. The ylide generated from the stable phosphonium salt (68) is a convenient reagent for the transformation of aliphatic or aromatic aldehydes (but not ketones) into keten dithioacetals. ... 

Aminoalkenes (72) are readily prepared from dimethylaminopropyl chloride, magnesium, and the corresponding ketones (R R CO) in a one-pot procedure which is reported to result in higher yields than those obtained by a stepwise method. Another one-pot method involves the reaction between an alkyl halide (R R CHX), magnesium, and CS2 followed by LDA-R X to yield keten-thioacetals (73). ... 

Furthermore, ketene dithioacetals 83 prepared from unsaturated ketones 82 by means of Peterson reactions are converted to the bicydic lactones 84 by treatment with cerium(IV) ammonium nitrate (CAN) in wet acetonitrile (Scheme 2.51) [142]. The oxidative cydization occurs stereosdectively in moderate yields. 

KETENE, feef-butylcyano-, 55, 32 37, 38 Ketene 1 1-dimethylpropylcyano-, 55, 38 7-KETOESTERS, 58, 79, 81, 82 7-KETOESTERS TO PREPARE CYCLIC DIKETONES, 58, 83 KETONE terf-butyl phenyl, 55, 122 Ketone, methyl ethyl- 55, 25 Ketone, methyl vinyl, 56, 36 KETONES, acetylenic, 55, 52 Ketones, alkylation of, 56, 52 KETONFS aromatic, aromatic hydrocarbons from 55, 7... 

Recently, Mukaiyama and co-workers prepared cinchona alkaloid-derived chiral quaternary ammonium phenoxide-phenol complex 23 and used it as an efficient organocatalyst for the tandem Michael addition and lactonization between oc,f-unsaturated ketones and a ketene silyl acetal 24 derived from phenyl isobutyrate. This approach permits the highly enantioselective synthesis of a series of 3,4-dihydropyran-2-ones (25), as shown in Scheme 4.11 [17]. 

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