Acetone aromatic aldehydes

A different type of catalysis is observed using proline as a catalyst.166 Proline promotes addition of acetone to aromatic aldehydes with 65-77% enantioselectivity. It has been suggested that the carboxylic acid functions as an intramolecular proton donor and promotes reaction through an enamine intermediate. 

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%. 

Other related reactions involve TV-fluorenylmethyloxycarbonyl (N-Fmoc) AAs and aliphatic aldehydes (83JOC77) or substituted /-butoxycarbonyl (N-Boc) Aas and 2,2-dimethyoxypropane (acetone dimethyl ketal) (84TL5855 87JOC2361 88TL2019), as well as A-(dimethylthio)methylene derivatives of an AA and aromatic aldehydes [89JCS(P1)1577]. 

The methoxy derivatives may be treated directly o-methoxyphenyl-acetone, heated with hydrobroniic acid in acetic acid, gives 2-methyl-benzofuran.326 o-Methoxylated phenylacetones are readily prepared by glycidic synthesis from o-methoxylated aromatic aldehydes the intermediate glycidic ester (127) can be directly converted by pyridine hydrochloride into a 2-alkylbenzofuran in 40-80% yield.105... 

This procedure is quite general for other aromatic aldehydes. An excess of bisulfite must be avoided in the washing step, since many phenyl-substituted acetones react appreciably with it. 

Aromatic aldehydes. Acetone cyanohydrin can be used in place of hydrogen cyanide in the Gattermann reaction for formylation of arenes.1 Example ... 

Several prolinamides have been examined (38) catalyses the reactions of acetone with both aliphatic and aromatic aldehydes with ees up to 97%.104 It is proposed that amide and alcohol groups simultaneously donate hydrogen bonds to the aldehyde, while the gem-diphenyl moiety s bulk orients the aldehyde s approach. 

A study by Hayashi et al. demonstrates that less reactive electron-rich aromatic aldehydes efficiently undergo Mannich reactions under high pressure induced by water freezing [8], For instance, in the Mannich reaction of p-anisaldehyde, 3,4-dimethoxybenzaldehyde or N-acetyl-(4-formyl)aniline, with acetone and p-anisidine, good yields (61-99%) and excellent enantioselectivities (92-97%) have been obtained under water-freezing high-pressure conditions while there is no reaction at room temperature at 0.1 MPa (Scheme 9.6). 

Aromatic aldehydes condense well with aliphatic ketones such as acetone to give either the mono- 31 or di-adducts 29 depending on conditions.4 In an excess of acetone, 31 is the main... 

For satisfactory diemo- and stereoselectivity, most catalytic, direct cross-aldol methods are limited to the use of non enolizable (aromatic, a-tert-alkyl) or kineti-cally non enolizable (highly branched, ,/funsaturated) aldehydes as acceptor carbonyls. With aromatic aldehydes, however, enantioselectivity is sometimes moderate, and the dehydration side-product may be important. With regard to the donor counterpart, the best suited pronucleophile substrates for these reactions are symmetric ketones (acetone) and ketones with only one site amenable for enolization (acetophenones). With symmetric cyclic or acyclic ketones superior to acetone, syn/anti mixtures of variable composition are obtained [8b, 11, 19a]. Of particularly broad scope is the reaction of N-propionylthiazolidinethiones with aldehydes, which regularly gives high enantioselectivity of the syn aldol adduct of aromatic, a,fi-unsaturated, branched, and unbranched aldehydes [13]. 

Diamines grafted on MCM-41 revealed higher base catalytic activity because they were able to catalyse condensation between benzaldehyde and ethyl malonate which is usually less active than ethyl cyanoacetate. The catalytic activity was also high with less reactive carbonyl derivatives, such as cyclic or aliphatic ketones. Moreover, aldolization between acetone and aromatic aldehyde was also possible.11721... 

Esters of 3-aryl-4,5-dihydroisothiazole-4- and -5-carboxylic acids are unstable and aromatize in acetone solution (78JOC3742). The 1-methyl 1-oxide compound (157) is converted into 1,2-benzisothiazole on heating at 155 °C (80MI41700). 1-Methyl-3H-2,1-benzisothiazole 2,2-dioxide (158) loses sulfur dioxide on pyrolysis to give compound (159) (80CC471), and condenses with aromatic aldehydes to give compounds (160 Scheme 25) <75SST(3)54l). 

Not only does acetone undergo a highly enantioselective aldol reaction, but hydroxy acetone exhibits excellent stereoselectivity to produce the anti-aldol products 75 (Scheme 2.3d). For example, L-proline catalyzed the aldol reaction between hydroxy acetone and cyclohexanecarbaldehyde to furnish the anti -diol in 60% yield with a greater than 20 1 diastereomeric ratio. The enantiofacial selectivity of the anti-isomer was higher than >99%. Diastereoselectivities are very high with a-substituted aldehydes, whereas low selectivities are recorded in reactions with aromatic aldehydes and with a-unsubstituted aliphatic aldehydes. It is noteworthy that the levels of enantiofacial selectivity for the anti -aldol products... 

Now for a surprising product, whose structure and stereochemistry can be determined by NMR. Normally, reaction of a symmetrical ketone such as acetone with an aromatic aldehyde and base gives a double aldol condensation product in good yield. 

The crossed condensation of an aromatic aldehyde with a ketone usually gives a high yield of the unsaturated ketone directly. Acetone is condensed with either one or two molecules of benzaldehyde to give ben-zalacetone (68%) or dibenzalacetone (94%), respectively. Alkyl stytyl ketones, CjHs CH = C(R)COR, have been prepared from benzalde-hyde and higher ketones in the presence of hydrochloric acid or alkali hydroxide. Substituents on the phenyl group include methyl, hydroxyl, methoxyl, and nitro groups. A survey of condensa-... 

Kinetic studies have revealed that aliphatic ketyl radical anions are very shortlived compared with aromatic (half life of acetone " in aqueous 2-propanol is 72 ps, whereas that for acetophenone " is 1.5 ms) [253]. The reductive dimerization of simple aromatic aldehydes has been studied in aprotic solvents, with the second order rate constant being larger in acetonitrile than in DMF, because of ion-pair effects [254]. Electron-withdrawing substituents reduce the speed of dimerization (benzaldehyde " k = 2.4x 10 m" s", p-cyanobenzaldehyde k = 5 M s" ) [255], whereas protic solvents lead to protonation before dimerization [256]. 

In the presence of anhydrous copper sulfate, aliphatic oxiranes react stereoselect-ively with acetone, but (E)- and (Z)-aryl-aliphatic oxiranes give the same isomer mixture. A study has been made of the kinetics of formation of dioxolanes from oxiranes and aromatic aldehydes in a neutral medium. Dioxolane and dioxan isomers are obtained from the reaction of 2,3-epoxybutane and carbonyl compounds. ... 

Aldol condensations at one or both a-methylene groups of 3-thietanone have been accomplished with formaldehyde, aromatic aldehydes (e-g-, the formation of 359), acetylenic aldehydes, and acetone. ... 

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