Acyclic Aliphatic Ketones

Cyclic and/or acyclic aliphatic ketones > C3 Secondary or tertiary aliphatic amines with 0-12 —... 

In the presence of 5 mol% CuBr SMe2 and 6mol% 17b, acyclic aliphatic enones can also react with Grignard reagents to provide / -substituted linear ketones in high yields (62-91%), good regioselectivities (>94 6), and excellent enantioselectivities (90-98%) (Scheme 10).24... 

The first asymmetric enamine-catalyzed Mannich reactions were described by List in 2000 [208]. Paralleling the development of the enamine-catalyzed aldol reactions, the first asymmetric Mannich reactions were catalyzed by proline, and a range of cyclic and acyclic aliphatic ketones were used as donors (Schemes 24 and 25). In contrast to the aldol reaction, however, most Mannich reactions are syn selective. This is presumably due to the larger size of the imine acceptor, forcing the imine and the enamine to approach each other in a different manner than is possible with aldehyde acceptors (Scheme 23). 

A semiempirical force field is constructed for the calculation of conformational potential energies of unstrained, acyclic, aliphatic aldehydes and ketones, taking solvent effects into consideration. Detailed conformational calculations for fitting and testing the necessary parameters are done. The results are incorporated into a RIS scheme for polylmethyl vinyl ketonels. 

All the enthalpies of formation for acyclic aliphatic aldehydes and ketones which are discussed in this section are tabulated by Pedley and coworkers16. The number of these carbonyl compounds whose enthalpies of formation have been measured are few compared to the abundant data available for alkenes and so there are fewer decisions to make on which data to include. However, we then lack the means to make the comprehensive analyses we would prefer. The demonstrated linearity34 of the enthalpies of formation of the members of a homologous series vs the number of carbon atoms, nc, in the molecules provides an excellent visual method for determining the quality of the data any enthalpy of formation which deviates significantly from linearity is of questionable reliability. The linear relationship can be expressed as in equation 4 and the results of the regression analyses of this equation for aldehydes and ketones appear in Table 4. 

CIDNP effects similar to those described here are found with other acyclic aliphatic ketones in benzene or n-hexane solutions They can be explained in terms of reactions like those of Scheme VII, 1. If CCI4 or other chlorinated solvents are applied, primary pair formation from singlet precursors seems possible... 

The regioselective Baeyer-Villiger oxidation of acyclic aliphatic ketones normally results in the insertion of oxygen next to the bulkier alkyl chain. Since methyl is a poor migrating group, a common use of this reaction is to reduce the chain length of methyl ketones 1 two carbons to provide alcohols, after hydrolysis. The ability to synthesize methyl ketones from acids and med l-sutetituted alkenes (equation... 

Reactions with Aldehydes and Ketones. The carbanion derived from the treatment of (Me0)2P(0)CH(SMe)2 with a base reacts with cyclic and acyclic, aliphatic and aromatic aldehydes and ketones in a Horner—Wadsworth—Emmons reaction to give ketene 5,5-thioacetals in high yields " (eq 2 ). The carbanion is generated using either butyllithium in THE at —78 °C > or, less commonly, sodium hydride in DME. Alternatively, with aromatic aldehydes the reaction may be performed under two-phase conditions using benzyltriethylammonium chloride (TEBA) as a phase-transfer catalyst. ... 

In the realm of secondary antino catalysis, acyclic aliphatic ketone donors have remained as challenging substrates in asymmetric Michael additions to nitrostyrene. Breakthroughs came with chiral primary amine-thioureas catalysts. Tsogoeva group [35] and Jacobsen group [36] have independently developed chiral primary antine-thiourea catalysts for the Michael reaction of acyclic ketones with nitrooleiins (Schemes 5.18 and 5.19). In both cases, good activity and enantioselectivity have been achieved in the reactions of acetones. Notably, anti-stereoselectivities were obtained in... 

The procedure described is an example of a more general synthetic method for the direct conversion of ketones into cyanides. " The reaction has been carried out successfully with acyclic and cyclic aliphatic ketones, including numerous steroidal ketones and aryl-alkyl ketones. The conversion of diaryl or highly hindered ketones such as camphor and )3,j8-dimethyl-a-tetralone requires the use of a more polar solvent. The dimethoxyethane used in the present procedure should be replaced by dimethyl sulfoxide. ... 

Organic-Base Catalyzed. Asymmetric direct aldol reactions have received considerable attention recently (Eq. 8.98).251 Direct asymmetric catalytic aldol reactions have been successfully performed using aldehydes and unmodified ketones together with chiral cyclic secondary amines as catalysts.252 L-proline and 5,5-dimethylthiazolidinium-4-carboxylate (DMTC) were found to be the most powerful amino acid catalysts for the reaction of both acyclic and cyclic ketones as aldol donors with aromatic and aliphatic aldehydes to afford the corresponding... 

In the Diels-Alder reaction with inverse electron demand, the overlap of the LUMO of the 1-oxa-l,3-butadiene with the HOMO of the dienophile is dominant. Since the electron-withdrawing group at the oxabutadiene at the 3-position lowers its LUMO dramatically, the cycloaddition as well as the condensation usually take place at room or slightly elevated temperature. There is actually no restriction for the aldehydes. Thus, aromatic, heteroaromatic, saturated aliphatic and unsaturated aliphatic aldehydes may be used. For example, a-oxocarbocylic esters or 1,2-dike-tones for instance have been employed as ketones. Furthermore, 1,3-dicarbonyl compounds cyclic and acyclic substances such as Meldmm s acid, barbituric acid and derivates, coumarins, any type of cycloalkane-1,3-dione, (1-ketoesters, and 1,3-diones as well as their phosphorus, nitrogen and sulfur analogues, can also be ap-... 

Twelve out of 15 ligands show good to excellent yields. The only unreactive one is the indanol amin ligand 54 with only 3% conversion. Regarding enantioselectivities the best results were obtained with the acyclic ligands 49 and 51. It was therefore decided to investigate aliphatic ketones. 

For example, Nakamura and Kuwajima [15] have described 1-alkoxy-l-trimethylsilyloxycyclopropanes (15) -prepared by reductive silylation of alkoxy 3-chloropropanoates-, which react with aliphatic aldehydes, but not with ketones, in the presence of one equivalent of TiCl4 to give good yields of y-lactones 17 through the acyclic derivative ethyl 4-hydroxybutanoate (16) (Scheme 5.10). With aromatic aldehydes and their acetals the reaction leads directly to acyclic 1,4-D derivatives. 

Reduction of aldehydes and ketones. Earlier work on amine borane reagents was conducted mainly with tertiary amines and led to the conclusion that these borane complexes reduced carbonyl compounds very slowly, at least under neutral conditions, and that the yield of alcohols is low. Actually complexes of borane with primary amines, NHj or (CH3)3CNH2, reduce carbonyl compounds rapidly and with utilization of the three hydride equivalents. BH3 NH3 is less subject to steric effects than traditional complex hydrides. A particular advantage is that NH3 BH3 and (CH3)3CNH2 BH3 reduce aldehyde groups much more rapidly than keto groups, but cyclohexanone can be reduced selectively in the presence of aliphatic and aromatic acyclic ketones. 

The overall course of reaction depends on the relative rate constants for the various secondary radical processes. Aliphatic ketones are often photoreduced to secondary alcohols (4.121, but although there are interesting features in the stereochemistry of the reduction, the method is not a worthwhile alternative to thermal reduction using hydride reagents, except in cases where the substrate is sensitive to basic conditions. Photoaddition of methanol is promoted in the presence of titaniurnfiv) chloride, both for acyclic and cyclic (4.33) ketones the titanium involvement probably starts in the early steps of the reaction, but the detailed mechanism is not known. Addition may also be a major pathway when cyclohexene is used as hydrogen source (4.341 unlike many other simple alkenes, cydohexene does not readily give oxetanes by photocycloaddition (see p. 126). 

Alcohol dehydrogenase-catalyzed reduction of ketones is a convenient method for the production of chiral alcohols. HLAD, the most thoroughly studied enzyme, has a broad substrate specificity and accommodates a variety of substrates (Table 11). It efficiently reduces all simple four- to nine-membered cyclic ketones and also symmetrical and racemic cis- and trans-decalindiones (167). Asymmetric reduction of aliphatic acyclic ketones (C-4-C-10) (103,104) can be efficiently achieved by alcohol dehydrogenase isolated from Thermoanaerobium brockii (TBADH) (168). The enzyme is remarkably stable at temperatures up to 85°C and exhibits high tolerance toward organic solvents. Alcohol dehydrogenases from horse liver and T. brockii... 

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