Cycloketones

Another example of a cycHc product is the formation of cyclopentanone [120-92-3] as a thermal decomposition product in nylon-6,6 (81,82). The following mechanism (eqs. 8 and 9) accounts not only for the formation of the cycloketone but also for the increase in amine ends, the decrease in acid ends, and the evolution of CO2 that is observed in the thermal decomposition of nylon-6,6 (82). 

With strained cycloketones the type I-cleavage gives better yields, and can be used as a preparative method. For example photolysis of the bicyclic ketone 16 gives diene 17 in good yield ... 

When applied to a cycloketone, the Schmidt reaction leads to formation of a ring-expanded lactam—e.g. 14 15 ... 

In recent years the applicability of the Schmidt reaction for the synthesis of more complex molecules—especially the variant employing alkyl azides—has been further investigated. Cycloketones bearing an azidoalkyl side-chain at the a-carbon center have been shown to undergo, upon treatment with trifluoroacetic... 

Intermolecular Schmidt reactions of alkyl azides and hydroxyalkyl azides with cycloketones in the presence of a Lewis acid, lead to formation of iV-alkyl lactams and A-hydroxyalkyl lactams respectively in good yield. The synthesis of chiral lactams by an asymmetric Schmidt reaction has also been reported. ... 

Table 9.3 Desymmetrization of prochiral cycloketones to enantiocomplementaiy lactones by CHMO- (CHMO cmeto ind CHMOermi) and CPMO-type (CHMOerewZ and CPMOcoma) enzymes (representative examples).

Scheme 9.21 Kinetic resolution of racemic cycloketones by BVMOs.

Although a maj ority of research activities were dedicated to cycloketone converting BVMOs, the recently discovered novel MOs also enable stereoselective oxidation of noncyclic ketones to esters. An aliphatic open-chain monooxygenase (AOCMO) from Pseudomonas Jluorescens DSM 50106 displays stereoselective biooxidation of terminal acyl-groups in proximity to hydroxyls (Scheme 9.23). The biooxidation gives acetic... 

A related situation is found in the case of P-substituted cycloketones here, the electronic difference between the two a-carbons is almost insignificant, resulting in unselective migration upon chemical oxidation. BVMOs have a particularly different behavior, as they can influence the stereo- and/or regioselectivity of the biooxidation. In the latter case, the distribution of proximal and distal lactones is affected by directing the oxygen insertion process either into the bond close or remote to the position of the P-substituent. Consequently, a regioisomeric excess (re) can be defined for this biotransformation, similar to enantiomeric excess or diastereomeric excess values [143]. 

Similarly, Nakano et al. have prepared a number of alkylidenecycloke-tones by the oxidation of primary alcohols with cycloketones in the presence of Cp2ZrH2, which operates in a similar manner as aluminium alkoxides.60... 

The complex Et3N.5HF is an excellent electrolyte and functions as a convenient fluorine source for the partial fluorination of aliphatic aldehydes and cycloketones. It has now been found that electrolysis of cycloalkylideneacetates 1 with Et3N.5HF at -20°C results in smooth fluorinative ring expansion to give the difluorocycloalkyl esters 2 in moderate to good yield. 

I 21 Second Generation Boeyer-Villiger Biocatalysts Cycloketone converting BVMOs... 

This suite of cycloketone-converting BVMOs has recently been expanded for enzymes displaying appealing properties in the kinetic resolution of linear ketones. A BVMO from PseudomonasJluorescens turned out to be particularly useful for the conversion of terminal ketones to chiral diol derivatives [42, 69], while PAMO and HAPMO are suitable biocatalysts for the kinetic resolution of aromatic ketones and aldehydes [70]. 

Food Industry—As far as the compounds participating in food production are concerned, some investigations into the synthesis of food flavors are reported. Key steps of the process are represented by the preparation of cycloketones bearing methyls as ring substituents, carried out by hydrogenolysis of precursor aminomethyl derivatives. The Mannich synthesis is also applied to amino acid preparations for animal nutrition. ... 

Treatment of tosylhydrazones of tricyclic a-cycloketones with MeONa in MeOH at 40 °C or at room temperature gives moderate yields of cycloalkynones, occasionally intermixed with the corresponding allenes (e.g. equation 127) , ... 

So far, arylaldehydes have been the preferred substrates. Normal ketones are of little or no reactivity while strained cycloketones, particularly cyclobutanone, undergo olefination (eq. (4)). Within the series of benzaldehydes, electron-withdrawing substituents (e. g., P-NO2) favour the C-C coupling. 

Aldehydes or strained cycloketones, treated with aliphatic diazoalkanes in the presence of an equimolar amount of a tertiary phosphine and 1 as catalyst, afford an olefinic coupling product in good yields already at room temperature according to eq. (13) (cf. also Section 3.2.10) [2, 3, 25]. 

Liu et al. [79] further developed a Ru-catalyzed hydrogenation of racemic a,a -disubstituted cycloketones through DKR for the one-step synthesis of chiral diols with three contiguous stereocenters with high diastereoselectivity and enantioselectivity (Scheme 23). This new strategy facilitates the enantioselective total synthesis of alkaloid (-H)-y-lycorane. 

A one-pot synthesis of imidazolidines (30-67%) reacts aromatic aldehydes with diethyl keto-malonate and a benzylamine with a catalytic quantity of p-toluenesulfonic acid <94H(38)587>. The Ugi four-component eondensation of l,l-diethoxy-2-isocyanoethane, cycloketones, amine hydrochlorides, and potassium thiocyanate gives rise to 2-spiro-2W-imidazoles (10-48%) <93LAI229>. 

For the synthesis of the 24-epimer 41, expected also as a native brassinosteroid, the 3,5-cycloketone 48 was directly solvolyzed with aqueous H2SO4 to give the 3p-hydroxy-6-ketone... 

Condensed and other heterocyclic systems Nitrogen heterocycles. Condensed 3-cyanopyridines 236 were prepared from 179 and cycloketones 235 (n = 1,2, 3, 5). Ring... 

This efficient approach was successfully validated experimentally by Kaspereit and Sainio (2011) for two cycloketones with bi-Langmuir isotherms, as well as for an enantioseparations for a pharmaceutically relevant compound with complex quadratic isotherms (von Langermarm et al., 2012). 

Aldehyde olefination CHjReOs (1) is an efficient catalyst for condensation of aldehydes with a diazoalkane and a phosphine to form an alkene and a phosphine oxide. The actual catalyst may be CH3Re020PR3. The reaction is applicable to aliphatic and aromatic aldehydes and also to enals. Some cycloketones undergo this olefination but in only moderate yield. 

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