Cyclohexanones selective reduction

Modified Wolff-Kishner methods work well on ordinary cyclobutanones. Generally, the hydrazones are made at fairly mild reaction temperatures, base is added and the cyclobutane is distilled directly from the hot reaction mixture.237,272 279-284 The hydrazone can also be isolated prior to the reduction.285 The relatively facile reduction of cyclobutanones which occurs before that of larger ring ketones can be utilized in the selective reduction of cyclobutanones in the presence of, for example, a cyclohexanone, i.e. pentaspiro[3.1.3.3.3.3]heneicosane-5,11,19-trione was reduced in a stepwise manner to pentaspiro[3.1.3.3.3.3]heneicosane-5-one.237... 

Especially worth mentioning in a green context is the use of mesoporous materials and zeolites, as stable and recyclable catalysts for MPV reductions. High activity was obtained by using zeolite-beta catalysts. Beta zeolites have a large pore three-dimensional structure with pores of size 7.6 x 6.4 A2 which makes them suitable for a large range of substrates. Al, Ti- and Sn-beta zeolite have all been used as catalysts for the selective reduction of cyclohexanones [40-42]. The... 

Ethereal solvents, principally THF, either with or without sonication, have been reported to give results similar to those obtained on reductions in NH3 with no added proton donor, and pinacol formation as a major reaction path. a potentially useful selective reduction of unhindered cyclohexanones in the presence of other ketones using A1 amalgam in aqueous THF has been described and will be discussed in detail subsequently (Section 1.4.3.3.2).2 in this procedure aliphatic ketones give no pinacols however, aromatic ketones give only the corresponding pinacol.2 ... 

Organic fluorine compounds and methods for their preparation are the central topic of the next four procedures. Much of the synthetic versatility of methyl phenyl sulfone is embodied in FLUOROMETHYL PHENYL SULFONE and the fluoro Pummerer reaction of methyl phenyl sulfoxide with DAST is a key step in its preparation. The utility of this fluoromethyl sulfone in the preparation of fluoroalkenes Is demonstrated in a companion procedure for Z-[2-(FLUOROMETHYLENE) CYCLOHEXYL]BENZENE, a procedure with several prominent stereoselective features. Geminal difluoroalkenes are featured in the following procedure. (3,3 DIFLUOROALLYL)TRIMETHYLSILANE is prepared by a method in which the radical addition of dibromodifluoromethane to alkenes and the selective reduction of a-bromoalkylsilanes are key steps. A procedure for nucleophilic introduction of the trifluoromethyl group completes this set. The key reagent, (TRIFLUOROMETHYL)-TRIMETHYLSILANE is obtained by reductive coupling of TMS chloride and bromotrifluoromethane. Liberation of a CF3- equivalent with fluoride ion in the presence of cyclohexanone affords 1-TRIFLUOROMETHYL-1-CYCLOHEXANOL. 

Attempted intermolecular coupling of ketones and nitriles under conditions similar to those used for intramolecular coupling led to mixtures of two types of ketone-nitrile coupling products and alcohols resulting from ketone electroreduction. Product selectivity could be changed altering nitrile/solvent (2-propanol or ethanol) composition. Some results for cyclohexanone/acetonitrile reductions are shown in Scheme 27. 

The tetrahydro-l,3-oxazine (132) from cyclohexanone and aminopro-panol was converted to the diazo-intermediate (133) and cyclised using rhodium acetate to the tra i-P-lactam (134). Non-selective reduction of the ketone gave both hydroxy epimers. Progression through the sequence as outlined provided the thiol-ester phosphorane (138) possessing the required ( )-acetamidoethenyl substituent. Cyclisation in boiling toluene gave the two epimers of (139) which were separated, and deprotected to afford (+)-MM 22383 (140) and ( )-iV-acetyldehydrothienamycin (141). 

Dicyclohexylarnine may be selectively generated by reductive alkylation of cyclohexylamine by cyclohexanone (15). Stated batch reaction conditions are specifically 0.05—2.0% Pd or Pt catalyst, which is reusable, pressures of 400—700 kPa (55—100 psi), and temperatures of 75—100°C to give complete reduction in 4 h. Continuous vapor-phase amination selective to dicyclohexylarnine is claimed for cyclohexanone (16) or mixed cyclohexanone plus cyclohexanol (17) feeds. Conditions are 5—15 s contact time of <1 1 ammonia ketone, - 3 1 hydrogen ketone at 260°C over nickel on kieselguhr. With mixed feed the preferred conditions over a mixed copper chromite plus nickel catalyst are 18-s contact time at 250 °C with ammonia alkyl = 0.6 1 and hydrogen alkyl = 1 1. 

Fukui [51] predicted the deformation of the LUMO of cyclohexanone by the orbital mixing rule [1,2] and explained the origin of the % facial selectivity of the reduction of cyclohexanone. Tomoda and Senju [52] calculated the LUMO densities on the... 

For reduction of monofunctional ketones, the most effective catalysts include diamine ligands. The diamine catalysts exhibit strong selectivity for carbonyl groups over carbon-carbon double and triple bonds. These catalysts have a preference for equatorial approach in the reduction of cyclohexanones and for steric approach control in the reduction of acyclic ketones.51... 

We recently reported that Cu/Si02 is an effective catalyst for the hydrogenation of cyclohexanones under very mild experimental conditions. Thus, a series of cyclohexanones with different substituents, including 3-oxo-steroids, could be reduced under 1 atm of H2 at 40-90°C, with excellent selectivity (5). The catalyst is non-toxic and reusable. This prompted us to investigate the reduction of cyclohexanones over a series of supported copper catalysts under hydrogen transfer (h.t.) conditions (2-propanol, N2, 83 °C) and to compare the results with those obtained under catalytic hydrogenation (n-heptane, 1 atm H2, 40-90°C) conditions. Here we report the results obtained in the hydrogenation of 4-tert-butyl-cyclohexanone, a molecule whose reduction,... 

The first example of this type of transformation was reported in 1974 [76]. Three catalysts were investigated, namely [Co2(CO)8], [Co(CO)g/PBu ], and [Rh6(CO)i6]. The [Co OJg/PBu ] catalyst showed activity for reductive animation using ammonia and aromatic amines. The [Rh6(CO)16] catalyst could be used for reductive animation using the more basic aliphatic amines that were found to poison the cobalt catalyst. This early report pointed out that the successful reductive animation of iso-butanal (Me2CCHO) with piperidine involves selective enamine hydrogenation, that reductive animation of cyclohexanone with isopropylamine probably involves imine hydrogenation, and that reductive amination of benzaldehyde with piperidine would presumably involve the reduction of a carbinolamine. 

Several reagents reduce aldehydes preferentially to ketones in mixtures of both. Very high selectivity was found in reductions using dehydrated aluminum oxide soaked with isopropyl alcohol and especially diisopropylcarbinol [755], or silica gel and tributylstamane [756]. The best selectivity was achieved with lithium trialkoxyalumimm hydrides at —78°. In the system hexanal/ cyclohexanone the ratio of primary to secondary alcohol was 87 13 at 0° and 91.5 8.5 at —78° with lithium tris(/er/-butoxy)aluminum hydride [752], and 93.6 6.4 at 0° and 99.6 0.4 at —78° with lithium tris(3-ethyl-3-pentyl-oxy)aluminum hydride [752],... 

A Although it would be possible to convert 3-bromo-4-melhylani-line (7.2) into the corresponding hydrazine, by diazotization and reduction, react it with cyclohexanone, and then subject the product hydrazone to a Fischer indolization, the bromine substituent would still remain in the indole (note two isomers would form). Of course, this substituent could be displaced reductively using tributyltin hydride and a radical initiator [AIBN, azobis(isobuty-ronitrile)], but the overall synthesis is clumsy and non-selective and there should be a simpler route. 

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