Ketone hydrogenation substrates

The catalysts were obtained from their respective commercial sources and for some of these tests they were subjected to RPT by heating them to 400°C for 2 hours under a flow of hydrogen. The enantioselective ketone hydrogenations were carried out in a 50 ml stainless steel autoclave stirred with a magnetic stirring bar with 10 to 30 mg of catalyst, 10 to 30 mg of MeOHCd, 5 ml substrate and 20 ml AcOH at 60 bar and 25°C for 30 minutes. The crotonic acid hydrogenations were carried out in an ethanolic solution at atmospheric pressure and room temperature stirred at 2000 rpm with a hollow shaft bubbling stirrer. 

The Meerwein-Ponndorf-Verley reaction is a classic method for ketone/ aldehyde carbonyl group reduction, which involves at least 1 equivalent of aluminum alkoxide as a promoter. In this reaction, the hydrogen is transferred from isopropanol to the ketone/aldehyde substrate, so the reaction can also be referred to as a transfer hydrogenation reaction. 

Hydrogenation of aldehydes and ketones Hydrogenation of miscellaneous organic substrates... 

A deep study of the 4-tert-butylcyclohexanone reduction aimed at understanding the effect of the donor alcohol structure revealed the existence of a two-step mechanism based on donor alcohol dehydrogenation and ketone hydrogenation. In particular, when the reaction was carried out in the presence of Cu/Si02, in order to exclude a contribution from the support, all the alcohols used as donors were capable of transferring H2, and in the case of (iPr)2CHOH and 3-octanol, not only was the formation of the corresponding ketone observed but it continued after complete conversion of the substrate. 

The ammoximation of cyclohexanone had been known before the discovery of TS-1, but the performances of conventional catalysts were far below the standards required for development work. In the EniChem process, the reaction is carried out in the liquid phase, at ca. 80°C, using a suspension of TS-1 in aqueous t-butanol, with a slight excess of hydrogen peroxide over the ketone. The substrate and the oxidant undergo total conversion with selectivities close to 98% and 94%, respectively. Inorganic by-products comprise minor amounts of ammonium nitrate and nitrite, N2O, and N2 produced by the oxidation of ammonia, and O2 by the decomposition of the oxidant. 

Rhodium-chiraphos cations also hydrogenate ketone and epoxide functionalities, albeit with low optical yields, and are, therefore, not synthetically useful. While this rhodium system seems somewhat limited to the preparation of amino acids, other rhodium and ruthenium catalyst precursors are currently available which show enhanced activity and selectivity for a much broader group of hydrogenation substrates. 

Daley, C. J. A., Bergens, S. H. The Eirst Complete Identification of a Diastereomeric Catalyst-Substrate (Alkoxide) Species in an Enantloselectlve Ketone Hydrogenation. Mechanistic Investigations. J. Am. Chem. Soc. 2002,124, 3680-3691. 

Ruthenium and rhodium complexes have maintained the best track record as ketone hydrogenation catalysts. For high enantioselectivities, additional chelating functional groups are often needed. Typical substrates are represented by ketones (3.01) to (3.03), where esters, halides and phosphonates provide an additional donor group on the substrate. BlNAP/ruthenium combinations, such as complex (3.07), have given consistently high enantioselectivities with such... 

Hydrosilylation reactions are formal additions of Si-H units across multiple bonds. They are fundamental reactions in organosilicon chemistry. Despite early reports of Marinetti and Ricard on Pd-catalysed hydrosilylation of alkenes with phosphetanes (up to 65% ee with styrene) and of Zhang and co-workers on Ru-catalysed hydrosilylation of ketones (up to 54% ee with acetophenone), most of the work on enantioselective hydrosilylation with P-stereogenic ligands has been carried out with Rh(I) complexes and prochiral ketones as substrates. Initially, silyl ethers are formed but they are usually cleaved under acidic conditions affording alcohols. As a result, hydrosilylations of ketones are formally identical to hydrogenations but do not involve the manipulation of dihydrogen. The model substrate for enantioselective hydrosilylation is acetophenone (Scheme 7.17). 

A catalytic amount of Sc(OTf)3 was found to promote the reaction of less reactive N-acylhydrazones (aromatic aldehyde- or ketone-derived substrates) with trimethylsilylcyanide (TMSCN) to give a-hydrazinonitriles in the presence of an amine (Scheme 12.10) [18]. A mechanistic study indicated that the amine worked as a Bronsted base, which initiated the reaction by abstraction of the amide hydrogen of the substrate. Sc(OTf)3 might act as a Lewis acid to activate the stable intermediate O-Si-(l). This is a rare example of cyanation of C=N bonds promoted by a Bronsted base and a Lewis acid. 

Deuteriums in the enolizable positions of a,/3-unsaturated keto substrates are unaffected during the course of the reduction. This extends the applicability of this procedure to the preparation of y-labeled ketones by subjecting the substrates to hydrogen-deuterium exchange (section ll-C) prior to reduction. This technique has been utilized for the preparation of the y-labeled ketones (156), (157) and (158). " The deuteriums in the a-positions of these ketones are back exchanged (section 11-B) after the reduction. 

With ketones bearing a -hydrogens, a halogenation at that position is a possible side-reaction, and may lead to cleavage of the substrate. ... 

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