Enantioselective reactions continued ketones

Ulijn et al. identified an enzyme, capable of enantioselectively reducing the ketone, from their extensive collection of ADH variants further modification of the hit resulted in a biocatalyst that produces the desired (5)-alcohol in >99.9% ee at concentrations of 100 gL in a sofid-to-sofid biotransformation, where both starting material and product display only sparing solubility in the reaction medium. High conversions (>99%) are achieved by the substrate-coupled method, using 50 % v/v isopropyl alcohol concentrations to drive the reaction by continuous acetone removal (Scheme 1.55). The product can be easily isolated by filtration and washing. 

There are a number of different approaches to performing enantioselective reductions of ketones within the flow domain, using either a borane-derived hydride transfer agent such as that described previously or modified transition metal hydrogenations an example of the latter involved a column of Pt/Al203 modified with O-methyl cinchonidine (21) to induce chirality in the product (Scheme 4.64). Continuous monitoring showed that a 30 min induction period was required before the optimal reaction rate and ee could be obtained. This was ascribed to the need for... 

In total, over the past six years, the chelating P,N-ligands have shown considerable promise in a variety of enantioselective processes, including transfer-hydrogenation and hydrosilylation of ketones, hydroboration of alkenes, conjugate addition to enones and Lewis-acid catalysed Diels-Alder reactions, in addition to those described above.128,341 It is anticipated that this list will continue to grow, and... 

Hydroxyalkyt and Epoxyalky Acids. The reaction of aldehydes or ketones with dialkyl hydrogenphosphonate continues to be widely used for the synthesis of a-hydroxyalkylphosphonates ° and magnesium oxide has been reported to be an effective catalyst for the reaction. The reaction has been used in enantioselective synthesis. For example, in the preparation of chiral a, -dihydroxyphosphonic acids 171 and 172 (Scheme 14), with preferential formation of the jyn-isomer 171, and the statin analogue 2-amino-1-hydroxy-3-phenylpropylphosphonic acid (173) (Scheme 15). Catalytic asymmetric... 

The asymmetric catalytic reduction of ketones (R2C=0) and imines (R2C=NR) with certain organohydrosilanes and transition-metal catalysts is named hydrosilylation and has been recognized as a versatile method providing optically active secondary alcohols and primary or secondary amines (Scheme 1) [1]. In this decade, high enantioselectivity over 90% has been realized by several catalytic systems [2,3]. Therefore the hydrosilylation can achieve a sufficient level to be a preparative method for the asymmetric reduction of double bond substrates. In addition, the manipulative feasibility of the catalytic hydrosilylation has played a major role as a probe reaction of asymmetric catalysis, so that the potential of newly designed chiral ligands and catalysts can be continuously scrutinized. 

Reviews of general interest in this area highlights microreactors that can be used for a variety of photochemical reactions such as the synthesis of large ring ketones. Interest in the control that can be exercised on the outcome of photochemical reactions in constrained environments continues to increase and reviews dealing with the enantioselective photoreactions of achiral compounds in chiral crystals and inclusion crystals have been published. ... 

The chiral molecular receptor (35) has been used to effect enantioselective cyclization of the enone (36). The complex of (36) and (35) undergoes energy transfer from the ketonic acceptor to (36) and results in its conversion into the cyclobutanes (37) and (38) in a total yield of 21%. Bach et aV have continued their investigations of enantioselective additions mediated by the chiral lactam hosts (39). The present reactions involve intra and intermolecular additions of quinolone systems (40) at -60°C in toluene as solvent. The irradiation affords the cycloadducts (41) and (42). As can be seen, the ee of the products is high and the chemical yields are also good. An extension of the work to intermolecular reactions of the quinolone (43) was also reported. The additions of the alkenes... 

In continuation of synthetic study, Juaristi and coworkers investigated the efficacy of the series of (5 )-proline-thioamide catalysts C4-C6 (Chart 2.1) [35]. When aldol reaction of 3-nitrobenzaldehyde with cyclohexanone was carried out, the best results were obtained when using 7 mol % of catalyst C4. On the other hand, in ball-milling conditions at -20°C the use of water and acidic additives was beneficial for the increase of diastereoselectivity in favor of the anfi-diastereomer however, the enantiomeric excess of the process was not improved. Thus, reactions between cyelic ketones and aromatic were carried out in conditions identical to these in Table 2.35 to afford aldol products in good isolated yields (70-89%) with high diastereo- (92 8 to >98 2 anti/syn) and enantioselectivities (82-96% ee) (Table 2.37). 

Istuno and coworkers reported an enantioselective reduction ofketones using a flow reactor, in which polymer-supported amino alcohol was fixed (Scheme 7.7). As butyl phenyl ketone and borane (1.2 equiv.) in THF were separately and continuously pumped into the reactor (overflow type), the desired alcohol was obtained in 84% yield with 83-93% ee. With analogous batch reactions, ee values were 81%-92%. Thus, with this reaction, both the flow and batch procedures gave similar results [41]. 

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