Aryl/alkyl ketones transfer hydrogenation

Table 4.9 Asymmetric transfer hydrogenation of aryl alkyl ketones in Pr0H/H20, catalyzed by 93a,b and 94a,b. ...

Sinou and coworkers evaluated a range of enantiopure amino alcohols derived from tartaric acid for the ATH reduction of prochiral ketones. Various (2R,iR)-i-amino- and (alkylamino)-l,4-bis(benzyloxy)butan-2-ol were obtained from readily available (-I-)-diethyl tartrate. These enantiopure amino alcohols have been used with Ru(p-cymene)Cl2 or Ir(l) precursors as ligands in the hydrogen transfer reduction of various aryl alkyl ketones ee-values of up to 80% have been obtained using the ruthenium complex [93]. Using (2R,3R)-3-amino-l,4-bis(benzyloxy)butan-2-ol and (2R,3R)-3-(benzylamino)-l,4-bis(benzyloxy)butan-2-ol with [lr(cod)Cl]2 as precursor, the ATH of acetophenone resulted in a maximum yield of 72%, 30% ee, 3h, 25 °C in PrOH/KOH with the former, and 88% yield, 28% ee, 120 h with the latter. 

Scheme 9 Transfer hydrogenation of aryl(alkyl)ketones catalyzed by 7...

Other Applications. In the reactions discussed so far, methylenebis(oxazolines) were found to be superior to bioxazo-lines of type (4). However, there are some enantioselective metal-catalyzed processes for which the bioxazolines (4) are better suited than neutral or anionic methylenebis(oxazolines). Two examples, the Ir-catalyzed transfer hydrogenation of aryl alkyl ketones and the Rh-catalyzed hydrosilylation of acetophenone, are given in eq 10 and eq 11. 

An approach to aflatoxins using type II photocyclization reactions was reported by Kraus, in which dihydrobenzofuranols were obtained from aryl alkyl ketones via 1,5-hydrogen abstraction [124], An interesting reaction reported by Nicolaou involves preparation of the fused poly(oxacycle) systems employing electron transfer reaction of macrodithionolides as shown by the eventual synthesis of 188 from 186 [125] (Scheme 64). 

Nevertheless, it must be pointed out that the formation of such transient species has never been spectroscopically observed. Native CDs are effective inverse phase-transfer catalysts for the deoxygenation of allylic alcohols, epoxydation,or oxidation " of olefins, reduction of a,/ -unsaturated acids,a-keto ester,conjugated dienes,or aryl alkyl ketones.Interestingly, chemically modified CDs like the partially 0-methylated CDs show a better catalytic activity than native CDs in numerous reactions such as the Wacker oxidation,hydrogenation of aldehydes,Suzuki cross-coupling reaction, hydroformylation, " or hydrocarboxylation of olefins. Methylated /3-CDs were also used successfully to perform substrate-selective reactions in a two-phase system. 

Aryl alkyl ketones are reduced in up to 97% ee by transfer hydrogenation in ethanol (which is also the hydrogen donor), using an amino acid hydroxy amide ligand com-plexed to ruthenium(II)." ... 

Chiral ferrocenyl-NHC Ir and Rh complexes 50a-e were prepared by Chung and coworkers from optically pure ferrocenyl alcohols or acetates and applied in the transfer hydrogenation of aryl alkyl ketones (Scheme 3.27) [48]. The Ir complexes gave the corresponding products in higher enantioselectivities (up to 53% ee) than those obtained from the Rh complexes (only up to 10% ee). 

Recently Xiao and coworkers also reported a Rh(III) catalyst prepared by a combination of [Cp RhCl]2 and (lR,2R)-N-(p-toluenesulfonyl)l,2-cyclohexanediamine for the transfer hydrogenation of aryl alkyl ketones in air and water. 

A set of neutral mononuclear rhodium(i) complexes of the P-NH ligands were also prepared by the reaction of [Rh(cod)Cl]2 with an allqrl-substituted phenylaminophosphine (Scheme 9). The structures of the new complexes were elucidated by spectroscopic analysis. The complexes were applied to the transfer hydrogenation of acetophenone derivatives and aryl alkyl ketones in the presence of 2-propanol. Particularly, complex 35b behaved as an excellent catalyst, giving the corresponding alcohols with conversions of up to 99%. 

The quantum yields for oxetane formation have not been determined in every case, and only a few relative rate constants are known. The reactivities of singlet and triplet states of alkyl ketones are very nearly equal in attack on electron rich olefins. 72> However, acetone singlets are about an order of magnitude more reactive in nucleophilic attack on electron-deficient olefins. 61 > Oxetane formation is competitive with a-cleavage, hydrogen abstraction and energy-transfer reactions 60 64> so the absolute rates must be reasonably high. Aryl aldehydes and ketones add to olefins with lower quantum yields, 66> and 3n-n states are particularly unreactive. 76>... 

For alkyl aryl ketones, the use of the novel PennPhos rhodium catalyst afforded enantioselectivities of over 90 %, such as are routinely obtained by transfer hydrogenation [13], but, only for alkyl groups up to C2. This is in contrast... 

Some progress has been made, particularly with the ruthenium complex-catalyzed transfer hydrogenation [56] For tert-butyl methyl ketone as the first purely aliphatic ketone the bench mark of 90 % ee has been crossed by application of the oxazolinylferrocenylphosphine 28 the transfer hydrogenation by isopropanol under reflux in the presence of sodium hydroxide resulted in 93 % ee (S)-3,3-dimethyl-butan-2-ol [57]. For alkyl aryl ketones 92-95 % ee is obtained with... 

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