Enantioselective Fluorous Catalysis

Besides the use of fluorous catalysts, the characteristics of which will be briefly outlined in the next section, two features of the original FBS concept are also worth mentioning  

Handbook of Asymmetric Heterogeneous Catalysis. Edited by K. Ding and Y. Uozumi Copyright 2008 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 978-3-527-31913-8 

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The possibility of asymmetric induction under the fluorous biphase conditions was first speculated upon by Horvath and Rabai [10], and this year has seen the first report of asymmetric catalysis in a fluorous biphase [69]. Two, C2 symmetric salen ligands (29a, b) with four C8Fi7 ponytails have been prepared (Scheme 5) and their Mn(II) complexes evaluated as chiral catalysts for the aerobic oxidation of alkenes under FBS-modified Mukaiyama conditions. Both complexes are active catalysts (isolated yields of epoxides up to 85%) under unusually low catalyst loadings (1.5% cf. the usual 12%). Although catalyst recovery and re-use was demonstrated, low enantioselectivities were observed in most cases. 

When the chemoselectivity hypothesis was tested with cyclohexane as the substrate and Rh2(OPiv)4 (25d) as the catalyst, it was shown to be true (Table 2) [80], Although the reaction with EDA produced predominantly carbene dimer 76 (entry 1), 94% of the C-H insertion product 75 was isolated with methyl phenyldia-zoacetate as the carbenoid precursor under identical reaction conditions (entry 3). This simple comparison indicated that the donor/acceptor carbenoids are indeed more stable and less prone towards undesired dimerization events. Another feature of the donor/acceptor carbenoids that is not shared by EDA is the fact that the carbenoid carbon possesses two substituents. This opens up the opportunity for asymmetric catalysis to occur. Indeed, when a number of aryldiazoacetates 74 were decomposed with Rh2(,S -D0SP)4 (26) in the presence of cyclohexane, up to 95% ee was achieved for 77 [79, 81]. A fluorous prolinate catalyst was also developed to facilitate purification, but the enantioselectivities were not as high [82],... 

Enantioselective organocatalytic a-chlorination of aldehydes, via enamine catalysis, was independently reported by the groups of MacMillan and Jprgensen in 2004 (Scheme 13.20) [46, 47]. MacMillan utilized his imidazolidinone catalyst and a perchlorinated quinone as the chlorine source, to obtain the S-enantiomer of the a-chloroaldehyde products. Jprgensen employed NCS as the chlorine source, and either a prolinamide catalyst to access the / -enantiomer of the a-chloroaldehyde products, or a Ci-symmetric amine catalyst to access the 5-enantiomer. A recyclable fluorous pyrrolidine-thiourea bifunctional organocatalyst was later employed as an enamine catalyst in this transformation [48]. 

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