Aldehydes enantioselective halogenation

Alkylation with aldehyde 107 Alkylation, enantioselective 165 Alkylation, intramolecular 134,167 Enantioselective Mannich 151 From alcohol 26,41,86,176 From amide 11, 109,163 Halogenation, enantioselective 158... 

Burk et al. showed the enantioselective hydrogenation of a broad range of N-acylhydrazones 146 to occur readily with [Et-DuPhos Rh(COD)]OTf [14]. The reaction was found to be extremely chemoselective, with little or no reduction of alkenes, alkynes, ketones, aldehydes, esters, nitriles, imines, carbon-halogen, or nitro groups occurring. Excellent enantioselectivities were achieved (88-97% ee) at reasonable rates (TOF up to 500 h ) under very mild conditions (4 bar H2, 20°C). The products from these reactions could be easily converted into chiral amines or a-amino acids by cleavage of the N-N bond with samarium diiodide. 

Enantioselective -Functionalization of Aldehydes and Ketones The direct and enantiosective functionalization of enolates or enolate equivalents with carbon-, nitrogen-, oxygen-, sulfur- or halogen-centered electrophiles represents a powerful transformation of chemical synthesis and of fundamental importance to modem practitioners of asymmetric molecule constmction. Independent studies from List, J0rgensen, Cordova, Hayashi, and MacMiUan have demonstrated the power of enamine catalysis, developing catalytic enantioselective reactions such as... 

With benzaldehyde 144 or halogenated derivatives (Cl, F) as acceptors the yeast-PDC-catalyzed addition proceeds with almost complete stereoselectivity to furnish the corresponding (R)-configurated 1-hydroxy-1-phenylpropanones 145 [447]. For practical reasons, whole yeast cells are most often used as the catalyst, with only small loss of enantioselectivity [423,424]. The conversion of benzaldehyde in particular has gained industrial importance because the acyloin is an important precursor for the synthesis of L-(-)-ephedrine [448]. Otherwise, the substrate tolerance is remarkably broad for aromatic aldehydes on the laboratory scale, however, yields of acyloins are usually low because of the prior or consequent reductive metabolism of aldehyde substrate and product, giving rise to considerable quantities of alcohol 146 and vicinol diols 147, respectively [423,424,449], The range of structural variability covers both higher a-oxo-acids (e.g. -butyrate, -valerate) as the donor component, as well as a,/J-un-saturated aldehydes (e.g. cinnamaldehyde 148) as the acceptor [450]. 

Batch reactors based on peroxidases are mainly applied for degradation purposes (see Chap. 8). LiP, manganese peroxidase (MnP), HRP, SBP, and CPO were used for the oxidation of phenolic compounds [3, 6, 7, 9, 20, 38, 74, 75, 95], decoloriza-tion of dye-containing effluents [5, 22], and pulp biobleaching [59]. In the field of synthesis, CPO is the most versatile and promising of the peroxidases (see Chap. 6). It was applied in discontinuous operation for epoxidations [78,79], enantioselective oxidations of alcohols to aldehydes [14,48], halogenations [77,80], hydroxylations, and oxidation of indole to oxindole, which is an important drug precursor [96]. 

Asymmetric ene Reaction In 1988 Yamamoto and coworkers provided the first indication that asymmetry in ene-reactions could be induced by catalytic amounts of chiral Lewis acids in the presence of 4-A molecular sieves (Scheme 6.64) [88]. They described the first example of asymmetric ene-reaction between prochiral, halogenated aldehydes and alkenes catalyzed by chiral binaphthol-derived aluminum complexes. The hindered 3,3-silyl substituents in the chiral catalyst are essential to achieve good enantioselectivity and high yield. In fact, the use of a catalyst derived from MesAl and 3,3 -biphenylbinaphthol led to the racemic product in a low yield. 

The third subsection of this chapter discusses the a-funtionalisation of aldehydes and ketones. a-Oxidation, amination and halogenation have recently been achieved with high levels of enantioselectivity using enantiopure Lewis acids, or by generation of chiral nonracemic metal enolates, in the presence of a suitable electrophilic heteroatom source. Similar levels of selectivity in this transformation are obtained via the intermediacy of chiral enamines generated using organocatalysts. 

The organocatalyst-based a-functionalisation strategy has been applied with much success to the asymmetric halogenation of aldehydes. The imidazolidi-none salt (5.110) has been used by MacMillan and coworkers, in combination with NFSI, to effect enantioselective fluorination of a range of aldehydes, for example (5.111). ... 

Maruoka reported the organocatalytic enantioselective a-halogenation of aldehydes using NIS and the binaphthyl-based catalyst shown in Scheme 13.38 [77]. Additionally, the conditions for a-brominahon of aldehydes using the C2-syrmnetric chiral pyrrohdine catalyst depicted in Scheme 13.31 were adapted for the a-iodination of two aldehyde substrates [67]. 

P-Halogen Substituted Olefins Hydroformylation of 3,3,3-trifluoropropene with Rh(BINAPHOS) gives the corresponding branched aldehyde in excellent regio-and enantioselectivity (Scheme 4.86) [36]. The comparison of results obtained with the enantiomeric ligand gives an illustrative impression of the high reproducibility of the transformation. 

Aldehydes (Table 43.1) One of the most rapidly developing areas is the catalytic enantioselective a-halogenation... 

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