Regioselectivity asymmetric Heck reactions

Excellent enantioselectivity and double-bond regioselectivity can be achieved in an asymmetric Heck reaction between 2,3-dihydrofuran and aryl triflates by using a combination of chiral diphosphine-oxazoline ferrocenyl ligand and Pd catalyst <03CEJ3073>, as shown below. Chiral diphosphine-containing (arene)tricarbonylchromium(O) complexes were also used as ligands for this reaction to obtain the 2,3-isomer, however, both the yield and enantioselectivity were modest <03TA1455>. 

The first examples of asymmetric Heck reactions (AHRs) appeared around 20 years ago, reported almost simultaneously by Shibasaki and Overman. Equations 12.47105 and 12.48106 show these first efforts. Despite the modest enantioselectivi-ties observed, the transformations are notable because they show that tertiary and especially difficult to build quaternary centers can be constructed in a stereo- and regioselective manner. Equation 12.48 also shows an example of tandem Heck reactions in which two cyclizations occur in sequence. 

Another significant point of interest in the microwave enhanced Heck reaction is the asymmetric induction. A highly modular library of readily available phosphate oxazoline ligands was applied in the Pd-catalyzed asymmetric Heck reactions of several substrates and triflates under thermal and microwave conditions. Both enantiomers of the Heck coupling products showed excellent regioselective and enanti-oselective activities (Mazuela et al., 2010). 

Tu, T., Deng, W.-R, Hou, X.-L. et al. (2003) The regioselectivity of the asymmetric intermolecular Heck reaction with planar chiral diphosphine-oxazoline ferrocenyl ligands. Chem. Eur. J., 9, 3073 1. 

In an intermolecular Heck reaction, the nucleophilic component and the alkene are on different molecules. Until now, few applications of asymmetric intermolecular Heck reaction have been conducted, mainly because of problems related to the regioselectivity of this transformation. The first example reported by Hayashi and co-workers in 1991 involved the catalytic asymmetric arylation of 2,3-dihydrofuran 46. Aryl triflates afforded 2-aryl-2,3-dihydrofurans with enantioselectivities of up to 93% ee in the presence of the Pd(OAc)2/BINAP catalytic system. In a... 

The synthesis of lycorane (13) by Mori and Shiba-saki121 is breathtaking for its use of three consecutive Pd catalyzed C-C bond forming reactions. Thus, Pd-catalyzed asymmetric allylic substitution of a benzoate in meso 7 in the presence of the chiral bisphos-phine 8 leads to the regioselective formation of 10 in 40 % ee It is easy to overlook this low level of enantioselectivity when we are faced with the subsequent elegant Pd-catalyzed reactions Pd-catalyzed intramolecular animation is followed by a Pd-catalyzed Heck coupling to afford 12, which is then readily converted to the target molecule... 

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