2-methoxy-6-vinylnaphthalene

Variation in catalyst and ligand can lead to changes in both regio- and enantio-selectivity. For example, the hydroboration of vinyl arenes such as styrene and 6-methoxy-2-vinylnaphthalene can be directed to the internal secondary borane by use of Rh(COD)2BF4 as a catalyst.166 These reactions are enantioselective in the presence of a chiral phosphorus ligand. 

This same trend is produced upon addition of HCN to 4-isobutylstyrene, but in the case of 6-methoxy-2-vinylnaphthalene, all three ligands afford ca. 30% enantiomeric excess. 

The enantioselectivity increases dramatically when the ligands contain electron-withdrawing P-aryl substituents. Electron-donating substituents on the substrate give the highest ee (91% for 6-methoxy-2-vinylnaphthalene in apolar solvents). Mechanistic studies at room temperature have shown that at low concentration of HCN nickel zero species are the resting states, but at higher concentrations of HCN q3-benzyl nickel cyanide species were also observed. 

Although these reactions are highly versatile, so far they have not found significant industrial applications. The main reasons for this are relatively low thermal stabilities and turnover numbers of the catalytic systems, and the salt waste problem. However, Hoechst is trying to develop an industrial process for the manufacture of 6-methoxy 2-vinylnaphthalene by reaction 7.31. The precatalyst used is the dimeric phosphapallada cycle 7.63, which operates below a pressure of 20 atm and temperature of 130°C. 

There are several ways by which a palladium(II) species can be reduced to palladium(O). In the reaction to form 6 methoxy-2-vinylnaphthalene (Equation 11) reduction of the palladium(II) species to palladium(0) occurs with concomitant oxidation of the tertiary phosphine (Equation 15). 

HCN addition to 6-methoxy-2-vinylnaphthalene occurs readily at 25 °C in the presence of these optically active Ni complexes to give the branched nitrile exclusively and in high yield. The enantioselectivity (R versus S) of the... 

Methoxy-2-vinylnaphthalene (MVN) 30 is hydrocyanated under the catalytic influence of Ni° complexes 31a-e of 1,2-diol phosphinites that are derived from readily available mono- and di-saccharides. The sugar backbone and substitution of the phosphorus-attached aryl groups have a pronounced effect on the reaction pathway. It is shown that electron-withdrawing groups on the aryl ligands dramatically increase the stereoselectivity. As much as 85% ee was obtained when... 

The coupling of ethylene with 6-methoxy-2-bromonaphthalene (eq. (16)) is efficiently catalyzed by palladacycles 4. The ethylene reacts only once, thus yielding 6-methoxy-2-vinylnaphthalene in excellent selectivity and yield [57]. This elegant reaction is being developed as an industrial process by the former Hoechst AG, possibly the first industrial Heck coupling after the 30 years during which this type of reaction has been in existence. 

Another impressive exanqtle for the importance of electronic asymmetry in the design of chelating chiral ligands was reported by RajanBabu and Casalnuovo for the asymmetric hydrocyanation reaction . As chiral ligands 3,4-phosphinites from D-fructofiiranoside derivatives were synthesized. The unsymmetrical phosphinite with the more electron-deficient phosphorous at the C4-position of fiuctose gave superior enantioselectivities for the hydrocyanation of 6-methoxy-2-vinylnaphthalene. 

Similarly hydrovinylation of 4-isobutylstyrene or 6-methoxy-2-vinylnaphthalene, ozonolysis and oxidation gives ibuprofen (11) and naproxen (12) with high ee values5. 

Asymmetric hydroesterification of styrenes is suggested as an alternative route to optically active 3-arylbutanoic acids, a series of nonsteroidal anti-inflammatory drugs18. Thus, with palladium(0)bis(dibenzylideneacetone) in the presence of NMDPP and trifluoroacetic acid 6-methoxy-2-vinylnaphthalene gives the pharmaceutically interesting methyl (— )-2-(6-methoxy-2-naphthvl)propanoate (naproxen) with 42% ee20. 

Recently, ee s of 85-90% have been obtained for the asymmetric hydrocyanation of 6-methoxy-2-vinylnaphthalene using nickel complexes of chiral bidentate phosphinites derived from glucose (abbreviated PP, equation 12). This reaction is of great interest to the pharmaceutical industry because the S) enantiomer of the product nitrile is a useful precursor for the widely marketed antiinflammatory drug naproxen (equation 13). The same reaction can be applied to a number of other vinyl aromatic compounds, including the precursor for the antiinflammatory drug ibuprofen (6) however, the ee is not as high. 

The hydrocyanation of vinylarenes ° has been studied by a DuPont team using nickel catalysis. The hydrocyanation of 6-methoxy-2-vinylnaphthalene (2.219) affords the product (2.220), where the enantiomeric excess is strongly dependent upon the electronic nature of the bisphosphinite ligand (2.12). Hydrolysis of the nitrile (2.220) affords the nonsteroidal anti-inflammatory drug Naproxen. This nickel-catalysed procedure has also been applied with some success to the regiose-lective, asymmetric hydrocyanation of 1,3-dienes such as 1-phenyl-1,3-butadiene (2.221) to give the 1,2-adduct (2.222) with ees between 50 and 83%. ... 

---