Asymmetric norbornadiene

Asymmetric hydrogenolysis of epoxides has received relatively little attention despite the utility such processes might hold for the preparation of chiral secondary alcohol products. Chan et al. showed that epoxysuccinate disodium salt was reduced by use of a rhodium norbornadiene catalyst in methanol/water at room temperature to give the corresponding secondary alcohol in 62% ee (Scheme 7.31) [58]. Reduction with D2 afforded a labeled product consistent with direct epoxide C-O bond cleavage and no isomerization to the ketone or enol before reduction. 

The virtue of performing the PKR in an enantioselective manner has been extensively elaborated during the last decade. As a result, different powerful procedures were developed, spanning both auxiliary-based approaches and catalytic asymmetric reactions. For instance, the use of chiral N-oxides was reported by Kerr et al., who examined the effect of the chiral brucine N-oxide in the intermolecular PKR of propargylic alcohols and norbornadiene [59]. Under optimized conditions, ee values up to 78% at - 60 °C have been obtained (Eq. 10). Chiral sparteine N-oxides are also able to induce chirality, but the observed enantioselectivity was comparatively lower [60]. 

Asymmetric hydrocyanation has now been achieved using norbornene and norbornadiene as substrates. The reduction of either [PdCl2(+)-DIOP] or PdCl2 in presence of (+)-DIOP led to a palladium(O) species formulated simply as [Pd(+)-DIOP]. This gave, in reaction (164), an optical yield of 30% for the 2-exo-cyanonorbornane formed. Norbornadiene with the same catalyst gave 2-exo-cyanonorborn-5-ene with an optical purity of 17%. When the ligand CHIRAPHOS (51) was used, the catalytic activity was greatly diminished.608,609 In addition to the review of the early work already mentioned, two more recent reviews of hydrocyanation have appeared.610,611... 

The asymmetric hydrosilylation of thiochroman-4-one catalyzed by a Rh norbornadiene (nbd) complex with a mixed P and S ligand occurs with both high enantioselectivity (92%) and yield (91%) (Equation 87) <2003JA3534>. Cr complexes with amino acids effect the reduction but with only low enantioselectivity <1999TL1373, 2004TA1735>. 

Chiral polymers have been applied in many areas of research, including chiral separation of organic molecules, asymmetric induction in organic synthesis, and wave guiding in non-linear optics [ 146,147]. Two distinct classes of polymers represent these optically active materials those with induced chirality based on the catalyst and polymerization mechanism and those produced from chiral monomers. Achiral monomers like propylene have been polymerized stereoselectively using chiral initiators or catalysts yielding isotactic, helical polymers [148-150]. On the other hand, polymerization of chiral monomers such as diepoxides, dimethacrylates, diisocyanides, and vinyl ethers yields chiral polymers by incorporation of chirality into the main chain of the polymer or as a pedant side group [151-155]. A number of chiral metathesis catalysts have been made, and they have proven useful in asymmetric ROM as well as in stereospecific polymerization of norbornene and norbornadiene [ 156-159]. This section of the review will focus on the ADMET polymerization of chiral monomers as a method of chiral polymer synthesis. 

Scheme 11.5 Stereoselective synthesis of cyclopentylamines via asymmetric hydroamination of norbornadiene [29].

Figure 2 Example of an asymmetric hydrogenation catalyst, [(S,S-CHIRA-PHOS)Rh(nobornadiene)]+. The norbornadiene ligand is used to represent the coordination of solvent molecules.

Asymmetric hydroarylation/hydrovinylation, although not strictly a Heck reaction as the P-hydride ehmination step is replaced by reductive ehmination, nevertheless shares a common mechanistic pathway with regard to the enantiose-lective step and so will be discussed briefly. In 1991 Brunner et al. first reported hydrophenylations of norbornene and norbornadiene using aryl iodides, al-... 

Asymmetric hydrovinylation of norbornene and norbornadiene leading exclusively to exo-vinyl products 4 and 5 has been reported with allylnickel systems using isopropylbis(men-thyljphosphane as chiral ligand4,5. Optical yields depend highly on temperature, highest enantiomeric excesses (up to 80.6%) are obtained at about — 70 =C. however with only low productivity. Furthermore, the products tend to isomerize to exo-methylene compounds under the reaction conditions. 

In a more detailed study, the structure of the catalyst precursor was determined and found to be Pd(Diop),32. Other L2Pd and L2Ni complexes [L = Diop, BPPM, BINAP, etc.] were prepared [e.g., by in situ reduction of Pd(Il)Cl,L with sodium borohydride or as isolated palladium(O) complexes] and used as catalysts for the asymmetric addition of hydrogen cyanide to norbornene. norbornadiene, benzonorbornadiene, and cyclopentadiene dimer. In the presence of excess ( + )-Diop and L,Pd, norbornene gives 91 -95% of exo-2-cyanonorbornane with 24% cc of the ( + )-(15.25,4/ )-isomer. Similarly, use of the ( —)-Diop complex leads to the (-)-(l/ ,2f ,4S)-isomer with 24% ee (95% yield). Lower reaction temperatures, instead of the 120 "C used above, give better ee values (80 =C 32% ee with 94% yield 35 °C 35 % ee with 6% yield)32. 

Several other examples of this reaction type have been reported96-98. The nortricyclene skeleton is also obtained in asymmetric rhodium(I)-catalyzed addition of phenylethvne to norbornadiene, if[Rh(nbd)(—)-Norphos]PF6 is used as catalyst51. This results in optically active 3-(phenylethynyl)tricyclo[2.2.1.02,6]heptane (21) in 45% yield and 60% optical purity. Replacement of (—)-Norphos by other diphosphanes leads to other products or product mixtures. 

It has been found that dichloro (R)-N,jV-dimethyl-l-([(S)-2-(diphenylphosphino) ferrocenyl]ethylamine palladium(II), 4PdCl2[(R)-(S)-PPFA] is an efficient catalyst for the asymmetric hydrosilylation of styrene and norbornadiene with trichlorosilane, which gives (S)-a-phenylethyltrichlorosilane and (lR,2S,4S)-norbornyltrichlorosilane, respectively, in good yields69. The hydrosilylation products thus obtained can be converted to the corresponding optically active alcohols through fluorosilicates without loss of optical activity (equations 24 and 25). 

Cobalt(II) iodide-triphenylphosphine-zinc systems catalyse the homo-Diels-Alder reaction of norbornadiene with alkynes R C=CR (R = Bu, Ph or SiMe3 R = H, Me or Et) to give the tetracyclic adducts 512. Asymmetric induction has been reported for the cobalt acetylacetonate-catalysed homo-Diels-Alder addition of 1 -hexyne to norbornadiene in the presence of the diphosphine (R)-(+)-Ph2PCH2CHMePPh2 to yield the dextrorotatory product 513 in 78% enantiomeric excess. Six new stereocentres are created in this... 

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