Asymmetric norbomene

Ruthenium complexes mediate the hydroamination of ethylene with pyridine.589 The reaction, however, is not catalytic, because of strong complexation of the amine to metal sites. Iridium complexes with chiral diphosphine ligands and a small amount of fluoride cocatalyst are effective in inducing asymmetric alkene hydroamination reaction of norbomene with aniline [the best enantiomeric excess (ee) values exceed 90%].590 Strained methylenecyclopropanes react with ring opening to yield isomeric allylic enamines 591... 

With DIOP-Pd(0) or -Ni(0) complexes as catalysts, moderate optical yields of up to 35% have been observed (126). Norbomene is convertible to the exo nitrile with up to 40% ee when a BINAP-Pd(0) complex is used (Scheme 57) (127). Ni(0) complexes of sugar-derived 1,2-diol phosphinites catalyze highly selective asymmetric addition of hydrogen cyanide to vinylarenes (128). This method gives the 2-naphthalene-2-propionitrile precursors of nonsteroid anti-inflammatory agents in up to 85% ee and in high yield. 

One of the early examples of successful asymmetric catalyses is the codimerization of norbomene and ethylene catalyzed by a ir-allylnickel(II) hydride-organoaluminum chloride-chiral phosphine... 

Norbomanol with 96% ee was obtained by the asymmetric hydrosilylation of norbomene. Monofunctionalization of norbomadiene (565) was achieved with high chemo- and enantioselectivities to give uro-2-trich 1 orosilyl-5-norbornene (566) with one equivalent of trichlorosilane and converted to the alcohol 567 with 95% ee. With 2.5 equivalents, the chiral disilylnorbomane 568 was obtained rather than the me so isomer 569 (18 1). The disilylated product 568 was converted to the diol 570 with 99% ee [218],... 

In asymmetric hydrocyanation reactions the desired isomers are the chiral branched products only. Good regioselectivity toward the branched product (>98%) is limited to vinylarenes. Hydrocyanation of 1,3-dienes gives a variety of mixtures depending on the catalyst and conditions 1-alkenes give the linear nitrile as major product [34]. Both are seen in the adiponitrile process in which the unwanted branched 2M3BN (hydrocyanation product from 1,3-butadiene) is isomerized to the linear product 3-pentenenitrile, which is then hydrocyanated by in-situ isomerization to 4-pentenenitrile, resulting in the linear adiponitrile. Thus vinylarenes and cyclic alkenes (mainly norbomene) are usually the substrates of choice for the asymmetric hydrocyanation. Hopefully 1,3-dienes will become feasible substrates in the near future. 

Although a large number of chiral dienophiles have been developed (Table 26.2), their ability to provide high asymmetric induction appears to be limited to specific dienes. However, there are some dienophiles that tolerate a wider variety of dienes including menthol derivatives,117 118 camphor derivatives,6 39 40 105 107-113 181 182 and oxazolidinones.120 165 183 184 It should be noted that even these auxiliaries would require an efficient recycle protocol for economic scale up. One exception is the use of sacrificial chiral oxazolidinones, which are relatively inexpensive. This approach has been used in the large-scale preparation of the base cyclohexane unit of Ceralure Bj.168 A procedure has been developed for the preparation of (75,25)-5-norbomene-2-carboxylic acid where the D-panta-lactone auxiliary can be recycled efficiently.185186... 

The reaction can be carried out asymmetrically, using nickel complexes of chiral phosphite ligands. Examples are the enantioselective hydrocyanation of norbomene using ligand (22-XVIII),48 and of vinylnaphthalene derivatives with (22-XIX).49 The latter is a precursor for the anti-inflammatory drug naproxen. 

Also norbomene and related systems, as well as dihydrofuranes, have been hydrosilated with good enantioselectivities with similar MOP ligands. Intramolecular rhodium catalyzed asymmetric hydrosUations have been achieved with good enantioselectivities, for example with meso- or other allylsilylethers. ... 

Other Pd Derivatives and Related Reactions. Other chiral palladium complexes, such as (DIOP)2Pd° or (DIOP)(alkene)Pd°, can be prepared from (DIOP)PdCl2. These catalysts have afforded low levels of asymmetric induction (10% ee) in the hydro-cyanation of norbomene derivatives. ... 

Asymmetric Hydroboration. Hydroborations of alkenes by catecholborane have been catalyzed by [Rh(Cl)(cod)-(diphosphine)]. For example, norbomene gives, after oxidation, exo-norbomeol (82% ee) when a DIOP derivative (2-MeO-DIOP) was used (eq 5). Lower ee s were observed with DIOP, DIPAMP, and BINAP. The effectiveness of DIOP was also noticed in another report. ... 

Reaction of ethylene diacrylate, which is commercially available, and subsequent reduction with lithium aluminum hydride gives endo-5-norbomene-2-methanol with 78 % ee. Although it is not clear why selectivity is increased by the link between di-enophiles, similar effects are expected for other asymmetric reactions (Eq. 38). 

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

Even in the early days of homogeneous hydrocyanation the reaction of norbor-nene with hydrogen cyanide in the presence of tetrakisftriphenyl phosphite)palla-dium(O) 12 indicated the influence of steric factors, since exo-5-cyanobicy-clo[2.2.1]heptane (Structure 10) is obtained stereospecifically. This result was confirmed in similar reactions showing that the entering cyano group is directed into the exo-position of the norbomene system [28]. This is due to the complexa-tion of the palladium(O) center to the exo-face of norbomene. Recent experiments have also utilized the bicyclic system to demonstrate asymmetric hydrocyanation induced by chiral palladium diphosphine complexes. Depending on the applied ligand system 11-17, an enantiomeric excess (ee) up to 40% is obtained [25]. 

Pd-phosphine complexes with chiral phosphines (MDPP, e. g., menthyldiphe-nylphosphine) may also be used as catalysts for the asymmetric hydrosilylation of C=C bonds (alkenes, arylalkenes, norbomene, cycloalkadienes, and dienes) (e. g., [75, 76]), affording a relatively high yield and optical purity. 

Asymmetric Codimerizations. The use of Ni catalysts modified by an optically active phosphine in catalytic asymmetric syntheses, e.g., of the type [ NiX(rj -C3Hs) ij]/ Al2Cl3Et3/PR3, is important . Phosphines bearing the optical activity in the substituents such as 7 are most effective. Particularly high optical yields occur in the codimerization of C2H4 with a strained cyclic olefin such as norbomene [equation (a)] ... 

Substituted pyridylmethanols 3.72 have been recommended as ligands in nickel-catalyzed 1,4-additions of Et2Zn to a,P-unsaturated carbonyl compounds [112, 972], Asymmetric [2+2+2] cycloadditions of norbomene and acetylenes are catalyzed by a CotyZn/phosphine system and the most efficient ligands are amido-phosphinephosphinites prepared from (S)-valinol 1.60 (R = i-Pr, R = H) [973]. 

Asymmetric hydrosilylations of terminal alkenes, 1-arylalkenes, norbomenes and dihydrofurans with HSiCIj have been successfully performed by Hayashi and coworkers [914, 915, 916, 1340, 1341]. These reactions take place at 40°C when catalyzed by chiral palladium complexes, and the most efficient ligand is monophosphine 3.51 (R = Me) (Figure 7.19). The regioselectivity of the hydrosilylation of terminal olefins is opposite to that usually observed after treatment with H2O2/KF, secondary alcohols are obtained as major products [752, 855, 1340], The regioisomeric primary alcohols are typically formed in only about 10% yield in these reactions. 

Several other examples of palladium catalyzed asymmetric hydroarylations and hydroalkeny-lations of norbomene have been reported with up to 93% ee71,12. The same reaction type was used in stereoselective synthesis of epibatidine 1, a non-opiate analgesic alkaloid73. 

Acrylates. Cyclopentadiene is often used to evaluate selectivity in asymmetric Diels-Alder reactions. Table 6.4 lists the selectivities found for acrylate cycloadditions using the auxilieuies shown in Figure 6.13 under conditions that are optimized for each auxiliary. Note that there are four possible norbomene stereoisomers, two endo and two exo. In accord with Alder s endo rule, the endo is heavily favored in all these examples. Although several authors report selectivities in these reactions in terms of selectivity for one endo adduct over the other, the selectivities indicated in the table reflect the total diastereoselectivity of the major adduct over the other three, if this information could be deduced from the information provided in the paper. 

Asymmetric hydrosilylation of norbomene (2). This reaction can be effected in high regio- and enantioselectivity by reaction of 2 with CliSiH catalyzed by (allyl)chloropalladium dimer complexed with (R)-l. The product can be converted to (lS,2S,4R)-norbornanol (4) in 96% ee. 

Cyclopropanone acetals with a quaternary carbon atom in chiral form can be established by addition of bisoxazoline-ligated allylzinc reagents to the cyclopropenes.The t-BuLi/(-)-sparteine combination favors Br-Li exchange and also promotes enantioselection in the intramolecular addition of aryllithium to an o-alkenyl side chain (e.g., indoline synthe-j.ijj) I28.I29 Moderate asymmetric induction is shown in the hydroarylation of norbomene in the presence of 63. 

With the exception of norbomene, internal olefins do not undergo hydrosilylation. Hydrosilylation of 3-phenylpropene with PhSiDj forms a unique product and the process tolerates a variety of fianctional groups, halides, ethers and acetals, despite the well known strong Lewis acidity of the catalysts. Cyclisation/silylation of 1,5-dienes or 1,6-enynes has been reported to give a single product (Scheme 14) [26]. In the case of metallocene complexes bearing a menthyl substituent, ee values near 70% were obtained for the asymmetric hydrosilylation of 2-phenyl-but-l-ene [31]. 

Scheme 13 Pd(Josiphos)-catalyzed asymmetric hydrophosphinylation of norbomene...

Similar additions to alkenes have been reported with the same metals, Pd and Rh, including several Pd-catalyzed asymmetric syntheses. For example, Pd(Josi-phos) catalysts enabled enantioselective hydrophosphinylation of norbomenes (Scheme 13) [22]. 

The oligomerization of ethylene in the presence of nickel complexes with chelating P—P, P—0,0—0, and P—N ligands are the subject of a brief review. The asymmetric codimerization of ethylene and norbomene shown in equation... 

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