Tethered chiral ligands

Half-sandwich Complexes with Tethered Chiral Ligands... 

The makeup of Mo-based complexes, represented by 1 [3], offers an attractive opportunity for the design, synthesis, and development of effective chiral metathesis catalysts. This claim is based on several factors 1) Mo-based catalysts such as 1 possess a modular structure [4] involving imido and alkoxide moieties that do not disassociate from the metal center in the course of the catalytic cycle. Any structural alteration of these ligands may thus lead to a notable effect on the reaction outcome and could be employed to control selectivity and reactivity. 2) Alkoxide moieties offer an excellent opportunity for incorporation of chirality within the catalyst structure through installment of non-racemic tethered chiral bis(hydroxy) ligands. 3) Mo-based complexes provide appreciable levels of activity and may be utilized to prepare highly substituted alkenes. 

The chelate effect of tethered Cp ligands may be used to modulate the coordination sphere in order to stabilize reactive metal centres and may also serve to introduce chirality at a metal centre. A number of reviews are available.4 11... 

Chiral moieties have been tethered onto MCM-41 surface in order to obtain optically active supported catalysts possessing the intrinsic texture brought by this particular support.2 >23 24 26 41-43 Thomas et al26,41 have developed a very interesting methodology to anchor a chiral ligand l,r-bis(diphenylphosphino)ferrocene to the inner walls of MCM-41 silica (Figure 1). 

The expected hexacarbonyl dicobalt complex was formed when the al-kyne and dicobalt octacarbonyl were stirred in CH2C12 (73 —> 74). If the same reaction was performed in the presence of ten equivalents of NMO, the novel pentacarbonyl complex could be isolated (73->75). On dissociation of the CO ligand, accelerated by the addition of NMO, the sulfur atom is able to coordinate to the vacant site creating a stable complex. Treatment of the complex with CO resulted in regeneration of the hexacarbonyl complex and, unlike the isolated alkene-pentacarbonyldicobalt-alkyne species 68, heating of the pentacarbonyl complex 75 led to the formation of the desired cyclopentenone. A similar sulfur stabilised intermediate was isolated by Pericas and co-workers while investigating tethered chiral auxiliaries in the PK reaction.87,88... 

A way to confer enantiofacial selectivity in cyclizations of achiral olefinic organolithi-ums is by the use of chiral ligands. The ability to discriminate between the enantiotopic faces of an inactivated carbon—carbon jr-bond tethered to a formally carbanionic center considerably extends the synthetic utility of anionic cyclizations119. 

The famous ligand BINAP controls an intramolecular Heck reaction to give decalin derivatives with good enantiomeric excess. BINAP is the optically pure phosphine built into the palladium catalyst. The presence of silver ions accelerates the reaction as well as preventing double bond isomerization in the original substrate. This time the chiral ligand selects which double bond is to take part in the reaction. The vinyl palladium species is tethered to the alkene and can reach only the same face. The faces of the alkenes are diastereotopic but the two alkenes are enantiotopic and you must know your right from your left to choose one rather than the other. 

Another more recent publication reported the grafting of chiral Rh complexes on silica gel via hydrogen bonding [50]. Different chiral ligands (Fig. 13) were converted to Rh trifluoromethanesulphonate complexes and immobilized applying the same immobilization technique mentioned above, the anionic part tethered non-covalently to the surface of the silica particles. Those complexes were applied in the hydrogenation of (E)-a-phenylcinnamicacid to... 

The enormous potential of the intramolecular Heck reactions has been demonstrated impressively in elegant syntheses of even the most complicated natural product skeletons. The intramolecular Heck reaction on the achiral iodoalkenes 354 and the corresponding alkenyl triflates 357 with their pairs of enantiotopic double bonds in the cyclohexa-1,4-diene moieties, applying catalysts with chiral ligands, gave tetrahydronaphthalenes 359 or hydrindanes from precursors such as 354, 357 or corresponding precursors with one less carbon in the tether [204f], with excellent enantioselectivities. Complementary to the asymmetrically induced inter-molecular arylation with triflates (Scheme 8.72), reasonable asymmetric inductions in intramolecular reactions were also achieved with iodides on the addition of silver salts to promote the formation of cationic intermediates such as 356 (Scheme 8.73)... 

Branched hydroformylation inttoduces a new stereogenic centre and, therefore, there is the opportunity to control the new centre by the use of chiral ligands. An early application of this concept is in an industrial synthesis of the anti-inflammatory drug, naproxen 4.193 from the corresponding styrene (Scheme 4.69). The ligand for the hydroformylation reaction, chiraphite 4.194, consisted of two bulky phosphates linked by a chiral tether. Many other chiral ligands have been developed. A problem with generating aldehydes with an a-chiral centre is their facile racemization via their enol or enolate form. One solution to this problem is to protect the product as its acetal 4.195 in situ (Scheme 4.70). ... 

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