Chiral tertiary amine ligands

The dihydroxylation of olefins with an osmium catalyst also utilizes chiral tertiary amine ligands to achieve high yields and enantioselectivity. Soon after Krief and coworkers reported on the coupled 02/PhSeCH2Ph oxidation [34], Bel-ler and coworkers discovered a direct 02-coupled catalytic aerobic oxidation of olefins was possible using a phosphate-buffered pH 10.4 solution (Scheme 5.21) [69]. Under increased pressure with air rather than O2, the catalyst remains active and a TOP of 40 h is possible. This system does not quite achieve as high an enantioselectivity as the AD-Mix methods [70]. 

The use of chiral tertiary phosphine ligands has been studied most widely, but other chiral ligands such as carboxylic acids (15), imines (8,16), amides (17), amines (18), alkoxides (19), and hydroxammates (13) have been investigated, and we reported recently on some sulfoxide systems (29, 21). 

Previous reviews have dealt with metal-catalyzed [93] and stoichiometric [94] oxidation of amines in a broad sense. This section will be limited to the selective oxidation of tertiary amines to N-oxides. Amine N-oxides are synthetically useful compounds [95, 96] and are frequently used as stoichiometric oxidants in osmium-[97-99] manganese- [100] and ruthenium-catalyzed [101,102] oxidations, as well as in other organic transformations [103-105]. Aliphatic tert-amine N-oxides are usefid surfactants [96] and are essential components in hair conditioners, shampoos, toothpaste, cosmetics, and so on [106]. Chiral N-oxides have been used in asymmetric catalysis involving metal-free catalytic transformations [107] as well as metal-catalyzed reactions where the N-oxide serves as a ligand [107, 108]. Chiral tertiary amine N-oxides were recently used as reagents in asymmetric epoxidation of a,(3-unsaturated ketones [109]. 

Suitable chiral tertiary amine catalysts for this rearrangement are cinchona-alkaloid derivatives, and Jorgensen et al. found that the best conditions involved the use of the well-known Sharpless [DHQDJ2PHAL ligand 18 and dioxane as solvent (Scheme 40.26). 

In summary, the reaction of osmium tetroxide with alkenes is a reliable and selective transformation. Chiral diamines and cinchona alkakoid are most frequently used as chiral auxiliaries. Complexes derived from osmium tetroxide with diamines do not undergo catalytic turnover, whereas dihydroquinidine and dihydroquinine derivatives have been found to be very effective catalysts for the oxidation of a variety of alkenes. OsC>4 can be used catalytically in the presence of a secondary oxygen donor (e.g., H202, TBHP, A -methylmorpholine-/V-oxide, sodium periodate, 02, sodium hypochlorite, potassium ferricyanide). Furthermore, a remarkable rate enhancement occurs with the addition of a nucleophilic ligand such as pyridine or a tertiary amine. Table 4-11 lists the preferred chiral ligands for the dihydroxylation of a variety of olefins.61 Table 4-12 lists the recommended ligands for each class of olefins. 

In the presence of a catalytic amount of chiral lanthanide triflate 63, the reaction of 3-acyl-l,3-oxazolidin-2-ones with cyclopentadiene produces Diels-Alder adducts in high yields and high ee. The chiral lanthanide triflate 63 can be prepared from ytterbium triflate, (R)-( I )-binaphthol, and a tertiary amine. Both enantiomers of the cycloaddition product can be prepared via this chiral lanthanide (III) complex-catalyzed reaction using the same chiral source [(R)-(+)-binaphthol] and an appropriately selected achiral ligand. This achiral ligand serves as an additive to stabilize the catalyst in the sense of preventing the catalyst from aging. Asymmetric catalytic aza Diels-Alder reactions can also be carried out successfully under these conditions (Scheme 5-21).19... 

Certain tertiary amines such as pyridine or a-quinuclidine accelerate the stoichiometric reaction between osmium tetroxide and olefins (86). An asymmetric olefin osmylation using stoichiometric amounts of cinchona alkaloids as the chiral ligands was described in 1980 (87a). Optical yields of up to 90% were attained with frans-stilbene as substrate. 

When chiral amines are used in the oxyamination reaction, stereogenicity is induced in the amination step and in this way optically active amino alcohols are obtained after oxidation69. An optically active secondary or tertiary amine can be used as a ligand for palladium in the intermediate 7t-complex, to which an excess of an achiral amine can be added (reagent-induced diastereoselectivity). Here, a pair of diastereomeric tt-complexes are formed which may be in equilibrium with each other, the degree of asymmetric induction is dependent on the ratio between the diastereomeric complexes and/or on their different reactivity. 

Arylamines. Primary," secondary, and tertiary arylamines have been prepared by Pd(0)-catalyzed IV-arylation methods. The most common and effective catalytic system contains (dbaljPd, r-BuONa, and a tertiary phosphine such as BINAP. The nucleophilic species for the synthesis of primary anilines is a Ti-N complex formed from (i-PrO) Ti, Li, and McjSiCl in THF under nitrogen at room temperature (8 h). N-Arylation of chiral secondary amines proceeds without affecting the stereocenters. Arylation with Arl is facile because it can be carried out at room temperature. More recent development indicates that employment of 2-dimethylamino-2 -dicyclohexylphosphinobiphenyl as ligand in the amination of unactivated chloroarenes under mild conditions is also possible. 

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