Chiral pyridines

Fig. 8-1. Schematic representations of the interaction of the (R)NapEtNH enantiomer guest with a chiral pyridine-18-crown-6 host (S,S)-1 and possible conformations of the (R)NapEt com-...

High enantiomeric excesses for the addition of chloride to meso-epoxides were also obtained with use of a planar-chiral pyridine N-oxide 17 developed by Fu... 

Chiral pyridine-based ligands were, among various Ar,AT-coordinating ligands, more efficient associated to palladium for asymmetric nucleophilic allylic substitution. Asymmetric molybdenum-catalyzed alkylations, especially of non-symmetric allylic derivatives as substrates, have been very efficiently performed with bis(pyridylamide) ligands. 

Pyridine-based N-containing ligands have been tested in order to extend the scope of the copper-catalyzed cyclopropanation reaction of olefins. Chelucci et al. [33] have carefully examined and reviewed [34] the efficiency of a number of chiral pyridine derivatives as bidentate Hgands (mainly 2,2 -bipyridines, 2,2 6, 2 -terpyridines, phenanthrolines and aminopyridine) in the copper-catalyzed cyclopropanation of styrene by ethyl diazoacetate. The corresponding copper complexes proved to be only moderately active and enantios-elective (ee up to 32% for a C2-symmetric bipyridine). The same authors prepared other chiral ligands with nitrogen donors such as 2,2 -bipyridines 21, 5,6-dihydro-1,10-phenanthrolines 22, and 1,10-phenanthrolines 23 (see Scheme 14) [35]. 

In conclusion, many chiral pyridine-based ligands have been prepared from the chiral pool and have been successfully tested as ligands for the copper- or rhodium-catalyzed cyclopropanation of olefins. Alfhough efficient systems have been described, sometimes leading interestingly to the major cis isomer, the enantioselectivities usually remained lower than those obtained with the copper-bis(oxazoline) system. 

Tao B, Lo MMC, Fu GC (2001) Planar-chiral pyridine N-oxides, a new family of asymmetric catalysts exploiting an rj -CsArs ligand to achieve high enantioselectivity. J Am Chem Soc 123 353-354... 

Hydrosilylation of dienes accompanied by cyclization is emerging as a potential route to the synthesis of functionalized carbocycles. However, the utility of cycliza-tion/hydrosilylation has been Umited because of the absence of an asymmetric protocol. One example of asymmetric cycUzation/hydrosilylation has been reported very recently using a chiral pyridine-oxazoUne ligand instead of 1,10-phenanthroline of the cationic palladium complex (53) [60]. As shown in Scheme 3-21, the pyridine-oxazoUne Ugand is more effective than the bisoxazoUne ligand in this asymmetric cyclization/hydrosilylation of a 1,6-diene. 

In contrast to the large number of chiral pyridine derivatives used as ligands of metal complexes in asymmetric catalysis, only a few examples of chiral sulfur-containing pyridine ligands have so far been reported, such as pyridine thioethers derived from ( + )-camphor depicted in Scheme 1.33, which were assessed in the test reaction providing enantioselectivities of up to 76% ee. The related 2,2 -bipyridine thioethers were also prepared but showed a lower stereodilferentiating capability in the test reaction. 

Pro-chiral pyridine A-oxides have also been used as substrates in asymmetric processes. Jprgensen and co-workers explored the catalytic asymmetric Mukaiyama aldol reaction between ketene silyl acetals 61 and pyridine A-oxide carboxaldehydes 62 <06CEJ3472>. The process is catalyzed by a copper(II)-bis(oxazoline) complex 63 which gave good yields and diastereoselectivities with up to 99% enantiomeric excess. 

Hydrosilylation of 1,6-dienes accompanied by cyclization giving a five-membered ring system is emerging as a potential route to the synthesis of functionalized carbocycles.81,81a,81b 82 As its asymmetric version, diallylmalonates 86 were treated with trialkylsilane in the presence of a cationic palladium catalyst 88, which is coordinated with a chiral pyridine-oxazoline ligand. As the cyclization-hydrosilylation products, //ww-disubstituted cyclopentanes 87 were obtained with high diastereoselectivity (>95%), whose enantioselectivity ranged between 87% and 90% (Scheme 25).83 83a... 

The first attempt to effect the asymmetric cw-dihydroxylation of olefins with osmium tetroxide was reported in 1980 by Hentges and Sharpless.54 Taking into consideration that the rate of osmium(VI) ester formation can be accelerated by nucleophilic ligands such as pyridine, Hentges and Sharpless used 1-2-(2-menthyl)-pyridine as a chiral ligand. However, the diols obtained in this way were of low enantiomeric excess (3-18% ee only). The low ee was attributed to the instability of the osmium tetroxide chiral pyridine complexes. As a result, the naturally occurring cinchona alkaloids quinine and quinidine were derived to dihydroquinine and dihydroquinidine acetate and were selected as chiral... 

Sharpless and Hentges proposed that the cyclic ester (112) is formed via an oxametallacy-clobutane (111) resulting from the [2 + 2] intramolecular addition of an oxo bond to the coordinated alkene in (110).345 They utilized the high stereoselectivity of this reaction to induce chirality with good optical yields (up to 83%) during the hydroxylation of various alkenes by 0s04 in the presence of chiral pyridine ligands.345... 

The application of the desymmetrization method can be extended to a bicyclic system containing two primary acetate leaving groups (Scheme 8E.16). By using the chiral pyridine-phosphine ligand 49, the diacetate could be converted into the allylic amine in 93% yield and 89% ee [70],... 

The reaction became enantioselective in the presence of a chiral pyridine-bis-(oxazoline) ligand yielding trans-(3-lactam with ee of 50%. 

Fig. 10 (a, b) Schematic mechanism demonstrated for a reflective color M-paper with magnetically controllable characteristics, (c, d) The intensity of magnetic field dependence on the reflection spectra of chiral nematic mixtures doped with magnetite nanoparticles that are surface modified with oleic acid and a chiral pyridine-based dopant, as well as photographs of both formulations before and after a magnetic field of 1,000 GS was applied (see photograph insets above) [364], (Copyright 2010, Taylor Francis)... 

On the basis of their observation that achiral 2,2 -bipyridyl promotes the reaction between crotyltrichlorosilane and benzaldehyde, the Barrett group screened chiral pyridine molecules as Lewis-base catalysts for this reaction [175]. The pyridinylox-azoline 164a was identified as the most efficient organocatalyst. In the presence of this catalyst, which was, however, used in stoichiometric amounts, asymmetric addition of (E)-crotyltrichlorosilane 158b to aldehydes gave the anti products (S,S)-159 in yields of 61-91% and with enantioselectivity from 36 to 74% ee (Scheme 6.76) [175], Diastereoselectivity is high, because only the anti diastereomers were obtained. Aromatic aldehydes and cinnamylaldehyde were used as substrates. 

In metal-free catalysis enantioselective ring-opening of epoxides according to Scheme 13.27 path B has been achieved both with chiral pyridine N-oxides and with chiral phosphoric amides. These compounds act as nucleophilic activators for tetrachlorosilane. In the work by Fu et al. the meso epoxides 71 were converted into the silylated chlorohydrins 72 in the presence of 5 mol% of the planar chiral pyridine N-oxides 73 (Scheme 13.36) [74]. As shown in Scheme 13.36, good yields... 

Methyl trichlorosilyl ketene acetal reacts with aromatic and aliphatic ketones (the former enantioselectively), using chiral pyridine bis-N-oxide catalysts.134 Computations and an X-ray crystal structure of a catalyst-SiCU complex have helped to elucidate the mechanism. 

A chiral pyridine-bisoxazoline ( PYBOX ) ligand has been combined with indium (III) triflate to produce an enantioselective catalyst for allylation of a wide variety of aldehydes in ionic liquids 183 ees of >90% were obtained, and extraction and reuse of the catalyst-ionic liquid combination saw this figure hold up to >80% on the fourth recycle. 

A series of planar chiral pyridine-fused ferrocene analogs (366) have been prepared and the enantiomers are resolved by chiral High performance (pressure) liquid chromatography (HPLC) see High Performance Liquid... 

Supramolecular coordination compounds with chiral pyridine and polypyridine ligands derived from terpenes 03CCR(242)87. 

The reactions proceed with retention of configuration at phosphorus. Various classical routes to alkylphosphine oxides have been applied in the synthesis of a range of potentially chelating and pincer-like ligands, e.g., (233), the binaphthyl system (234), the hybrid phosphine oxide-N-oxide (235), and the chiral pyridine bis(phosphine oxide) (236). A route to diarylmethylphosphine oxides is afforded by the palladium-catalysed reaction of aryl bromides with tet-rakis(hydroxymethyl)phosphonium chloride in the presence of a base. The diastereoisomeric system (237) has been isolated from the reaction of a cyclic... 

The first solid-phase synthesis of chiral pyridine-2,6-bis(oxazoline) (Pybox) ligands has been cleanly and efficiently performed in quite satisfactory overall yields and purity on polystyrene support, via a five-step synthetic sequence <05JOC4556>. 

Chiral pyridine addition to cobalt catalysts derived from dicobalt octacarbonyl has a positive influence on cherno- and regioselectivity, but not on stereoselectivity. Thus, no asymmetric induction is observed with Co ( + )-(.S )-3-.vtx-butylpyridine in the hydroformylation of styrene23. Again no induction is observed with chiral cobalt clustersl08. Cobalt is also used in catalytic systems of the type Co(An)n(alkene)m(CO)pLq [An = coordinating or noncoordinat-ing anions, e.g., BPhJ with various chiral ligands [L = ZR4R5R6 (Z = As, N, P, Sb)]166. Low catalytic activities and inductions are observed with supported catalysts of cobalt on silica gel or alumina [in situ preparation from salt, modified with phosphanes, e.g., (+)- or (—)-Diop]89. 

Polynuclear Complexes with Chiralized Pyridine and Polypyridine Ligands... 

Denmark and Fan (06TA687) reported that the oxidative dimerization of chiral pyridine N-oxides was highly diastereoselective for the formation of the P-configuration, (P)-(R,R)-260, of the chiral axis. 

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