Substituted pyridines asymmetric hydrogenations

In recent years, a few stereoselective methods for the asymmetric hydrogenation of pyridines and related heterocycles have been developed <20050BC4171>. A chiral auxiliary method starts with an oxazolidinone-substituted pyridine which on reduction with H2/Pd(OH)2 in acetic acid affords the corresponding piperidine in good yield and high enantiopurity. The chiral auxiliary is cleaved during the reaction and can be recovered (Equation 100) <2004AGE2850>. 

The asymmetric hydrogenations of substituted pyridines would produce chiral... 

Scheme 10.38 Asymmetric hydrogenation of 2 oxazolidinone substituted pyridines.

Scheme 10.39 Asymmetric hydrogenation process of 3 substituted pyridine derivatives.

Synthesis of substituted piperidines Charette and co-workers recently reported a method for the preparation of substituted piperidines from activated pyridines. The method is based on an iridium-catalysed asymmetric hydrogenation of A-Iminopyr-idiniumylides 74 for the synthesis of enantiomerically enriched piperidines 75 [89] (Scheme 12.20). 

Asymmetric epoxidation of olefins with ruthenium catalysts based either on chiral porphyrins or on pyridine-2,6-bisoxazoline (pybox) ligands has been reported (Scheme 6.21). Berkessel et al. reported that catalysts 27 and 28 were efficient catalysts for the enantioselective epoxidation of aryl-substituted olefins (Table 6.10) [139]. Enantioselectivities of up to 83% were obtained in the epoxidation of 1,2-dihydronaphthalene with catalyst 28 and 2,6-DCPNO. Simple olefins such as oct-l-ene reacted poorly and gave epoxides with low enantioselectivity. The use of pybox ligands in ruthenium-catalyzed asymmetric epoxidations was first reported by Nishiyama et al., who used catalyst 30 in combination with iodosyl benzene, bisacetoxyiodo benzene [PhI(OAc)2], or TBHP for the oxidation of trons-stilbene [140], In their best result, with PhI(OAc)2 as oxidant, they obtained trons-stilbene oxide in 80% yield and with 63% ee. More recently, Beller and coworkers have reexamined this catalytic system, finding that asymmetric epoxidations could be perfonned with ruthenium catalysts 29 and 30 and 30% aqueous hydrogen peroxide (Table 6.11) [141]. Development of the pybox ligand provided ruthenium complex 31, which turned out to be the most efficient catalyst for asymmetric... 

The N,P phosphine-oxazoline chelate (59) is chiral, and complexes can act as homogeneous catalysts for asymmetric synthesis the Ir(l) and Pd(II) complexes promote enantioselective olefin hydrogenation and allylic substitution respectively. An N,P analog of the N,N didentate ligand 2,2 -bipyridine is (60), the soft P donor helping to stabilize low-valent metals. Further, 2,2-bipyridine derivatives such as (61) can bind metals such as Ir and Ru as N,C chelates with one pyridine nitrogen rotated to the opposite side, away from the metal ion. 

Chiral pyridylphosphines which incorporate a soft 71-acceptor and a relatively harder c-donor have been attracting interest in view of their applications in asymmetric catalytic scenarios such as allylic substitution, hydrogenation, hydrosilylation, hydroboration, etc., [61-68]. The hydrophosphination of (f)- -phenyl-3-(pyridin-2-yl)-2-propenone and methyl ( )-3-(pyridin-2-yl)-2-propenoate has been conducted as shown in Scheme 11 [69]. Interestingly, the fonner gave stereoisomeric five-membered P-N bidentate products in the ratio of 8 1 (major isomer shown in Scheme 11) while the latter gave exclusively one chiral six-membered P-N chelate product. 

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