Planar-chiral 4- pyridine

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... 

The [Fe-Cp]-fragment does not only play the role of an additional steric element introducing planar chirality into the otherwise flat pyridine system. Substitution at the pyridine 2-position usually cuts the nucleophilicity of the nitrogen atom thus limiting the possibilities to achieve efficient chirality transfer using nucleophilic pyridine catalysts [84]. Ferrocene, however, functions as a strong electron donor (see Sect. 1) and thus restores the nucleophilicity impaired by substitution. 

Wurz RP, Lee EC, Ruble JC, Fu GC (2007) Synthesis and resolution of planar-chiral derivatives of 4-(dimethylamino)pyridine. Adv Synth Catal 349 2345-2352... 

Ruble JC, Fu GC (1998) Enantioselective construction of quaternary stereocenters rearrangements of 0-acylated azlactones catalyzed by a planar-chiral derivative of 4-(pyrrolidino) pyridine. J Am Chem Soc 120 11532-11533... 

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... 

Hence, the group developed a series of planar chiral ferrocenyl 4-DMAP and 4-(pyrrolidino)pyridine (4-PPY) derivatives (15-18) that have proved to be highly versatile and efficient catalysts for many acyl transfer processes (Fig. 5) [25, 26, 66-82, 93, 99, 103, 105]. 

Planar-chiral derivatives of 4-(pyrrolidino)pyridine (PPY) have been reported as efficient catalysts for enantioselective Staudinger reactions [75]. These chiral derivatives catalyzed the reactions between a range of symmetrical and unsymmet-rical disubstituted ketenes and a wide imine array leading to (3-lactams with good stereoselections and yields. 

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... 

In 1998 Fu and Ruble reported that the planar chiral 4-(diakylamino)pyridine derivatives 79a and 79b (Scheme 13.42) induce high enantiomeric excesses in the catalytic O-acyl azlactone rearrangement [85, 86]. In particular with the PPY-derivative 79b, O-acyl azlactones 80 were smoothly rearranged to the products 81 in almost quantitative yields and enantiomeric excesses up to 92% (Scheme 13.42) [85]. 

It has also been demonstrated that a planar-chiral azaferrocene derivative of 4-(pyrrolidino)pyridine is an excellent catalyst for the enantioselective Staudinger reaction, providing P-lactams 24 with very good stereoselection and yield <02JACS1578>. 

Simple amines can rapidly add to ketenes in the absence of a catalyst, but less reactive nitrogen nucleophiles such as the pyrroles do not react at room temperature with ketenes such as phenyl ethyl ketene <2002JA10006>. In contrast, additions can proceed swiftly when planar chiral 4-(pyrrolidino)pyridine (PPY) derivative 235 is employed as a catalyst (Equation 58). In the presence of enantiopure PPY derivative 235 and an appropriate pyrrole, the A -acylpyrroles 236 and 237 can be generated in high enantiomeric excess (Equations 58 and 59) <2002JA10006>. With pyrrole itself as the nucleophile, the new stereocenter is produced in moderate ee (42%). It was discovered that l-acyl-l/7-pyrrole-2-carbonitriles 236 can be converted into a wide array of useful compounds with essentially no erosion in enantiomeric excess. 

Naturally, it is possible to synthesise a similar ligand system without central chirality and in fact without the unnecessary methylene linker unit. A suitable synthesis starts with planar chiral ferrocenyl aldehyde acetal (see Figure 5.30). Hydrolysis and oxidation of the acetal yields the corresponding carboxylic acid that is transformed into the azide and subsequently turned into the respective primary amine functionalised planar chiral ferrocene. A rather complex reaction sequence involving 5-triazine, bromoacetal-dehyde diethylacetal and boron trifluoride etherate eventually yields the desired doubly ferrocenyl substituted imidazolium salt that can be deprotonated with the usual potassium tert-butylate to the free carbene. The ligand was used to form a variety of palladium(II) carbene complexes with pyridine or a phosphane as coligand. 

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... 

Fu GC. Asymmetric catalysis with Planar-chiral derivatives of 4-(Dimethylamino)pyridine. Acc. Chem. Res. 2004 37 542-547. 

In 1993, Vedejs et al. [5,6] showed that tributylphosphine is a potent catalyst for the acylation of alcohols by acetic and benzoic anhydrides as efficient as 4-(di-methylamino)pyridine DMAP [7,8]. However, the DMAP catalyst is more versatile since it presents catalytic activity in the reaction of alcohols with a larger variety of electrophiles. Due to these properties, Fu [9] realized the design and synthesis of a new family of chiral nucleophilic catalysts illustrated by the planar-chiral DMAP derivative I which is a very efficient catalyst in different enantioselective reactions such as addition of alcohols to ketenes [10], rearrangement of O-acylated azalactones [11], and kinetic resolution of secondary alcohols [12-14]. 

In 2002, Hodous and Fu and co-workers reported the enantioselective addition of amines to ketenes catalyzed by the planar chiral 4-(pyrrolidino) pyridine derivative 12 (Figure 10.12) to furnish acylpyrroles with good to excellent enantioselectivities (Equation 10.26) [54],... 

Finally, a completely new use of planar-chiral ferrocenes has been recently disclosed by Fu and co-workers [24]. Compounds of type 25 and 26 were prepared as racemic mixtures and obtained as pure enantiomers via semipreparative HPLC. Derivatives 25, analogues of 4-(dimethylamino)pyridine, were used as nucleophilic catalysts in the kinetic resolution of chiral secondary alcohols [24a,b]. The ami-noalcohol system 26, on the other hand, is an effective chiral ligand for the asymmetric addition of dialkylzinc reagents to aldehydes (up to 90% ee) [24c]. 

On this topic, several outstanding contributions were reported by Fu and coworkers,in which new asymmetric nucleophilic catalysts based on chiral ferrocene-type heterocycles were designed. To this end the planar-chiral PPY ferrocene complex (PPY = 4-(pyrrolidino)-pyridine (3.61) was prepared and resolved. Complex 3.61 catalysed the enantioselective rearrangement of A-acylated Azlactones to give C-acylated isomers with high yields and ee of 82-90%. The powerful effect of the chiral ferrocene scaffold was clearly evident if compared to the same reaction with the organic catalyst DMAP reported in 1970 by Steglich and Hofle where only racemic compounds were formed (Scheme 3.26). 

Fu GC (2004) Asymmetric Catalysis with Planar-Chiral Derivatives of 4-(Dimethylamino) pyridine. Acc Chem Res 37 542... 

A mimetic reaction has been developed extensively and is known to proceed with the aid of a metal ion such as Zn(II). As has been achieved in the stereoselective reductions by NAD(P)H-models in which one of enantiofaces is frozen, freezing of a face of the pyridine ring in pyridoxal or its model compound will result in the stereoselective mimetic transamination. Kuzuhara and his co-workers have synthesized pyridoxamine analogues that have planar chirality and have succeeded in observing asymmetric transamination (Iwata et al. 1976, Kuzuhara et al. 1977, 1978, Sakurai et al. 1979, Ando et al. 1982, Tachibana et al. 1982a,b, Breslow et al. 1980). The reaction is shown in Scheme 31 and the results are summarized in Table 30. 

Catalytic enantioselective cycloaddition reactions of ketenes have been intensively explored over the past several decades. Various chiral catalysts have been developed for these cycloadditions, such as cinchona alkaloids, N-heterocyclic carbene (NHC) catalysis (2013SL1614), planar-chiral 4-(JV,JV-dimethylamino)pyridine (DMAP)-derived catalysts, and Lewis acid-based catalysts (2009T6771, 2004ACR542). 

Heteroleptic heterodinuclear m-Pd (C N)2 complexes such as 56 are obtained from the reaction of or/i o-mercurated 2-[(77 -phenyl)tricarbonylchromium]pyridine with /x-chloro cyclopalladated aromatic compounds in the presence of large amounts of [NMe4]Cl. The products are valuable precursors of planar chiral cyclopalladated Gr( 7 -arene)(GO)3 complexes, for example, 57. A series of or// o-palladated binuclear Gr(r7 -arene)(GO)3... 

A computational study of the addition of pyrrole to ketene Ph(Me)C=C=0, catalysed by the planar-chiral 4-(pyrrolidino)pyridine (468), suggests that the enantioselection (81% ee) is controlled by a combination of stereoelectronic effects and CH-O interactions. A chiral Brpnsted acid complex has been identified as the resting state of the catalyst. ... 

Teuben et al. reported a related reaction, in which the thermolysis of alkyl-bis(pentamethylcyclopentadienyl)titanium(III) caused a dissociation of alkane with formation of 64. further heating at 150°C resulted in hydrogen dissociation and formation of 70 as a diamagnetic material. Subsequent reaction with acetophenone gave chelate complex 71 in 60% yield, which was fully characterized spectroscopically as well as by an X-ray structure analysis (Scheme 10.24). Interestingly, the authors do not mention the presence of two diasteromers, although the alkyl chain bears an asymmetric carbon atom in addition to the planar chirality of the metallocene. Similar reactions were observed with pyridine derivatives [72]. 

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