Dimethylamino chiral derivatives

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... 

It is known that 5-acyloxyoxazoles 132 rearrange to 4-acyl-5(4/l/)-oxazolones 133 in the presence of 4-(dimethylamino)pyridme or 4-(pyrrohdino)pyridine. Recently, an asymmetric variant of this nucleophUe-catalyzed rearrangement that employs a chiral derivative of 4-(pyrrolidino)pyridine has been described. This procedure allows the construction of quaternary stereocenters with high levels of enantioselectivity (Scheme 7.38). Representative examples of saturated 5(4//)-oxazolones prepared via sigmatropic rearrangements are shown in Table 7.16 (Fig. 7.18). 

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

A variety of methods have been developed for the selective installation of chirality at oxindole C3 that involve transfer of functionality from indole C2. The Vedejs group has prepared a small collection of chiral DMAP (4-(lV,A-dimethylamino) pyridine) derivatives bearing conformationally restricted side chains that have been employed as nucleophilic catalysts to direct the transfer of indolyl C2 acetate or carboxylate groups to oxindole C3 with excellent enantiofacial selectivity [15]. As illustrated in Scheme 1, indolyl acetate 1 was converted to the chiral oxindole 3 (94%, 91% ee) using DMAP catalyst 2, while the opposite sense of enantioselec-tivity was observed when indolyl carboxylate 4 was treated with DMAP catalyst 5 to afford 6 as the major oxindole adduct (99%, 94% ee). In addition to probing modifications of the DMAP side chains, it was demonstrated that the overall rate of the reaction catalyzed by DMAP 2 was decreased when the indolyl acetate 1 contained a branched isopropyl substituent at C3 however, good enantioselectivity was observed with the branching substituent (82%, 94% ee). It was also... 

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

Another possibility for asymmetric reduction is the use of chiral complex hydrides derived from LiAlH. and chiral alcohols, e.g. N-methylephedrine (I. Jacquet, 1974), or 1,4-bis(dimethylamino)butanediol (D. Seebach, 1974). But stereoselectivities are mostly below 50%. At the present time attempts to form chiral alcohols from ketones are less successful than the asymmetric reduction of C = C double bonds via hydroboration or hydrogenation with Wilkinson type catalysts (G. Zweifel, 1963 H.B. Kagan, 1978 see p. 102f.). 

Addition reactions to aldehydes in the presence of the tartaric acid derived chiral auxiliaries (.S ..S )-l,2,3,4-tetramethoxybutane (5), (S,.S)-2,3-dimethoxy-A%V,/V, A,, -tctramethyl-l,4-bu-tanediamine (6) and (5,5)-2,3-bis[2-(dimethylamino)ethoxy]-Af,yV,A. iV -tetramethyl-l,4-bu-tanediamine (7) have been studied in detail9" u. Again there was low enantioselection (generally 10-55% ee). 

The combination of the enantiomerically pure 7V-methylephedrine derived silylketene acetal l-[(l/ ,2S)-2-dimethylamino-1-phenylpropoxy]-l-triniethylsilyloxy-l-propene with the chiral aldehyde (,R)-3-benzyloxy-2-methylpropanal leads, after reduction with lithium aluminum hydride, to the formation of a single 1,3-pentanediol 9 ( matched pair ). 

The reaction of racemic Sb-chiral l-phenyl-2-trimethylsilylstibindole with the optically active ortho-palladated benzylamine derivative, di-p-chlorobis (S)-2-[l-dimethylamino)ethyl]phenyl-C,N dipalladium, leads to diastereomeric complexes which were used for the separation of the enantiomers of the stibindoles.65 The molecular structures of the diastereomeric palladium complexes are depicted in Fig. 4. 

Kwakman et al. [65] described the synthesis of a new dansyl derivative for carboxylic acids. The label, N- (bromoacetyl)-A -[5-(dimethylamino)naphthalene-l-sulfonyl]-piperazine, reacted with both aliphatic and aromatic carboxylic acids in less than 30 min. Excess reagent was converted to a relatively polar compound and subsequently separated from the derivatives on a silica cartridge. A separation of carboxylic acid enantiomers was performed after labeling with either of three chiral labels and the applicability of the method was demonstrated by determinations of racemic ibuprofen in rat plasma and human urine [66], Other examples of labels used to derivatize carboxylic acids are 3-aminoperylene [67], various coumarin compounds [68], 9-anthracenemethanol [69], 6,7-dimethoxy-l-methyl-2(lH)-quinoxalinone-3-propionylcarboxylic acid hydrazide (quinoxalinone) [70], and a quinolizinocoumarin derivative termed Lumarin 4 [71],... 

If an achiral ferrocene derivative is converted to a chiral one by chiral reagents or catalysts, this may be called an asymmetric synthesis. All asymmetric syntheses of ferrocene derivatives known so far are reductions of ferrocenyl ketones or aldehydes to chiral secondary alcohols. Early attempts to reduce benzoylferrocene by the Clemmensen procedure in (5)-l-methoxy-2-methylbutane as chiral solvent led to complex mixtures of products with low enantiomeric excess [65]. With (25, 3R)-4-dimethylamino-l,2-diphenyl-3-methyl-2-butanol as chiral modifier for the LiAlH4 reducing agent, the desired alcohol was formed with 53% ee (Fig. 4-9 a) [66]. An even better chiral ligand for LiAlH4 is natural quinine, which allows enantioselective reduction of several ferrocenyl ketones with up to 80% ee [67]. Inclusion complexes of ferrocenyl ketones with cyclodextrins can be reduced by NaBH4 with up to 84% enantioselectivity (Fig. 4-9 b) [68 — 70]. 

---