Optical activity heterocyclic acids

The highly enantioselective hydrogenation of unsaturated N-heterocyclic acids and 0-heterocyclic acids under H2 with CS2CO3 as additive and chiraliridium/spirophosphine oxazoline complexes as catalyst provide an efficient method for the preparation of optically active heterocyclic acids with up to 99% ee. The concise syntheses of (7 )-nipecotic acid and (/ )-tiagabine demonstrate that this catalytic asymmetric reaction has the potential for wide application in organic synthesis." ... 

Pubhcations have described the use of HFPO to prepare acyl fluorides (53), fluoroketones (54), fluorinated heterocycles (55), as well as serving as a source of difluorocarbene for the synthesis of numerous cycHc and acycHc compounds (56). The isomerization of HFPO to hexafluoroacetone by hydrogen fluoride has been used as part of a one-pot synthesis of bisphenol AF (57). HFPO has been used as the starting material for the preparation of optically active perfluorinated acids (58). The nmr spectmm of HFPO is given in Reference 59. The molecular stmcture of HFPO has been deterrnined by gas-phase electron diffraction (13). 

Recently, an asymmetric version of this reaction has been reported by Gong and co-workers, allowing an efficient access to highly enantiomerically enriched 4-aryl-substituted 1,4-DHPs [152]. Thus, the use of chiral phosphoric acids as catalysts allowed the preparation of the desired products with enantiomeric excesses up to 97% (Scheme 53). To illustrate the importance of this asymmetric cyclization reaction, the authors developed the synthesis of some optically active heterocycles... 

Subsequently the heterocycle is cleaved by hydrolysis to liberate the chiral auxiliary and the new optically active amino acid. 

Transfer of a halonium ion to l,o)-alkenols or l,co-alkenoic acids which are capable of undergoing halocyclization is a key method to generate 4-, 5- and 6-membered heterocyclic rings via the so-called halocyclization processes 1,2,3,4,5,6,7). This synthetic method would be far more valuable if the halogen transfer to an achiral alkene could be conducted in a chiral fashion (exemplified in Figure 1) as it would produce optically active heterocycles that could be further functionalized through manipulation of the halomethyl group. 

Of particular importance to heterocyclic chemistry is the labeling of optically active amino acids. Preliminary results5 42 with methionine, proline, tryptophan, and glutamic acid show that significant racemization can occur even in the crystalline phase. In a systematic study of the... 

Turning to carbon-carbon bond formation, Schollkopf et al. ° have provided an asymmetric synthesis of a-amino-acids via alkylation of an optically active heterocyclic system (49) as indicated optical yields were high. The Diels-Alder... 

Racemic and optically active a-aminophosphonic acids, derivatives of various heterocycles 97ZOR1605. 

In Table IV some physical data and spectral characteristics of 6,7-secoberbines are listed. Only methyl corydalate (55) is optically active. Formula 55 presents the spatial structure of this compound, deduced by Nonaka et al. (65) and confirmed by Cushman et al. by both correlation with (+)-mesotetrahydrocorysamine (72) (<5S) and total synthesis (69). It is difficult to find common characteristic features in both the mass and H-NMR spectra of these alkaloids because they differ significantly from each other in their structures. On one hand, corydalic acid methyl ester (55) incorporates a saturated nitrogen heterocycle, while the three aromatic bases (56-58) differ in the character of the side chain nitrogen. For example, in mass fragmentation, ions of the following structures may be ascribed to the most intensive bands in the spectrum of 55 ... 

If the alkenes and acetylenes that are subjected to the reaction mediated by 1 have a leaving group at an appropriate position, as already described in Eq. 9.16, the resulting titanacycles undergo an elimination (path A) as shown in Eq. 9.58 [36], As the resulting vinyltitaniums can be trapped by electrophiles such as aldehydes, this reaction can be viewed as an alternative to stoichiometric metallo-ene reactions via allylic lithium, magnesium, or zinc complexes (path B). Preparations of optically active N-heterocycles [103], which enabled the synthesis of (—)-a-kainic acid (Eq. 9.59) [104,105], of cross-conjugated trienes useful for the diene-transmissive Diels—Alder reaction [106], and of exocyclic bis(allene)s and cyclobutene derivatives [107] have all been reported based on this method. 

Polyamino acids are easy to prepare by nucleophUe-initiated polymerisation of amino acid JV-carboxyanhydrides. Polymers such as poly-(L)-leucine act as robust catalysts for the epoxi-dation of a wide range of electron-poor alkenes, such as y-substituted a,Ji-unsaturated ketones. The optically active epoxides so formed may be transformed into heterocyclic compounds, polyhydroxylated materials and biologically active compounds such as dUtiazem and taxol side chain. 

Volume 64 of our series consists of six chapters covering an exciting range of topics in contemporary heterocyclic chemistry. M. TiSler and P. Kolar (Ljubljana, Slovenia) review applications of various amino acids in the synthesis of chiral heterocycles which have become of great importance as synthons for the preparation of a variety of optically active derivatives. 

An alternative way leading to optically active homoallylic alcohols involves the use of l,3-dioxan-4-ones 32. These heterocycles can be easily prepared, in good yield, from an aldehyde or ketone 6 and enantiomerically pure 3-hydroxybutanoic acid 94 (Scheme 13.13) [17]. 

Park, J.-I. Tian, G. R. Kim, D. H. Synthesis of optically active 2-alkyl-3,4-iminobutanoic acids. /J-Amino acids containing an aziridine heterocycle. /. Org. Chem. 2001, 66, 3696-3703. 

Any kind of C-Mannich base has been actually allowed to react with a variety of amines, including aminoalcohols and amino acids. Cyclic amines, - including optically active derivatives, - and amides arc also employed as are a number of aromatic heterocycles. 

The acid-catalysed intramolecular 1,5-nucleophilic O-heterocyclization of (p -dienyl)tricarbonyliron diols (82) occurs with 1,2-migration of the side chain. This cyclization has been shown to be a key stereoselective step towards racemic and optically active conformationally locked phosphocholins (83) and (84) as potential anticancer agents (Scheme 12). ... 

In the presence of a chiral dibasic acid, photocylisation of the unsaturated acylanilide yields an optically active phenanthridone the optical yield can be as high as 42% (T. Naito, Y. Tada and I. Ninomiya, Heterocycles, 1984. 22, 237). 

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