Enantioselective synthesis building blocks

The synthesis of chiral dendrimers from various building blocks, their - difficult - structure determinations, and their - potential - use in physiological applications, in bioassays, and in enantioselective catalysis are reviewed. 

Two interesting yeast carbonyl reductases, one from Candida magnoliae (CMCR) [33,54] and the other from Sporobolomyces salmonicolor (SSCR) [55], were found to catalyze the reduction of ethyl 4-chloro-3-oxobutanoate to give ethyl (5)-4-chloro-3-hydroxybutanoate, a useful chiral building block. In an effort to search for carbonyl reductases with anti-Prelog enantioselectivity, the activity and enantioselectivity of CMCR and SSCR have been evaluated toward the reduction of various ketones, including a- and /3-ketoesters, and their application potential in the synthesis of pharmaceutically important chiral alcohol intermediates have been explored [56-58]. 

Enantiomerically pure amines are extremely important building blocks for biologically active molecules, and whilst numerous methods are available for their preparation, the catalytic enantioselective hydrogenation of a C=N bond potentially offers a cheap and industrially viable process. The multi-ton synthesis of (S)-metolachlor fully demonstrates this [108]. Although phospholane-based ligands have not proven to be the ligands of choice for this substrate class, several examples of their effective use have been reported. 

In recent years, much effort has been devoted to the enantioselective hydrogenation of yS-ketoesters, essentially using ruthenium-based catalysts. The aim of these reactions is to produce selectively enantiopure syn diols which are the key building blocks for the synthesis of inhibitors of HMG-coenzyme A reductase. Due to the availability of the AMPP ligands, and the reactivity of the rhodium catalysts based on them (notably the alkyl-substituted ones) towards ketonic sub-... 

Many methods have been reported for the enantioselective synthesis of the remaining PG building block, the (J )-4-hydroxy-cyclopent-2-enone. For example, the racemate can be kinetically resolved as shown in Scheme 7-28. (iS )-BINAP-Ru(II) dicarboxylate complex 93 is an excellent catalyst for the enantioselective kinetic resolution of the racemic hydroxy enone (an allylic alcohol). By controlling the reaction conditions, the C C double bond in one enantiomer, the (S )-isomer, will be prone to hydrogenation, leaving the slow reacting enantiomer intact and thus accomplishing the kinetic resolution.20... 

Miyafuji and Katsuki95 reported the desymmetrization of meso-tetrahydrofuran derivatives via highly enantioselective C-H oxidation using Mn-salen catalysts. The optically active product lactols (up to 90% ee) are useful chiral building blocks for organic synthesis (Scheme 8-48). 

Tietze, L.F. and Gorlitzer, J., Preparation of chiral building blocks for a highly convergent vitamin E synthesis. Systematic investigations on the enantioselectivity of the Sharpless bishydroxilation. Synthesis, 1998, 873. 

Baeza, A., Casa, J., Najera, C., Sansano, J.M. and Saa, J.M., Enantioselective synthesis of O-methoxycarbonyl cyanohydrins chiral building blocks generated by bifunctional catalysis with BINOLAM-AICI. Eur. J. Org. Chem., 2006, 1949. 

Optically active epoxides are important building blocks in asymmetric synthesis of natural products and biologically active compounds. Therefore, enantio-selective epoxidation of olefins has been a subject of intensive research in the last years. The Sharpless [56] and Jacobsen [129] epoxidations are, to date, the most efficient metal-catalyzed asymmetric oxidation of olefins with broad synthetic scope. Oxidative enzymes have also been successfully utilized for the synthesis of optically active epoxides. Among the peroxidases, only CPO accepts a broad spectrum of olefinic substrates for enantioselective epoxidation (Eq. 6), as shown in Table 8. 

Enantiomerically pure sulfoxides play an important role in asymmetric synthesis either as chiral building blocks or stereodirecting groups [156]. In the last years, metal- and enzyme-catalyzed asymmetric sulfoxidations have been developed for the preparation of optically active sulfoxides. Among the metal-catalyzed processes, the Kagan sulfoxidation [157] is the most efficient, in which the sulfide is enantioselectively oxidized by Ti(OzPr)4/tBuOOH in the presence of tartrate as chirality source. However, only alkyl aryl sulfides may be oxidized by this system in high enantiomeric excesses, and poor enantioselectivities were observed for dialkyl sulfides. 

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