Bifunctional catalysis, natural products

The development of highly efficient asymmetric catalysts is one of the most intensively investigated research fields today.1 Catalytic asymmetric reactions are extremely powerful in terms of the practicality and atom economy.2 The power of asymmetric catalysis is rapidly growing, so as to be applicable to syntheses of natural products with complex structures. We call total syntheses using catalytic asymmetric reactions in key steps catalytic asymmetric total syntheses . In this chapter, we describe our recent success in catalytic asymmetric total syntheses of (-)-strychnine and fostriecin. Both of the total syntheses involve catalytic asymmetric carbon-carbon bond forming reactions using bifunctional catalysts developed in our group3 as key steps. 

Despite the relative high number of ACTCs that have been employed in asymmetric catalysis, there has been no application of these catalysts for the construction of intermediates of interest for natural product synthesis. Cr(CO)3-complexed ligands that have been described for such purposes lack an element of planar chirality. Thus, the importance of the chromium(0)-moiety relies on the creation of a suitable electronic and/or steric environment within the active structure of the catalyst. Natural products that have been synthesized by such route include (i )-(-)-rhododendrol, the aglycone of rhododendrin, a hepato-protective agent, the macrolides (i )-(-)-phorcantholide I and (i )-(-i-)-lasiodi-polin and related bifunctional synthons [49-53], Scheme 13. 

This collection begins with a series of three procedures illustrating important new methods for preparation of enantiomerically pure substances via asymmetric catalysis. The preparation of 3-[(1S)-1,2-DIHYDROXYETHYL]-1,5-DIHYDRO-3H-2.4-BENZODIOXEPINE describes, in detail, the use of dihydroquinidine 9-0-(9 -phenanthryl) ether as a chiral ligand in the asymmetric dihydroxylation reaction which is broadly applicable for the preparation of chiral dlols from monosubstituted olefins. The product, an acetal of (S)-glyceralcfehyde, is itself a potentially valuable synthetic intermediate. The assembly of a chiral rhodium catalyst from methyl 2-pyrrolidone 5(R)-carboxylate and its use in the intramolecular asymmetric cyclopropanation of an allyl diazoacetate is illustrated in the preparation of (1R.5S)-()-6,6-DIMETHYL-3-OXABICYCLO[3.1. OJHEXAN-2-ONE. Another important general method for asymmetric synthesis involves the desymmetrization of bifunctional meso compounds as is described for the enantioselective enzymatic hydrolysis of cis-3,5-diacetoxycyclopentene to (1R,4S)-(+)-4-HYDROXY-2-CYCLOPENTENYL ACETATE. This intermediate is especially valuable as a precursor of both antipodes (4R) (+)- and (4S)-(-)-tert-BUTYLDIMETHYLSILOXY-2-CYCLOPENTEN-1-ONE, important intermediates in the synthesis of enantiomerically pure prostanoid derivatives and other classes of natural substances, whose preparation is detailed in accompanying procedures. 

---