Chiral ligands, bifunctional

Asymmetric transfer hydrogenation of imines catalyzed by chiral arene-Ru complexes achieves high enantioselectivity (Figure 1.34). Formic acid in aprotic dipolar solvent should be used as a hydride source. The reaction proceeds through the metal-ligand bifunctional mechanism as shown in the carbonyl reduction (Figure 1.24). 

A chiral Ru hydride 23 is formed and it is assumed that the hydrogen transfer occurs via metal-ligand bifunctional catalysis. The N-H linkage may stabilize a transition state 24 by formation of a hydrogen bond to the nitrogen atom. Stereochemistry is determined by formal discrimination of the enantiofaces at the sp2 nitrogen atom of the cyclic imine. 

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. 

A much higher and more efficient chiral version (>90%) of the cyclopropanation of allylic alcohols is obtained by using the amphoteric bifunctional ligand (R,R)-93 prepared from commercially available (+)-(/ ,7 )-At,TV,A, A -tetramethyltartaric acid diamide and butyl-boronic acid. The dioxyborolane chiral ligand proved to be extremely effective with several types of substituted allylic alcohols 92. The chiral ligand 93 can easily be removed and recovered (> 80%) by a simple aqueous extraction of the organic layer after the reaction. 

The great versatility of binol as a chiral ligand has been extended to the Strecker reaction. Shibasaki38 has developed bifunctional catalysts employing the use of this species. After the reportewd use of an aluminum variation of this catalyst 75 for the asymmetric formation of cyanohydrins, aluminum and gadolinium derivatives of 78 were shown to efficiently catalyze the addition of cyanide to imines. 

Other chiral diamine-( -arene)ruthenium catalysts were developed by Noyori where the chirality was centred at the metal (see Figure 3.18). These complexes were effective catalysts for asymmetric transfer hydrogenation of carbonyl compounds and a mechanism involving a metal-ligand bifunctional process was proposed. 

Finally in Chapters 11-13, some of the more recent discoveries that have led to a renaissance in the field of organocatalysis are described. Included in this section are the development of chiral Brdnsted acids and Lewis acidic metals bearing the conjugate base of the Bronsted acids as the ligands and the chiral bifunctional acid-base catalysts. 

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