Applications of planar-chiral heterocycles in asymmetric catalysis

Abstract

The development of planar-chiral heterocycles for asymmetric catalysis and their applications to enantioselective processes were investigated. Reactions including the kinetic resolution of propargylic alcohols, the enantioselective ring opening of meso epoxides, and the asymmetric hydrosilylation of ketones were studied. ... During the past few years, our group has developed lb as one of the most effective and versatile nonenzymatic acylation catalysts for the kinetic resolution of arylalkylcarbinols. Surprisingly, however, when the optimized reaction conditions were applied to the kinetic resolution of secondary propargylic alcohols, only low to moderate selectivity factors were obtained. Detailed investigations revealed that triethylamine serves as a competitive general base catalyst in the acylation reaction of propargylic alcohols, thereby suppressing the intrinsic selectivity factor. When base is omitted, the selectivity factor for propargylic alcohol 2 (R1 = Ph, R2= Me) increases from 6 to 20. Using this new protocol, we can effect the kinetic resolution of a number of propargylic alcohols with selectivity factors of 10 or above. ... Catalysts in which oxygen is the nucleophilic site effect a number of useful transformations. In view of the utility of planar-chiral pyridine derivatives such as 1, it occurred to us that pyridine N-oxides 3 might also prove to be effective asymmetric catalysts. We synthesized complexes 3a-c and were gratified to discover that 3a efficiently catalyzes the ring opening of cis-stilbene oxide by SiC14, albeit in modest enantiomeric excess.

(cont.) By increasing the steric demand of the bottom ring, we found that the selectivity increases significantly. Thus, bulky derivative 3c affords 92% ee in the ring opening of cis-stilbene oxide at -85 C. A number of epoxides can be desymmetrized in very good yield and high stereoselectivity under these conditions (up to 98% ee). ... In addition, we have also synthesized a new family of planar-chiral N,P-ligands (4). The ligand design allows incorporation of different substituents on the phosphorus atom and on the C5R5 bottom ring, thereby providing a means for tuning catalyst enantioselectivity. We chose the asymmetric hydrosilylation of ketones to test the effectiveness of our ligand design. In general, sterically demanding silanes such as MesPhSiH2 and (o-tol)2SiH2 furnish better enantioselectivities than simple silanes like Ph2SiH2. Among the planar-chiral ligands tested, we found that ligand 4a gives the best yields and enantioselectivities for a wide array of substrates (arylalkyl ketones: up to 99% ee; dialkyl ketones: up to 96% ee). Deuterated benzaldehyde-l-d can also be reduced with excellent enantioselectivity (95% ee). Access to chiral silanes is also possible using the same ligand.