| Summary: | 博士 === 國立中興大學 === 化學系所 === 97 === The purpose of the present investigations was to determine the catalytic activity of chiral ligands and reagents and utilize the methodologies in pharmaceutical and drug industries. Although, extensive investigations on asymmetric catalysis have been reported, but most of these systems are complicated. For instance, in chapter 1, a brief idea about chirality, asymmetric catalysis and their growing importance in pharmaceutical and drug industries was described.
In organic chemistry, conjugate addition was most widely useful method for carbon-carbon bond formation; as a result catalytic asymmetric addition of organozinc reagents to unsaturated carbonyl compounds represents one of important approach. In chapter 2, a new series of tridentate P,N,O ligands having hard and soft donor atoms derived from chiral amino alcohols were developed and employed in the Cu(II)-catalyzed conjugate addition of diethylzinc to substituted chalcones. The asymmetric additions to a variety of substituted chalcones afforded products in excellent yields with excellent enantioselectivities up to 97% ee.
Accordingly, the absence of efficient and highly enantioselective methods to prepare chiral tertiary alcohols is a long-standing problem for organic chemists. In chapter 3, part I, we report a novel asymmetric addition of vinyl group to ketones using vinylaluminum reagents catalyzed by in situ prepared Ti(OiPr)4 complexes of (S)-BINOL to afford diversified tertiary allylic alochols. Varieties of aromatic ketones bearing either an electron-donating or an electron-withdrawing substituent on aromatic ring were examined to afford products in excellent enantioselectivities up to 98% ee with high yields. A 10-fold scale-up reaction afforded the product in a similar yield with a comparable enantioselectivity. More importantly, additions of a variety of vinyl reagents including functionalized vinyls were demonstrated, affording tertiary allylic alcohols with good to excellent enantioselectivities up to 96% ee.
Finally, (S)-tiemonium iodide, a tertiary thienyl alcohol, is well known for its biological activity as well as key sub-structures in bioactive compounds and pharmaceuticals. Therefore, in chapter 3, part II, a novel direct asymmetric catalytic thienylaluminum addition to ketones catalyzed by in situ-prepared Ti(OiPr)4 complexes of (S)-BINOL and (R)-BINOL was described. The results showed that the catalytic system worked excellently for aromatic ketones including either an electron-donating or an electron-withdrawing substituent to afford up to 97% ee with high yields. Importantly, a concise synthesis of (S)-tiemonium iodide using this methodology from the commercially available benzene and 3-bromopropionyl chloride in 4 steps.
|
|---|
