Development of catalytic asymmetric carbon-carbon bond forming reactions: Applications in organic synthesis.

摘要

Chapter 1. The Zr-catalyzed diastereo- and enantioselective carbomagnesation of cyclic ethers with higher alkyls of magnesium was investigated.*; Chapter 2. The first enantioselective total synthesis of antifungal agent Sch 38516 was achieved. Highlights of the total synthesis include the following: (1) Zr-catalyzed regio-, diastereo-, and enantioselective carbomagnesations to efficiently establish the stereochemistry of intermediates 1 and 2. (2) Diastereoselective [3 + 2] cycloaddition, en route to the synthesis of the natural product carbohydrate moiety, to provide 4. (3) Diastereoselective and efficient glycosidation of the acyclic diene 3. (4) Catalytic ring closing metathesis of the highly functionalized 5 to afford macrocyclic lactam 7 with Schrock's Mo complex 6.*; Chapter 3. The first enantioselective total synthesis of the antihypertensive agent (S,R,R,R)-nebivolol was accomplished. Zr-catalyzed carbomagnesation and Mo-catalyzed metathesis play a pivotal role in a convergent approach to the target molecule. In addition, a stereo- and regioselective Pd-catalyzed allylic epoxide ring opening to establish relative syn 1,2 stereochemistry was developed. Also noteworthy was the efficient use of a Wacker oxidation and a Norrish type II photochemical cleavage.*; Chapter 4. The application of Mo-catalyzed asymmetric ring-closing metathesis for the synthesis of optically pure chromenes was investigated.*; *Please refer to dissertation for diagrams.