1. Chemistry 125: Lecture 34 Sharpless Oxidation Catalysts and the Conformation of Cycloalkanes Professor Barry Sharpless of Scripps Research Institute describes his Nobel- prizewinning development of titanium-based catalysts for stereoselective oxidation, the mechanism of their reactions, and their use in preparing esomeprazole. Conformational energy of cyclic alkanes illustrates the use of molecular mechanics. Synchronize when the speaker finishes saying “Remember what the point of this synthesis was?” Synchrony can be adjusted by using the pause(||) and run(>) controls. For copyright notice see final page of this file

2. RO ~ racemic OR O OEt O O CO 2 Et Ti RO O 3) Chiral Catalysis by Titanium/Diethyltartrate Ti (etc) ROO RO + Ti O O O Ti (etc) OEt O CO 2 Et O RO Ti O O O Ti (etc) OEt O CO 2 Et 94% e.e. (3% R) with added iPr 2 NEt (discovered in 2000) n ** R S R' O Ti O O O Ti (etc) OEt O CO 2 Et + (for no obvious reason) catalytic cycle RO ROO S R R' Chiral “Oxidizing Agent” R S R' + O R S O R S Nobel Prize 2001

3. THE HUMAN UMBILICAL CORD

6. Michaelson and Oshima

7. Tsutomu Katsuki’s famous “recipe” Stanford Chemistry Department (1980)

11. Tsutomu Katsuki’s discovery -- a memorable day in 1980 at Stanford University!

14. "A man in California just won a Nobel Prize for mixing paint and wine!" Los Angeles Times, October, 2001

20. Stretch Bend Stretch-Bend Torsion Non-1,4-VDW 1,4-VDW TOTAL Cyclobutane Puckering (by Molecular Mechanics) Torsion vs. Bend Relaxed 0.77 16.07 -0.92 11.23 -0.26 2.35 29.24 Planar 0.66 13.48 -0.78 14.81 -0.28 2.27 30.16

21. Stretch Bend Stretch-Bend Torsion Non-1,4-VDW 1,4-VDW TOTAL Cyclopentane Puckering (by Molecular Mechanics) "Envelope" Relaxed 0.31 2.14 -0.09 6.38 -0.51 3.19 11.42 Planar 0.19 0.51 0.02 11.53 -0.48 4.34 16.10

22. e.g. What is the source of the barrier to c-hexane ring flip? two butane gauche  eclipsed (~7 kcal/mole) But why does the plastic model click? Baeyer Angle Strain +7° +5° -3° +5° Like a plastic model, molecular mechanics is satisfying because not only does it say what a structure should be, it can also say “why”.

23. Are They “True”? YES Are Molecular Mechanics Programs Useful? NO

24. End of Lecture 34 Dec. 3, 2008 Copyright © J. M. McBride 2009. Some rights reserved. Except for cited third-party materials, and frames 3-19 used by Prof. Sharpless, all content is licensed under a Creative Commons License (Attribution-NonCommercial-ShareAlike 3.0).Creative Commons License (Attribution-NonCommercial-ShareAlike 3.0) Use of this content constitutes your acceptance of the noted license and the terms and conditions of use. Materials from Wikimedia Commons are denoted by the symbol. Third party materials may be subject to additional intellectual property notices, information, or restrictions. The following attribution may be used when reusing material that is not identified as third-party content: J. M. McBride, Chem 125. License: Creative Commons BY-NC-SA 3.0