The mechanism of concerted cycloadditions - a philosophical challenge of scientific explanation

1. The mechanism of concerted cycloadditions - a philosophical challenge of scientific explanation Sengen SunDiscovery Partners International, Inc.9640 Towne Centre Drive San Diego, California 92121

2. Chemical reactions are about migrations of nuclei and electrons - A self evident philosophical thinking. • Experimental results tell how nuclei migrate. • Chemists use arrows or semi arrows to indicate electron • migration for understanding. Chemical reaction mechanism: where comes the electron resource and where does it go in the bond formation and breaking?

3. Pattern and explanation in chemistry 1. A pattern is a collection of phenomena. Pattern is more related to migrations of nuclei. 2. Explanation is an understanding of phenomena. Explanation is more based on electron migration. Electron migration plays a deciding role in the nuclear migration and is the essence of chemical reaction mechanism.

4. Concerted cycloadditions (CCs) • They are highly useful reactions in the • formation of ring structures. • 2. They are specially interesting, stimulating, • and obfuscating.

5. Patterns in CCs Alder’s rules on Diels-Alder reactions: 1. The reactivity of a Diels-Alder reaction is increased when the electron-donating ability of a substituent(s) on the diene is increased and/or the electron-accepting ability of a substituent(s) on the dienophile is increased. 2. Diels-Alder reactions are endo-selective. 3. Diels-Alder reactions are cis-oriented. See: J. Sauer. Angew Chem Int Ed 6: 16-33, 1967.

6. Frontier molecular orbital theory • Chemical reactivity is decided by the smaller • HOMO-LUMO energy gap between two reactants. • 1. It was founded on Alder’s rules – empirical rules. • 2. It is more an empirical pattern than an explaining theory. • 3. It is a quantitative empirical rule? • 4. It has no generality. • (M. J. S. Dewar.A critique of frontier orbital theory. • THEOCHEM 200: 301-323, 1989. ).

7. Explanation of CCs was a blank for ~70 years! Both of Alder’s rules and FMO theory are about the same pattern concerning outcomes of nuclear rearrangements in the 3-D space based on the characteristics of reactants. They are not an equivalence to an explanation. They have to be explained for understanding.

8. A law in chemists’ minds - the Coulombic law on electrostatic forces When this law is applied in chemical reactions: A negatively charged center attacks positively charged one. Or a positively charged center attacks negatively charged one. Or “aligning regions of charge concentration with regions of charge depletion” (Bader & MacDougall: J. Am. Chem. Soc. 1985, 107, 6788).

9. Do some CCs violate Coulombic Law?

10. Are there two cases of reactions? “The one was the frontier-controlled case in which the reaction was controlled by the particular orbital interaction, and the other was the charge-controlled case, where it was controlled by electrostatic interaction of charges.” K. Fukui, Science, 1982, 218, 747-218

11. Philosophical analyses of orbitals • Recent related analyses of orbitals: • Bader et al. Angew.Chem. Int. Ed. Engl.1994, 33, 620-631 • Bader, Int. J. Quant. Chem.2003, 94, 173-177. • Gillespie & Popelier, From Lewis to Electron Densities … • Ogilvie, J. Chem. Ed. 1990, 67, 280-289. • Scerri, J. Chem. Ed. 2000, 77, 1492-1494. • Scerri, Philosophy of Science2001, 68 (Proceedings)S76-S88

12. But continuesthe excessive use of orbitals 1. Orbital Interactions and Their Effects on 13C NMR Chemical Shifts for 4,6-Disubstituted-2,2-dimethyl-1,3-dioxanes. J. Phys. Chem. A.;(Article); 2005; 2. Phase Coherent Electronics: A Molecular Switch Based on Quantum Interference. JACS 2002, 124, 4200. 3. The Role of Orbital Interactions in Determining the Interlayer Spacing in Graphite Slabs. JACS 2000. 4. Sulfur-Gold Orbital Interactions which Determine the Structure of Alkanethiolate/Au(111) Self-Assembled Monolayer Systems J. Phys. Chem. B. ; 2002; 106(49); 12727-12736

13. Quantum Reality? And easy understanding? Murray Gell-Mann has described quantum mechanics as 'that mysterious, confusing discipline which none of us really understands but which we know how to use'. Richard Feynman: “I think I can safely say that no-one understands quantum mechanics… Do not keep asking yourself, if you can possibly avoid it, …”

14. Biradical intermediate theoryby Firestone & Dewar Dewar JACS1984, 106, 209-219. “Multibond reactions cannot normally be synchronous”

15. Exploring electronic migration for understanding • Need theoretical evidence how electrons migrate in CCs: • Electron (or charge) densities are the only appropriate indicator. • Changes of orbitals of whatever kinds are irrelevant. • There is no information of the electron flow along the minimum • energy path (or IRC) of CCs.

16. IRC approach leads to confusion 1. Karadakov, et al. J Phys Chem A 105: 10946-10946, 2001. 2. Nguyen, et al. J Phys Chem A 105: 10943-10945, 2001. 3. Harcourt, et al. J Phys Chem A 105: 10947-10948, 2001. 4. K. Sakata.Electron Reorganization along the Intrinsic Reaction Coordinate in 1,3-Dipolar Cycloaddition. J Phys Chem A 104: 10001-10008, 2000.

17. Arbitrary collisions may reveal some valuable information

18. Electron transfer

19. Electron densities in arbitrary collisions manifest the electron flow S. Sun, Chemistry Preprint Archive, 2001, issue 7, 199-208 S. Sun, Chemistry Preprint Archive, 2002, , issue 1, 49-56

20. Electron-electron repulsion: the key factor to the easiness of electron flow B3LYP/6-31G* • Conjugation Hindrances: • Heteroatomic hindrance • Interruption of a conjugate system.

21. 1,3-Dipolar cycloadditions

22. The parent Diels-Alder reaction A collision between two reactants creates two spots of more positive Columbic potential at the two bond forming locations, a consequence of the force field overlapping of the carbon nuclei at the two pairs of reaction centers. Four of the six pi electrons are relocated to occupy these two spots to form two new sigma bonds.

23. Conclusions – part 1 1. Based on computational studies, I have discovered an electron migration mechanism of CCs that has never been documented in the literature. 2. For the first time in more than 70 years after the discovery of D-A Reactions, the electronic mechanism can be systematically explained based on concerted electron-donor and acceptor relationship at the 2 bond-forming locations. 3. Chemical reactivity is fundamentally decided by the easiness of electronic migration, - an evident philosophical point.

24. Conclusions – part 2 4. For the first time, it is discovered that electron-rich oxygen polarizes C=C bond by pushing away electron density to drive the cyclic electron flow in CCs. 5. It is discovered that the nucleophilicity or electrophicility of a reaction center depends on a particular dynamic reaction environment. 6. Demonstrated solid examples that computational chemistry is useful in the understanding of chemical phenomena that cannot be understood otherwise.

25. Conclusions –part 3 7. Orbitals cannot be understood beyond a mathematical tool. And the IRC approach covers up the information of electron flow in CCs. 8. All natural puzzles are easy ones once you solve them. In the other words, good science can be easily understood. 9. A call to experts in the related fields to evaluate the claims I made: reject them or confirm them!