The mechanism of concerted

cycloadditions - a philosophical
challenge of scientific explanation
 
Sengen Sun
Discovery Partners International, Inc.
9640 Towne Centre Drive
San Diego, California 92121

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 Chemical reactions are about
migrations of nuclei and electrons
- A self evident philosophical thinking.

1. Experimental results tell how nuclei migrate.

2. 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?

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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.
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 Concerted cycloadditions (CCs)

1. They are highly useful reactions in the

formation of ring structures.

2. They are specially interesting, stimulating,

and obfuscating.

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 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.

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 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. ).
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 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.

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 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).

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Do some CCs violate Coulombic Law?
O O
   
O  O ' O O
X  + '
   
3 1 2

O O
O

O
X + -
O N N O N

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 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
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 Philosophical analyses of orbitals
Recent related analyses of orbitals:

1. Bader et al. Angew. Chem. Int. Ed. Engl. 1994, 33, 620-631

2. Bader, Int. J. Quant. Chem. 2003, 94, 173-177.

3. Gillespie & Popelier, From Lewis to Electron Densities …

4. Ogilvie, J. Chem. Ed. 1990, 67, 280-289.

5. Scerri, J. Chem. Ed. 2000, 77, 1492-1494.

6. Scerri, Philosophy of Science 2001, 68 (Proceedings)S76-S88

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 But continues
the 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

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 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, …”

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 Biradical intermediate theory
by Firestone & Dewar
Dewar JACS 1984, 106, 209-219.
“Multibond reactions cannot normally be synchronous”
O O
   
O O ?
+ O
    O
1 2

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 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.

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IRC approach leads to confusion

+ - + - + -
N O N O N O

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. 16
Arbitrary collisions may reveal some
valuable information

O
O
O O

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 H 0.183
-0.287 O-0.398 -CH2 +0.056
0.160 H 

-0.131 0.226
0.141 H H 0.108
-CH2 -0.032
-0.440
O 0.181 H 0.162
0.228 H 0.138 -0.429
0.203 H 0.11 0.165 -0.332 O
H H
-0.083
5 H -0.292
0.172 -0.065 0.246
H -0.343 H 0.148 -0.119 2.10 Å
0.172H 2.10 Å 0.224 H H
-0.343 O-0.440
H O 0.139 0.101
0.148 -0.400
0.203H
-0.083 0.228
H 0.134
H
0.040
H Electron transfer
0.148 0.115
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Electron densities in arbitrary collisions
manifest the electron flow
O O

O O

S. Sun, Chemistry Preprint Archive, 2001, issue 7, 199-208

S. Sun, Chemistry Preprint Archive, 2002, , issue 1, 49-56

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 Electron-electron repulsion: the key
factor to the easiness of electron flow
O O

2.467 Å 1.890 Å 2.223 Å 1.920 Å

O O
B3LYP/6-31G*

Conjugation Hindrances:
1. Heteroatomic hindrance
2. Interruption of a conjugate system.

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 1,3-Dipolar cycloadditions

O
+ -
N O N

O O
O

O
X + -
O N N O N

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 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.

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 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.

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 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.

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 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!

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