Organic Chemistry III
Classroom: Rm 121
Time: M-3,4 and T-1,2
教授: Tien-Yau Luh 陸天堯
Rm 621
Tel. 4088
tyluh@ntu.edu.tw
助教: Jiun-Le Shih 施俊樂
Rm 617
Tel. 4087
shihjiunle@ntu.edu.tw
課程網址: http://www.ch.ntu.edu.tw/~tyluh/course/course97/index.html
Syllabus
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Introduction
Stereochemistry and Conformational
Analysis
Pericyclic Reactions and Woodward
Hoffmann Rule
Frontier Molecular Orbital Theory
Linear Free Energy Relationship and
Kinetic Isotope Effect
Retrosynthetic Approaches and Selected
Examples on Total Synthesis
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Reference books
Eric V. Anslyn and Dennis A. Dougherty “Modern Physical Organic
Chemistry”, University Science Books, 2006.
Francis A. Carey and Richard J. Sundberg “Advanced Organic
Chemistry” Parts A and B, 4th Ed., Kluwer/Plenum, 2000.
Michael B. Smith and Jerry March “Advanced Organic Chemistry”
5th Ed., Wiley, 2001
Robert B. Grossman “The Art of Writing Reasonable Organic
Reaction Mechanisms”, 2nd Ed., Springer, 2003
Stuart Warren “Organic Synthesis: The Disconnection Approach”
Wiley, 1984.
Book for fun
Alex Nickon and Ernest F. Silversmith “Organic Chemistry: the
Name Game”, Pergamon, 1987
Chapter 1 Introduction
• What can an organic chemist do?-representative examples
• Milestones of organic chemistry
• Equilibrium and Thermodynamics--a brief
review
• Reaction Kinetics--a brief review
• Chemists invent molecules.
• Biologists apply molecules.
• Physicists study molecules.
• Engineers fabricate molecules.
• Public enjoys molecules.
Luh, T.-Y. 2005
O
O
O
(Cy3P)(Im)RuCl2=CHPh
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O2N
NO2
OH
O
NO2
O2N
O
N
O2N
N
NO2
N
N
O
O2N
NO2
N
N
O2N
N
O2N
O2N
O2N
O2N
NO2
N
NO2
N
N
NO2
O
O
O
O
NO2
O
O2N
O
O
O2N
NO2
O
O2N
O
O
O2N
NO2
NO2
O
O
N
O
O
N
O
O
O
O
O
N
N
O
Cf.
N
h
N
h'
N
N
White, T. J.; Tabiryan, N. V.; Serak, S. V.; Hrozhyk, U. A.; Tondiglia, V. P.; Koerner, H.; Vaiaa R. A.; Bunning, T. J. Soft Matter
2008, 4, 1796.
Morimoto M.; Irie, M. Chem. Commun. 2005, 3895.
Lessard, I. A. D.; Walsh, C. T. Proc. Nat. Acad. Sci. USA 1999, 96, 11028.
Spencer, D. M.; Wandless, T. J.; Schreiber, S. L.; G. R. Crabtree, Science 1993, 262, 1019.
Glatthar, R.; Spichty, M.; Gugger, A.; Batra, R.; Damm, W.; Mohr, M.; Zipseb, H.; Giese, B. Tetrahedron 2000, 56, 4117.
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Cf.
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Kar, M.; Basak, A. Chem. Rev. 2007, 107, 2861.
Kar, M.; Basak, A. Chem. Rev. 2007, 107, 2861.
Dervan, P. B. Biorg. Med. Chem. 2001, 2215.
Behav. Ecol. Sociobiol. doi:10.1007/s00265-008-0620-6 (2008). Nature 2008, 454, 920.
• Organic Chemistry just now is enough to drive one
mad. It gives me the impression of a primeval
tropical forest, full of the most remarkable things; a
monstrous and boundless thicket, with no way of
escape, into which one may well dread to enter.
F. Wöhler, 1835
• Dissymmetry is the only and distinct boundary
between biological and nonbiological chemistry.
Symmetrical physical or chemical force cannot
generate molecular dissymmetry.
Louis Pasteur, 1851
• The structure known, but not yet accessible by synthesis, is to
the chemists what the unclimbed mountain, the unchartered
sea, the untilled field, the unreached planet, are to other men.
R.B. Woodward, 1965
• When we have faced with a problem of effecting a chemical
synthesis we have sought known methods. We have not
paused to think why we do not invent a new method every time.
If we adopt this philosophy we are going to be extremely busy
till the end of the century (2000) (a) trying to equal the enzymes,
and (b) thinking of new ways of synthesis.
Derek H. R. Barton, 1969
• This notion (by Pasteur) is no longer true. The recent
revolutionary development in asymmetric catalysis has totally
changed the approach to chemical synthesis.
Ryoji Noyori, 2001
If a definitive history of twentieth
century science is ever written,
one of the highlights may well be a
chapter on the chemical synthesis
of complex molecules.
Elias J. Corey, 1990
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2005 Yves Chauvin, Robert H. Grubbs,
Richard R. Schrock
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1965 Robert B Woodward
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1963 Karl Ziegler, Giulin Natta
2001 Williams S. Knowles, Ryoji
Noyori, K. Barry Sharpless
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1961 Melvin Calvin
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2000 Alan Heeger, Alan G.
MacDiamid, Hideki Shirakawa
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1957 Alexander R. Todd
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1953 Hermann Staudinger
1996 Robert F. Curl, Jr., Harold W.
Kroto, Richard E. Smalley
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1950 Otto Diels, Kurt Alder
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1947 Robert Robinson
1994 George A. Olah
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1990 Elias J. Corey
1938 Adolf Butenandt, Leopold
Ruzicka
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1987 Donald J. Cram, Jean-Marie
Lehn, Charles J. Pedersen
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1938 Richard Kuhn
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1937 Norman Haworth, Paul Karrer
1984 Bruce Merrifield
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1930 Hans Fischer
1983 Henry Taube
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1928 Adolf Windaus
1981 Kenichi Fukui, Roald Hoffmann
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1927 Heinrich Wieland
1979 Herbert C. Brown, Georg. Wittig
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1915 Richard Wilstaetter
1976 William Lipscomb
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1913 Alfred Werner
1975 John Cornforth, Vladimir Prelog
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1912 Victor Grignard, Paul Sabatier
1973 Ernst O. Fischer Geoffrey
Wilkinson
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1910 Otto Wallach
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1969 Derek Barton, Odd Hassel
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1905 Adolf von Baeyer
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1902 Emil Fischer
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Equilibria: Two typical cases
1.
A
K
K=
B
K = equilibrium constant
[ ] = concentration in mol L-1
2. A +B
K
C+D
[B]
[A]
K=
=
[products]
[reactants]
[C][D]
[A][B]
If K large: reaction “complete,” “to the right,” “downhill.”
How do we quantify?
Gibbs free energy, ∆G°
Gibbs Free Energy, ∆G°
∆G° = -RT lnK = -2.3 RT logK = -1.36logK
T in kelvins, K (zero kelvin = -273 °C)
R = gas constant ~ 2cal deg-1 mol-1
Large K : Large negative ∆G° : downhill
Equilibria and Free Energy
At 25ºC (298°K): ΔGº = - 1.36 logK
Enthalpy ∆H° and Entropy ∆S°
∆G° = ∆H° - T∆S°
Kcal mol-1
cal-1 deg-1 mol-1 or entropy units,
or e.u.
Enthalpy ∆H° = heat of the reaction; for
us, mainly due to changes in bond
strengths:
∆H° = (Sum of strength of bonds
broken)
– (sum of strengths of bonds
made)
Bond energies (Kcal/mol)
H H
104
C C
83
O O
35
H C
99
C C
147
O O
119
H N
93
C C
201
N N
41
H O
88
C N
73
N N
226
H F
135
C O
86
F
F
37
H Cl
103
C S
65
Cl
Cl
58
H Br
87
C
F
117
Br
Br
46
71
C Cl
H
I
C Br
C
I
79
69
52
I
I
36
Example:
CH3CH2―H
101
+
Cl―Cl
58
CH3CH2―Cl + H―Cl
84
103
∆H° = 159 – 187 = -28 kcalmol-1
∆H° negative: called “exothermic”
if positive: called “endothermic”
∆S° = change in the “order” of the
system. Nature strives for disorder.
More disorder = positive ∆S ° (makes
a negative contribution to ∆G° )
Chemical example:
CH2 CH2 + HCl
2 molecules
CH3CH2Cl
1 molecule
∆H° = -15.5 kcal mol-1
∆S° = -31.3 e.u.
If # of molecules unchanged,
∆S° small, ∆H° controls ( we
can estimate value from bond
strength tables)
Kinetics
• Rate law and reaction mechanisms
A steady state approach
Example: SN1 reaction
JACS 1966, 88, 2599.
Hammond Postulate
“Early TS”
“Late TS”
Curtin-Hammett Principle
Kinetic vs thermodynamic control
Intramolecular vs Intermolecular Reactions
Intramolecular versus intermolecular reactions benefit from a far more favorable
entropy of activation
In forming small rings, ring strain developing in the product decelerates the rate
of reaction (large enthalpy of activation) that can offset the favorable entropy of
activation rate acceleration.
Geminal dimethyl effect
(Thorpe Ingold effect)