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Polar Effects in Radical Reactions
Partha Nandi
HHH
Department of ChemistryMichigan State University
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Objectives and Motivations
• Origin of polar effects in organic radical reactions
• Improve the ability to design experiments
• Find new ways to expand the scope of known reactionmechanisms to address reactivity-selectivity problems
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Outline• The polar-effect in traditional organic reaction mechanisms.
Is a polar-effect anticipated for radical reactions?
• Factors responsible for polar-effect in radicals
(1) Geometry and Orbital interactions (2) Non-perfect synchronization of TS(3) Solvent polarity and viscosity (“cage effect”)
• Specific examples and illustrations
• Conclusions and remarks
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Outline
• Polar-effects in traditional organic reaction mechanismsIs a polar-effect anticipated for radical reactions?
• Factors responsible for polar-effects in radicals
(1) Geometry and Orbital interaction effects(2) Non-perfect synchronization of TS(3) Solvent polarity and viscosity (“cage effect”)
• Specific examples and illustrations
• Conclusions and remarks
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Polar Effects in Stereo-type Organic Reaction Mechanisms?
I. SN1 Case II. SN2 case
R-X + Y(s)n
R (s)n
TS1TS2
R-Y + X(s)n
More polar solvent
Less polar solventR
R-X + Y(s)n
X RY
R-Y + X(s)n
More polar solvent
Less polar solvent
YX
Same notion works for E1 and E2 mechanism
“Theoretical and Physical Principles of Organic Reactivity”, Pross, A. John Wiley & Sons, Inc. 1996.
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Summary of the Solvent Polarity Effect
Large DecreaseAnnihilationY–+ R–X--> Y– δ…R…X+δ
Small DecreaseDispersionY– + R–X--> Y– δ…R…X–δ
Small DecreaseDispersionR–X+δ−−> R+δ…X–δ
Large IncreaseSeparationY+ R–X-->Y+ δ…R…X–δ
Large IncreaseSeparationR–X-->R+δ…X–δ
Effect of polarity increase on reaction rate
Nature of Charge Type
Reaction Type
“Theoretical and Physical Principles of Organic Reactivity”, Pross, A. John Wiley & Sons, Inc. 1996.
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Outline• Polar-effects in traditional organic reaction mechanisms a
brief overview. Is polar-effect anticipated for radical reactions
• Factors responsible for polar-effects in radicals
(1) Geometry and Orbital interaction effects(2) Non-perfect synchronization of TS(3) Solvent polarity and viscosity (“cage effect”)
• Specific examples and illustrations
• Conclusions and remarks
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Geometry and Orbital Polarization: Methyl Radical
H3 M.O C A.Os
2pz 2px 2py
MOs for Me
σ
π π
π∗ π∗
σ*
nb
(Not to scale)
E
“Theoretical and Physical Principles of Organic Reactivity”, Pross, A. John Wiley & Sons, Inc. 1996.
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Energy Changes on Pyramidalizations
• ESR coupling
• Computations
• MO picture
• Polarization proportionalto dipole moment
CF3
CHF2
CH3
CH2F
E
0 4 8 12
ω, degrees
C
ω=α−90
α
Zheng, X.; Phillips, D. L. J. Phys. Chem. A. 2000, 104, 1030.Cramer, C. J. J. Org. Chem., 1991, 56, 5229.
Rozum, I.; Tennyson, J. J. Phys. B. 2004, 37, 957.
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MO for Pyramidalization
C XX X
SOMO - filled lone pairs repulsion
pyramidalization helps to stabilize the SOMO
by the interaction of p-σ∗
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• Geometrical flexibility of radicals can be rationalized from MO.
• Vibrational polarizability
Vibrational Polarization & Pyramidalization
“Solvation of the Methyl radical and Its implication” Stratt, R. M.; Desjardins, S. G. J. Am. Chem. Soc. 1984, 106, 256.
Vibrational polarization turning onPyramidal inversion
E
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Role of Substituents on SOMO
X typeNR2, ORCl, Me, I
Z typeCOR, CN, SOR,NO, NO2
C typeC=CH2Ph, etc
E
n or filled σ
"C" centeredSOMO
π
π∗π∗
orbital
“Orbital Interaction Theory in Organic Chemistry’” 2001, 2nd Ed, Rauk, A. Wiley & sons. Inc.,
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Outline
•Polar-effects in traditional organic reaction mechanisms a brief overview. Is polar-effect anticipated for radical reactions?
• Factors responsible for polar-effects in radicals
(1) Geometry and Orbital interaction effects(2) Non-perfect synchronization of TS(3) Solvent polarity and viscosity (“cage effect”)
•Specific examples and illustrations
•Conclusions and remarks
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Hammond’s Postulate and Limitations• Hammond’s postulate - what does it tell us?
• Instant idea on nature of TS
• Fails to give an accurate location of TS
• Does not consider multiple degrees of freedomsalong the reaction coordinate
R
P
R'P'
E
RC
• Modern version and extension of Hammond’s postulate - “The Principle of Nonperfect Synchronization”
Bernasconi, C. F. Acc. Chem. Res. 1992, 25, 9.
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Nonperfect Synchronization• ------- hypothetical resonance developments synchronous with charge transfer
• ____ actual situation where resonance development lags behind charge transfer
• Smaller degree of resonance stabilization of TS leads to a higher barrier
“The Principle of Nonperfect Synchronization: More than a qualitative concept?”Bernasconi, C. F. Acc. Chem. Res. 1992, 25, 9.
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“Nonperfect Synchronization” & “Imperfect TS”
• Reaction potential energy surface is multi-dimensional
• Bond breaking and formation
• Solvation and desolvation
• Delocalization and localization of charge
• Unequal progress at the TS, termed as “Imperfect TS”
“The Principle of Nonperfect Synchronization: More than a qualitative concept ?” Bernasconi, C. F. Acc. Chem. Res. 1992, 25, 9.
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Outline• Polar-effects in traditional organic reaction mechanisms a
brief overview. Is polar-effect anticipated for radical reactions?
• Factors responsible for polar-effects in radicals
(1) Geometry and Orbital interaction effects(2) Non-perfect Synchronization of TS(3) Viscosity (“cage effect”) and solvent polarity
• Specific examples and illustrations
• Conclusions and remarks
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Viscosity EffectsFate of diffusive cage pair
( R/R )cage
R-R
R-H + R-H
kdisp
kdim
R + Rkdiff
k-diff
kdisp/ kdim
for t-Buradical
η (cP)0
5
5.5
6.5
1 2 3
for 2-Propyl radical
•Variation of kdisp/kdim with viscosity
•Shape matters: t-Bu radical an ellipsoid, isopropyl “V” shaped
•Similar trend observed for polar radicalreactions
Shuch, H. H.; Fischer, H. Helv. Chim. Acta 1978, 61, 2463.Minisci, F.; Vismara, E.; Fontana, F.; Morini, G.; Serravalle, M.; Giordano, C. J. Org. Chem. 1987, 52, 730.
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Polar Solvent Decelerating the Rate
N
O
CH2
+ N
O
Solvent
TEMPO
9.5 + 0.7Acetonitrile6.23 + 3Tetrahydrofuran5.17 + 2Chlorobenzene4.18 + 1Benzene3.41 ± 2Cyclohexane2.
50 + 1.5n-pentane1.
kT X 10-7, M-1 s-1SolventEntry
Beckwith, A. L. J.; Bowry, V. W.; Ingold, K. U J. Am. Chem. Soc. 1992, 114, 4983.
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Outline
• Polar-effects in traditional organic reaction mechanisms a brief overview. How do we think about radicals?
• Factors responsible for polar-effects in radicals
(1) Solvent polarity effects(2) Internal pressure and viscosity (“cage effect”)(3) Non-perfect synchronization of TS(4) Geometry and Orbital polarization
• Specific examples and illustrations
• Conclusions and remarks
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Early Examples of Polar Radical Reactions
+ Br2hv
CH2 H Brδ−δ+
Br
Kim, S. S.; Choi, S. Y.; Kang, C. H. J. Am. Chem. Soc. 1985, 107, 4234.
R CO
O O R C OO
OC(Me)3 R + CO2 + tBuOheat
Barlett, P. D.; Hiatt, R. R. J. Am. Chem. Soc. 1958, 80, 1398.
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Specific Examples and Illustrations
(1) NO catalyzed oxidations
(2) MGM, ICM and MCM catalyzed isomerizations
(3) Silyl enol ether mediated 5-exo and 6-endo cyclizations,and general approach to 4-allyl oxyl radical cyclizations
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Aerobic Oxidation of Benzyl Alcohols by NHPI or PINO
O2PhCH(OOH)OH
PhCH(OH)2PhCHO
N
O
O
O H-CHOHPh+ N
O
O
O H CHOHPh+– δ δ
N
O
O
O H-PhCHOH
PhCHOH PhCH(O)OH
-H2O
– OH
H atom abstraction
Minisci, F.; Punta, C.; Recupero, F.; Fontana, F.; Pedulli, G. F. J. Org. Chem. 2002, 67, 2671.Annunziatini, C.; Gerini, M. F.; Lanzalunga, O.; Lucarini, M. J. Org. Chem. 2004, 69, 3431.
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Structural Modifications in PINO
N
O
O
O
R1
R2
R3
HO+
HON
O
O
OH
R1
R2
R3
+
PINO NHPI
-0.54HMeOMeO5
-0.60HHMeO4
-0.68HHH3
-0.69HHF2
-0.70HMeOCOH1
ρR3R2R1Entry
Annunziatini, C.; Gerini, M. F.; Lanzalunga, O.; Lucarini, M. J. Org. Chem. 2004, 69, 3431.
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Electronic Perturbation & Implications
-0.4
-0.2
0.0
0.2
0.4
0.6
0.8
1.0
-0.9 -0.5 -0.1 0.3 0.7
p-OMe
p-Me
p-CN
m-NO2m-CN
m-Cl
m-OMe
p-Clm-Me
p-NO2
σ+
log(kx/kH)
OH
X
O
X
H
PINO
Hammet plot whereρ= – 0.69
Minisci, F.; Recupero, F.; Cecchetto, A.; Gambarotti, C.; Punta, C.; Faletti, R.; Paganelli, R.; Padulli, G. Eur. J. Org. Chem. 2004, 109.
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Barrier Height for H Atom Abstraction
N
O
O
O H-CHOHPh+ N
O
O
O H CHOHPh+– δ δ
N
O
O
O H-PhCHOH
664949(O=CH)2NO
928683(O=CH)N(CH3) O
927978(O=CH)NHO
115109103H2NO
CCSD (T)-ccpVDZ/B3LYP/6-311++G
B3LYP/6-311++G
B3LYP/6-31G (kJ mol-1)
>NO radical
Hermans, I.; Vereecken, P. A.; Jacobs, A.; Peters, J. Chem. Commun., 2004, 1140.
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Potential Energy Surface Topology
-40
-30
-20
-10
0
10
20
30
TS/Saddle point
Pre-reaction complex
Post reaction complex
>NO + CH3OOH
>NOH + CH3OO
Reaction Co-ordinateZPE corrected Energy( kJmol-1)
E
(O=CH)2NO
Hermans, I.; Vereecken, P. A.; Jacobs, A.; Peters, J. Chem. Commun., 2004, 1140.
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MO Picture for H Atom Abstraction
B B H-A
H-A
B H A
Energy (Not to scale)B-H
B-H A
A
“The stability of alkyl radicals”, Tsang, W. J. Am. Chem. Soc., 1985, 107, 2872.“Kinetics and Thermochemistry of CH3, C2H5, i-C3H7, Study of equilibrium of R + HBr”Russel, J. J.; Seetula, J. A.; Gutman, D. J. Am. Chem. Soc., 1990, 112, 1347.
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Enthalpy Effect
N
OH
N
O
OHN
O
O
OH
O-H Bond Dissociation Energy (kcal/mol)
79.2 88.169.6
Minisci, F.; Recupero, F.; Cecchetto, A.; Gambarotti, C.; Punta, C.; Faletti, R.;Paganelli, R.; Padulli, G. Eur. J. Org. Chem. 2004, 109-119.
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Fundamental Steps of TEMPO CatalyzedOxidations
RN
RO
RN
RO R O O R O O
R H + O X R HOX+
NO
R
NOR
NO
2NO
NOH
+H
NOH
NO
O2
Mn(II), Co(II)
NO
OH
NOH
O + H +
Minisci, F.; Recupero, F.; Cecchetto, A.; Gambarotti, C.; Punta, C.; Faletti, R.; Paganelli, R.; Padulli, G.Eur. J. Org. Chem. 2004, 109-119.
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Polar Non-radical Mechanism?
NO
+ HOH
B
NHO O
H B
-BH
NOH
+ O
NO
+ HOH
-H
NO O
H
NOH
+ O
Minisci, F.; Recupero, F.; Cecchetto, A.; Gambarotti, C.; Punta, C.; Faletti, R.; Paganelli, R.; Padulli, G.Eur. J. Org. Chem. 2004, 109-119.
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Specific Examples and Illustrations
(1) NO catalyzed oxidations
(2) MGM, MCM and ICM catalyzed isomerization
(3) Silyl enol ether mediated 5-exo and 6-endo cyclizations, and general approach to 4-allyl-oxyl radical cyclizations.
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Polar Radical Pathway of MGM
HOOC
COOHHOOC
COOH
MGM orMethyleneglutarate-mutase
3-methylitaconic acid2-methyleneglutaric acid
XOOC
COOX
XO2C
CO2X
XOOC
COOX
X = H / R /
Newcomb, M; Miranda, N. J. Am. Chem. Soc. 2003, 125, 4080.
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Potential Energy Profile Analysis
Tri-radical intermediate
HOOC
COOH
HO2C
CO2H
HOOC
COOH
12.1 12.1
8.6Energy (kcal/mol)
Reaction Co-ordinate
12.1
Reactant
Newcomb, M; Miranda, N. J. Am. Chem. Soc. 2003, 125, 4080.
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Apparent Paradox in MGM Catalyzed Isomerization
• Rate Constant for cyclization estimated to be 2000 s-1
• Estimation is coupled with partioning of intermediate cyclopropyl carbinyl radical, overall rate constant is estimated to be 10E-3 s-1
,
• Unusual mechanism is possibly involved with polar effects operative
HO2C
CO2H
HO2C
CO2HHO2C
CO2H
Scheme A:
O2C
CO2
O2C
CO2
O2CCO2
Scheme B:
Newcomb, M; Miranda, N. J. Am. Chem. Soc. 2003, 125, 4080.
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Catalytic Mechanism Devoid of 3-exo Cyclization
O2C
H
CO2
H
O2C CO2
H H
CO2
O2CO2C
CO2
HHH
O2C
CO2
HH H
HMethylene-glutarate-Mutase
• Fragmentation results formation of a radical that is stabilized by a through space polar-captodative orbital interactions.
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Solvent Polarity Effect and Limited Acid Catalysis
GS
OCoA G O
S CoA G SCoA
O
G= CO2H (MCM catalyzed rearrangement)G=CH3
(Isobutyryl CoA Mutase catalyzed rearrangement)
PhPh
PhSe
X
OPhPh X
OPhPh
OX
PhPh
X
OX
O
Ph
Ph
X
O
Ph
PhBu3SnH
X=H/Me/SEt
hv
Daublain, P.; Horner, J. H.; Kuznetsov, A.; Newcomb, M. J. Am. Chem. Soc. 2004, 126, 5368.
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Solvent Polarity and Acid Catalysis
CF3CH2OH
AcOH
MeCN
CH2Cl2THF
Cyclohexane
Gasphase
ET(30)
logk
30 40 50 60 70 80
5
7
9
11
TFA(M)
kobs X 10-6
CH2Cl2
Hexane
A: Observed rate constant for reaction of 1st intermediateB: Rate constant of reactions of 1st intermediate in presence ofTFA in CH2Cl2 and in hexane
Daublain, P.; Horner, J. H.; Kuznetsov, A.; Newcomb, M. J. Am. Chem. Soc. 2004, 126, 5368.
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“Partial Protonated” radical
H2N CH C
CH2
OH
O
N
NH
PhPh
O
X
HO
O
CF3
Histidine• Catalytic role of His244 in the catalytic site of MCM catalyzed reaction• Mechanistic reconsiderations - Role of surrounding water in nucleophilicassistance
GNu OX
SCoA
X= or H
G Nu OX
SCoA+ G SCoA
Nu OX
Daublain, P.; Horner, J. H.; Kuznetsov, A.; Newcomb, M. J. Am. Chem. Soc. 2004, 126, 5368.
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Specific Examples and Illustrations
(1) NO catalyzed oxidations
(2) MGM catalyzed isomerization
(3) Silyl enol ether mediated 5-exo and 6-endo cyclizations,and general approach to 4-allyl-oxyl radical cyclizations
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Cyclization of Silyl-enol Ether Radical Cations
OTBDMS OOTBDMS
6-endoO
I
O O
6-endo
+
O
5-exo
hv
hv, AIBN
Bunte, J. O.; Heilmann, E. K.; Hein, B.; Mattay, J.; Eur. J. Org. Chem. 2004, 3535.Curran, D. P.; Chang, C. T.; J. Org. Chem. 1989, 54, 3140.
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Selectivity in 5-exo or 6-endo Radical Cyclization
+
5-exo2.0E-6
6-endo2.6E-6
ProcessRate Constant
• No apparent preference in the formation of a tertiary vs a primary radical
• Can be explained in terms of assuming 5-exo process reversible, besides suitable thermodynamics
Bunte, J. O.; Heilmann, E. K.; Hein, B.; Mattay, J.; Eur. J. Org. Chem. 2004, 3535.
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Steps Involved in photo-cylization ofsilyl-enol ether
O O
hv
-e
SiR3 SiR3 Nu O
OO
Mesolytic
Si–O cleavage
6-endocyclization
H atom abstraction
Bunte, J. O.; Heilmann, E. K.; Hein, B.; Mattay, J.; Eur. J. Org. Chem. 2004, 3535.
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Geometrical Changes Induced by One Electron Oxidation
O Si
-e
O Si
a(C-O-Si):136.1(+8.4)
a(O-Si-C):100.8(-8.2)
d(C-C):1.42(+0.08) A
d(C-O):1.28(-0.08) Ad(Si-O):1.80(+0.11) A
o
o
o
• Weakened Si-O bond leads to a facile SN2- like substitution induced by solvent or other nucleophile
Bunte, J. O.; Heilmann, E. K.; Hein, B.; Mattay, J.; Eur. J. Org. Chem. 2004, 3535.
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Selectivities in Five vs Six-membered Photo-cyclizations of Silyl-enol Ethers
Case I
OTMS O O O
H
H HHH H
H H+ +
Case II 31%41% 28%
OTMSHH
H H
HH
+
O O
90% 10%
Bunte, J. O.; Heilmann, E. K.; Hein, B.; Mattay, J.; Eur. J. Org. Chem. 2004, 3535.
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Calculated Energy Profile for Case I
OTMS O O O
H
H HHH H
H H+ +
O
H OH O
HH O
OHH
0.0
Energy
-1.15
-2.49 -8.39
-9.40
+21-25
+17.9
0.0
+19.72
+21-25
kcal/mol
NOT TO SCALE
Bunte, J. O.; Heilmann, E. K.; Hein, B.; Mattay, J.; Eur. J. Org. Chem. 2004, 3535.
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Potential Energy Profile for Case II
OTMSHH
H H
HH
+
O O
O
OHH OHH
OHOH
2.79 2.79
0.0
-7.46-6.16
Energy
23.5
19
2522
Numbers in kcal/mol
Bunte, J. O.; Heilmann, E. K.; Hein, B.; Mattay, J.; Eur. J. Org. Chem. 2004, 3535.
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How General Are These 5-exo vs 6-endo Selectivities?
• Substituents that increase in HOMO coefficient along C-5 lead to more 6-endo product
• Substituents that can not cause the increase in C-5 HOMO coefficient lead tomore 5-exo product
R1,
H H
H Me
H C(Me)3
H Ph
Me H
Me Me
Me C(Me)3
5-exo/6-endo
98/2
69/31
46/54
7/93
98/2
82/18
37/63
R2
O MeR2R1 OR1
R2 O
HR2
R1
H-YY H-Y Y
6-endo5-exo
Hartung, J.; Kneuer, R.; Rummey, C.; Bringmann, G. J. Am. Chem. Soc. 2004, 126, 12121.
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Reaction Model for Analysis
OR2
O O
O
R2
O
R2
OR2 OR2
OR2 O
R2
R2R2O
R2
O R25-exo-chair
5-exo-boat
6-endo-chair
6-endo-boat
Starting geometry TS cyclized radical
alkoxy radical
Hartung, J.; Kneuer, R.; Rummey, C.; Bringmann, G. J. Am. Chem. Soc. 2004, 126, 12121.
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A True Ion or A Polar Radical ?Cl
PhN
N
hv Cl
Ph
CCl4Ph
Cl Cl+ CCl3
PhPh
Cl Cl
Cl ClPh
ClCl Cl
Cl ClCl
ClCl Cl
Cl Cl
Dimerizations
Ph
ClCl
PhPhCl
Cl Ph
++
+
Ph
ClCl CCl3
δ+ δ−
Ph
ClCl CCl3
Ph
ClCCl4
Ph
ClCl CCl3
Ph
Cl Cl
- Polar atom transfer
- Ylide
- Dissociative electron transfer
Jones, M. B.; Jackson, J. E.; Soundararajan, N.; Platz, M. S. J. Am. Chem. Soc. 1988, 110, 5597.
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Answer
1.1E8PhMeCCl3CN(pOMe)-PhCCl
4.0E8MeCNCCl3CNPhCCl
8.4E8PhMeCCl2(CN)2PhCCl
1.4E7PhMeCCl3CNPhCCl
3.8E4MeCNCCl4PhCCl
k (M-1 s-1)solventCl donorcarbenePh
ClCl CCl3
δ+ δ-
Ph
ClCl CCl3
Ph
ClCCl4
Ph
ClCl CCl3
Ph
Cl Cl
1
2
3
Substituting Cl by CN:
• Expected to retard the rate for ylide mechanism (2)
• Accelerate the rate for polar atom transfer (1 & 3)
Jones, M. B.; Jackson, J. E.; Soundararajan, N.; Platz, M. S. J. Am. Chem. Soc. 1988, 110, 5597.Jones, M. B.; Maloney, V. M.; Platz, M. S. J. Am. Chem. Soc. 1992, 114, 2163.
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Conclusions & Remarks1. Polar effect in radical reactions originates from a polar TS that is often
achieved through, electronic perturbation (from Orbital interactions,medium polarity etc) Geometrical changes and Nonperfect synchronization (NPS)
2. NO catalyzed oxidations, MGM, MCM and ICM catalyzed isomerizations,and radical cyclizations were shown as representative examples where
polar effects were found to be operative
3. Distinguishing a polar radical TS and completely ionic TS can often be challenging
4. Higher level computations can help in understanding polar effects in radical reactions
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Diels-Alder Reaction in Water
• Enhanced hydrophobic interaction in the TS
• Internal Pressure
• Higher polarizability of TS
• Increased Endo selectivity
• Problems of solubility & possible remedy by tryingcosolvents, constrained medium (zeolite, micellarmedium etc).
Bresslow, R.; Rideout, D. J. Am. Chem. Soc. 1980, 102, 7816.Otto, S.; Engberts, J. B. Pure Appl. Chem., 2000, 7, 1365.
EDG
EWG
+
EWGEDG
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Acknowledgement1. Parents - Asim K Nandi & Parbati Nandi
2. Dr. Jackson, Dr. Dye, Dr. Wagner, Dr. Wulff
3. Michael (SiGNa)
4. Labmates - Simona, Misha, Andrea, Jennifer, Tulika, Karrie, and Kaushik
5. Friends - Sampa, Supriyo, Sanjukta, Aparajita,Sam, Parul, Bani, Brad
6. Roommate - Neil
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Typical Dipole-Moments of Radicals
2.52010HOO0.00103N3
0.80287HCC
1.25684ClCHCHCH2
2.87736ClCH2CHCH3
2.38577CH2CHCHOH0.07868CH2CHCH2
0.43937CH3CH2
0.00615CF3
0.00141CH3
Dipole Moments in DebyeSpecies
http://www.colby.edu/chemistry/webmo/mointro.html
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Pyramidalization Effects on Energy and Dipole Moment
QuickTime™ and aTIFF (LZW) decompressor
are needed to see this picture.
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Measure of Solvent Polarity• Energy of charge transfer as a intramolecular (ET ) or intermolecular (Z) process
Z Scale
N
Ph
PhPh
PhPh
O
ET Scale
N
COOCH3
CH2CH3
IN
COOCH3
CH2CH3
Ihv
Reichardt, C. Chem. Rev. 1994, 94, 2319.
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Catalytic Mechanism of MCM CatalyzedIsomerization
CoASO
HH
CO2
CoASO
HCO2
HCO2
CoASO
CO2
H
CoASO
CoASO
HH
CO2H
CoASO
HH
CO2H
H
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MO of NO
σ∗
σ 2s
σ∗1s
σ 1s
π 2p
π∗ 2pπ∗ 2p
π 2p
σ 2p
σ∗ 2p
E 2s
NO
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Captodative Effects
CN OMeOMe
NC
16126
Barrier of C-C rotation in kcal/mol
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Factors Responsible For the Selectivities
• Rate constants for cyclizations
• Life-time of the radical intermediates
• Length of the new bond formed (Beckwith-Houk model)
• Endothermicity or exothermicity
• Steric or geometrical optimization
Bunte, J. O.; Heilmann, E. K.; Hein, B.; Mattay, J.; Eur. J. Org. Chem. 2004, 3535.
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Calculated Charge and Spin Distribution
O Si O Si O
0.010.15+0.18
0.52
0.20
0.690.18
-0.040.03
0.030.03
0.03
+0.29
charge spin spin
0.05
-0.05
TMS:+0.17
+0.17
Bunte, J. O.; Heilmann, E. K.; Hein, B.; Mattay, J.; Eur. J. Org. Chem. 2004, 3535.