noncovalent interactions: electrostatic...

Noncovalent Interactions: Electrostatic Effects

Evans Group Seminar09/25/2009

Egmont Kattnig

Charge-charge

Charge-diplol

Dipole-dipol

Charge-induced dipole

Dipol-induced dipole

Dispersion

Van der Waals repulsion

Hydrogen bond

NH3+ -OOC

NH3+ O

H

H

q- q+

OH

H

q- q+ OH

H

q- q+

NH3+ q- q+

OH

H

q- q+ q- q+

q-

q-q+

q+

N H O

1/r

1/r2

1/r3

1/r4

1/r5

1/r6

1/r12

Energydependenceon distance

Noncovalent Interactions

Electrostatic Energy:Israelachvili, J. Intermolecular and Surface Forces, 2nd ed.; Academic Press, London, 1991.

Electrostatic Effect and Bond Energies:Wiberg, K. B. „The Role of Electrostatic Effects in Organic Chemistry“, J. Chem. Edu. 1996, 73, 1089.Wiberg, K. B. „The Interaction of Carbonyl Groups with Substituents“, Acc. Chem. Res. 1999, 32, 922.Kemnitz, C. R.; Loewen, M. J. „Amide Resonance Correlates with a Breadth of C-N Rotation Barriers“,J. Am. Chem. Soc. 2007, 129, 2521.P. R. Rablan „Is the Acetate Anion Stabilized by Resonance or Electrostatics? A Systematic StructuralComparison“, J. Am. Chem. Soc. 2000, 122, 357.

Electrostatics and Conformation:Wiberg, K. B., Wang, Y.-g., Petersson, G. A., Bailey, W. F „Intramolecular Nonbonded AttractiveInteractions: 1-Substituted Propenes“, J. Chem. Theory Comput. 2009, 5, 1033.Gooseman, N. E. J.; O‘Hagan, D.; Peach, M. J. G.; Slawin, A. M. Z., Tozer, D. J.; Young, R. J. „AnElectrostatic Gauche Effect in b-Fluoro- and b-Hydroxy-N-ethylpyridinium Cations“, Angew. Chem.Int. Ed. 2007, 46, 5904.Smith, M. D.; Woerpel, K. A. „Electrostatic interactions in cations and their importance in biology andchemistry“, Org. Bio. Chem. 2006, 4, 1195.

Oxocarbenium Chemistry:Yang, M. T.; Woerpel, K. A. „The Effect of Electrostatic Interactions on Conformational Equilibria ofMultiply Substituted Tetrahydropyran Oxocarbenium Ions“, J. Org. Chem. 2009, 74, 545.Lucero, C. G.; Woerpel, K. A. „Stereoselective C-Glycosylation Reactons of Pyranoses: TheConformational Preference and Reaction of the Mannosyl Cation“, J. Org. Chem. 2006, 71, 2641.

Dipol Controlled Nucleophilic Addition:Wipf, P.; Jung, J.-K. „Nucleophilic Additions to 4,4-Disubstituted 2,5-Cyclohexadienones: CanDipole Effects Control Facial Selectivity?“, Chem. Rev. 1999, 99, 1469.

Inductive Effect: Polarization of electron density in bonds, caused primarily by electronegativity differences.

Electrostatic Effect: Interaction between atomic charges in various parts of a molecule.. The effect is transmitted through space (i. e. a field effect).

Ion-Dipole Interaction:

for r > l: point-dipol approximation (l→0)

Charge-Charge Interaction: Coulomb Law

repulsion between like charges

attraction between unlike charges

between a unit charge (Q = e) anda dipol (u = ql = 1 D) in vacuum (ε = 1)

no interaction energy

Solid line: energy for l = 0.1 nm and l = 0.2 nm

dashed line: energy for l = 0

maximal Interaction Energy for cationswith a H2O molecule at 300 K

Na+: w(r, θ = 0°) = 22.9 kcal/mol (39kT)

Li+: 29.8 kcal/mol

Mg2+: 59 kcal/mol

Charge-Dipol Interaction Energy

Some Examples:

Bond Dissociation Energy (BDE)

Pauling Electronegativities

C2.55

N3.04

O3.44

F3.98

Si1.90

P2.19

S2.58

Cl3.16

difference in electronegativity leads to bond polarisation (charge separation)

coulombic attraction increases bond strength

bond polarisation affects σ and π bonds

H3C X CH3 + X

BDE (kcal/mol)

H3C CH3

H3C NH2

H3C OH

H3C F

89

86

92

110

H3C SiH3

H3C PH2

H3C SH

H3C Cl

90

70

74

83+C F-

-C Si+

+C Cl-

Increasing Electronegativity

π bond strength

C O

C C 64 kcal/mol

84 kcal/mol

K. B. Wiberg et al. J. Chem. Edu. 1996, 73, 1089.

Stabilization in Polyfluorinated Compounds

CF4 + 3 CH4 4 CH3F !H = +53 kcal/mol

C

F

F

C

F+

F-

C

F

Fn(F) !"(CF)

C

F

H

C

F

F

!+

!- !-

!-

2!+

Valence-Bond Theorie MO Theorie

Electrostatic Effect

CH3F

CH2F2

CHF3

CF4

-0.743

-0.744

-0.744

-0.737

-0.429

-0.429

-0.421

-0.405

-0.550

-0.576

-0.576

-0.551

AIM NPA GAPT

Atomic Charges at Fluorine

why is CF4 more stable than CH3F?

F is a poor lone pair donor

Increased positive charge at carbon leadsto stronger electrostatic attraction

C

SiH3

SiH3

!+

2!-

!+

C

F

SiH3

!-

!+

!+

C(SiH3)4 + 3 CH4 4 CH3(SiH3) !H = +13 kcal/mol

FCH2SiH3 + CH4 !H = -7 kcal/molCH3F CH3SiH3+

H3CCNH2

O

H3CCNH2

+

O-

H3CC+

NH2

O-

Amide Resonance and CO-X Interactions

H3C

O

NH2

+ H3C CH3H3C

O

CH3

+ H3C NH2

Group Transfer Reaction

H3C

O

N H3C

O

NH

H

HH

Rotation

Group Separation Energy (GSE)Interaction Energy between CO and C-N

ΔHπ

rotational barrier: ~ 15 kcal/mol

π Electron Interactions

K. B. Wiberg et al. Acc. Chem. Res. 1999, 32, 922.

H3C

O

X

+ H3C CH3H3C

O

CH3

+ H3C X

F

OH

NH2

Cl

+16.7

+22.7

+19.3

+6.8

0.0

+11.5

+13.9

0.0

+16.7

+11.2

+5.4

+6.8

GSE !H" !H#

H

S

X

+ H3C CH3H

S

CH3

+ H3C X

F

OH

NH2

Cl

+4.7

+15.7

+18.4

+0.1

0.0

+12.3

+18.0

0.0

+4.7

+3.5

+0.5

+0.1

GSE !H" !H#

H3CC+

X

O-

Electrostatic Interactions more importantfor electronegativ X (F, OH)

H3CC

X+

O-

C=S bond less polarizedπ bond contributions more important

Me-X BDE (kcal/mol)

°•

planar structure

90° rotated structure (without ΔHπ)

Slope of ~1.5: increased positive charge at carbon leads to stronger CO-bond

negative charge at carbon destabilizes the compound e.g. CO-Si, CO-CF3,…

Ac-X BDE (kcal/mol)

!+H3C

C+

SiH3

O-

!-!-

H3CC+

F

O-

!+H3CC+

CH3

O-

Comparison Ac-X and Me-X Bond Disoziation Energy

H3C CH3

O

H3C NH2

O

H3C OH

O

H3C F

O

1.222 ! 1.220 ! 1.212 ! 1.185 A

CO-bond length

Acidity of Carboxylic Acids

H3CCO-

O

H3CCO

O-

H3CC+

O-

O-

Increasing Polarisation of Ac-X

H3CCOH

O

H3CCO-

O

+ H+

H3C OH + H+H3C O-Methanol: pKa(H2O) = 15.5

Acetic acid: pKa(H2O) = 4.76

stabilisation by resonance electrostatic stabilisation

P. R. Rablan J. Am. Chem. Soc. 2000, 122, 357.

H3C

X

H3C X

E favored by 1.1 kcal/mol Z favored X = OMe

X = Cl

0.53 kcal/mol

0.68 kcal/mol

X = Br 0.45 kcal/mol

Nonbonded Interactions in 1-substituted Propenes

H3C

CH3

H3C CH3

Relative Energies (E→Z) in kcal/mol

HF calculations do not include electroncorrelations (no attractive van der Waals terms)

DFT allows some correction for electron correlationCCSD(T) gives superior correction for this effect.

Energie difference in HF and MP2 calculations for X = Cl, Br, SMe: attractive van der Waals interaction?

calculated Energies independend from used method for X = F, OMe

K. B. Wiberg et al. J. Chem. Theory Comput. 2009, 5, 1033.

H3C CH3

H H

!+ !-H3C F

H H

H3C Br

H H

Steric Repulsion Electrostatic Attraction (X = F, OMe)

Dispersion(X= Cl, Br, OMe)

calculated C=C-CH3 angeles

cis-bond angels larger than trans

difference in bond angles increaseswith size (F→Cl)

contributions to relative energies (kcal/mol)

cis preference is combination ofCoulombic attraction and

dispersion interactions

F

H H

HH

F

H

H F

HH

F

gauche favoured by 0.5-1.0 kcal/mol

Electrostatic Gauche Effect

stereoelectronic effect: σ(CH) → σ*(CF)

1,2-Difluoroethan:

β-Fluoroethylamin

NH2

H H

HH

F

H

H NH2

HH

F

0.9 kcal/mol

H

H NH

HH

FH

-1.0 kcal/mol0.0 kcal/mol

NH3+

H H

HH

F

H

H NH3+

HH

F

-5.8 kcal/mol0.0 kcal/mol

β-Fluoroethylammonium

OH

H H

HH

F

H

H OH

HH

F

H

H O

HH

FH

OH2+

H H

HH

F

H

H OH2+

HH

F

H

H OH+

HH

FH

0.0 kcal/mol -0.3 kcal/mol -2.0 kcal/mol 0.0 kcal/mol -4.4 kcal/mol -7.2 kcal/mol

2-Fluoroethanol protonated 2-Fluoroethanol

gauche preferred in charged system: electrostatic Attraction

D. O‘Hagan et al. Angw. Chem. Int. Ed. 2007, 46, 5904.

N

H H

HH

F

H

H N

HH

F

N+

H H

HH

OH

H

H N+

HH

OH

R = H: 0.0 kcal/mol -3.7 kcal/mol

-3.1 kcal/mol

0.0 kcal/mol -0.05 kcal/mol

0.0 kcal/mol -3.7 kcal/mol

N+

H H

HH

F

R

H

H N+

HH

F

R

R = NMe2: 0.0 kcal/mol

N-(2-fluoroethyl)pyridinium cation

no preference in uncharged system

N-(2-hydroxyethyl)pyridinium cation

C2‘ endo C3‘ endo

NAD+

NH2+

HOHO

OH

OHNH2

+

OH

OH

favored by 4.0 kcal/mol


pKa = 7.5

pKa = 9.5

exo favored by 3.4 kcal/mol

endo favored by 4.1 kcal/mol

N+

Me

Me

F

N+

Me

Me F

Me

Me F

Me

Me

F

NN

CN

F

H

H

O

O

N+N

CN

H

H

O

O

H

F

H+


O

MeO

!+!-

!-

O

MeO

Electrostatic Effects and Conformational Analysis

electrostatic stabilization through space

shorter distance between axial-OMeand carbonyl carbon

K. A. Woerpel et al. Org. Biomol. Chem. 2006, 4, 1195.

O OAc

X

SiMe3

SnBr4

O C3H5

X

O C3H5

X

4

OBn

Me

01:99

94:06

cis/trans

decrease in selectivity from F to I: no anchimeric assistence

O+

4

Nu

Me

O+

4

Nu

OBn!-

Electrostatic Effects in Oxocarbenium Chemistry

O

X+

Nu

F

Cl

05:95

14:86

Br

I

31:69

28:72

pseudoaxial configuration favoured by electrostatic interactions


O+

4

Nu

OBn!-

O+

3

Nu!-BnO

O+

4

Nu

!-

H

BnO 2

O+

Nu

!-OBn

H2

O

BnO

4

O

3

OBn

O

OBn

2

99:01 β-selectivity

O

BnO

OPO(OR)2

4

OBn

OBn

OBn

SiMe3

TMSOTf

O

BnO

OBn

OBn

OBn

!

89:11 β-selectivity 83:17 β-selectivity

α-isomer only

electrostaticstabilisation

no electrostatic preferencehyperconjugation from C2-H-bond

K. A. Woerpel et al. J. Org. Chem. 2009, 74, 545.

Oxocarbenium Chemistry

O

BnO

OPO(OR)2

4

OBn

OBn

OBn

SiMe3

TMSOTf

O

BnO

OBn

OBn

OBn

!

disfavored because ofsyn-pentan interaction

stereoelectronicallydisfavored

stereoelectronically disfavored

α-isomer only

Curtin Hammett scenario possible

O+

4

Nu

OBn

BnO

BnO

OBn

Nu

O+

4OBn

BnO

OBn

OBn

Nu

D-Mannosyl Cation

O

BnO

AcO

TMSCN

EtAlCl2 O

BnO

NC

4

SiMe3

SnBr4

OOAc

Me

O

Me

3

O+BnO

H

O+

H

BnO

!-

Nu

Nu

3

3

OBn

O+

O+

H OBn

H

H

Nu

4

4

Electrostatic stabilisation of oxocarbenium ions

dr = 99:01

dr = 94:06

SiMe3

SnBr4

OOAc

BnO

O

BnO

3

inside attack provides staggered product

favored by 2.5 kcal/moldr = 96:04


OR

O

COOMe

Pb(OAc)3

MeO

pyridineOR

O

COOMeAr

R = Me

R = TBS

80:20

95:05

dr

!+

O-MeOOC

O SiR3

4

Electrostatic stabilisation of an anionic intermediate

electrostatic interaction between enolate andelectropositive silicon stabilizes transition state

J. P. Konopelski et al. Org. Lett. 2002, 4, 4121.

Nucleophilic Additions to 4,4-disubstituted 2,5-Cyclohexadienones

OR'

OR MeMgBr

ORR'

OHMe

Diastereoselectivity?

OO

OMe

OTMS

!

"

OMe

OMe

"'42%

8.6:1 (32%) 17.7:1 (93%) 4.8:1 (81%)

O

O

O

Me

OBz

OMe

OH

5.5:1 (53%) 8.2:1 (85%)7.9:1 (26%)

!'58%!' 39%

OO O

32:1 (79%)

O

O

O

11:1 (27%)

P. Wipf et al. Chem. Rev. 1999, 99, 1469.

O

O

8.6:1

O

OO

32:1!

O

Me

OMe

4.8:1

diastereoselectivity correlates with dipol moment

dipol-controlled nucleophilic addition

OCF3CF2

OMe

1:5 (72%)

!

β-selectivity by inverted dipol

noncovalent interactions: electrostatic...

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