Stereoelectronic Effects Recent Advances and New Insights

Transcription

1 Stereoelectronic Effects Recent Advances and ew Insights An Evans Group Afternoon Seminar Keith Fandrick ctober 10, 2003 I. II. III. IV. Introduction to yperconjugation and B Analysis The Role of yperconjugation in Cyclohexane σ-acceptor Abilities and Trends Recent Examples Keywords: hyperconjugation, stereoelectronic, cyclohexane, conformational energies, σ-acceptor, equilibrium, Ceiplak, Anh, ring-opening, silyl, Fock, B, methylcyclohexane, dioxane, W-effect, Perlin,

2 Ethane and Methanol, Staggered vs Eclipsed Conformations Arguments for yperconjugation Ethane Methanol Staggered Eclipsed Staggered Eclipsed Deleted yperconjugative Interaction o Deletion o yperconjugation o Vicinal yperconjugation o Geminal yperconjugation Preferred Conformer Staggered Eclipsed Eclipsed Staggered Deleted yperconjugative Interaction o Deletion o yperconjugation o Vicinal yperconjugation o Geminal yperconjugation Preferred Conformer Staggered Eclipsed Eclipsed Staggered Goodman, L.; J. Phys. Chem. A, 2002, 1642 Goodman, L.; ature, 2001, 565

3 The Stereoelectronic Interactions of Ethane yperconjugation not Sterics leads to the Staggered Conformation Energy Lowering Due to yperconjugation rbital drawings E σ C-X σ C- E stabilization σ C σ C Resonance Theory Representation Evans D. A.; Chem. 206 notes, 2001 Alabugin, I. V.; J. Am. Chem. Soc., 2001, 3175 Goodman, L.; ature, 2001, 401, 565

4 B Analysis -Structures optimized at the F/6-31G**, MP2/6-31G**, and B3LYP/6-31+G* levels using GAUSSIA 94/98 packages -B 4.0 program was interfaced with the GAUSSIA 94/98 packages -B program transforms the canonical delocalized artee-fock (F) M's into localized hybrid orbitals (natural bonding orbitals, B) -Filled B's describe the hypothetical "strictly" localized Lewis structures -Deviation of the molecule from the optimized structure form the B description can be used to measure the energetics of delocalizations/hyperconjugation -Energetics of the delocalizations were estimated from the second order perturbation approach and calculated by deletion of the corresponding off-diagonal elements of the Fock matrix in the B basis Alabugin, I. V. J. rg. Chem. 2000, 65, 3910 Weinhold F. Encyclopedia of Computational Chemistry; Schleyer P. 1998, p 1792

5 + B Analysis of Cyclohexane The Four Main yperconjugation Interactions (5.1) kcal/mol σ C σ* C - ax eq 3.2 (4.0) kcal/mol σ C * σ CC Energies correspond to RF/6-31G** (B3LYP/6-31+G**) 2.2 (3.3) kcal/mol σ CC * σ C Alabugin, I. V.; J. rg. Chem. 2000, 65, 3910

6 B Analysis of Cyclohexane eq ax Bond Length, Å Bond RF/6-31G** B3LYP/6-13+G** Σ E del, Kcal/mol 1 J C, z RF B3LYP C- ax C- eq Calculated longer bond lengths correspond to lower C- coupling constants, in accord with a ormal Perlin effect (J Cax < J Ceq ) -Analysis indicates: C- bonds are better donors than C-C bonds Alabugin, I. V.; J. rg. Chem. 2000, 65, 3910 Perlin, A. S.;Tetrahedron Lett. 1969, 292

7 1-Methyl-1-cyclohexyl Cation Two Distinct Chair Conformations, yperconjugative effects Longer C-C bonds Longer C- bonds Relative Energy 0.6 kcal/mol 0 kcal/mol 0.25 kcal/mol -At least two different structures are observed for the methyl-cyclohexyl cation by MR Rauk, A.; J. Am. Chem. Soc., 1996, 3761

8 1,3-Dioxane, W-Effect? Summary of Delocalizing Interactions for C- bonds In 1,3-Dioxane -Almost equal J Cax and J Ceq at C5 -Reverse Perlin effect with alkyl and aryl substituted 1,3-dioxanes -n eq σ* C <1 kcal/mol (W-effect) Alabugin, I. V.; J. rg. Chem.2000, 65, 3910

9 B analysis of 1,3-Dioxane, extra interaction Proposed W-effect Proposed ew interaction n eq σ* C lp σ C p * -W-effect found to be small, <1 kcal/mol. -P orbital for a lone pair is a better donor than the corresponding sp 3 lone pair. -ew interaction is favored due to better orbital overlap. σ Ceq σ * C -Interaction is smaller than, but it serves to tip the balance of delocalizing interactions in the favor of "equatorial" delocalization. Alabugin, I. V.; J. rg. Chem. 2000, 65, 3910 Cuevas, G.; J. Am. Chem. Soc., 2002, 124, 13088

10 Conclusions from B anlysis Summary of equatorial interactions for dioxane and dithiane S S 1.8 -B anlaysis, E(del), correlates well with C- bond lengths in cyclohexane, 1,3-dithiane, and 1,3-dioxane -B analysis of 1,3-dioxane and 1,3-dithiane suggests the donor ability of σ-bonds are: C- > C-S > C-C >-C ~ C- > S-C Square denotes the C(2)- eq in 1,3-dioxane Alabugin, I. V.; J. rg. Chem.2000, 65, 3910

11 σ-acceptor Abilities: Trends For Monosubstituted Ethanes, C 3 C 2 X + X X - Correlation of E del for σ C- σ C-X interactions and Electronegativity -E del calculated by deletion of the off-diagonal Fock matrix elements between interacting orbitals, B analysis σ-acceptor abilities correlate with electro -negativity across a period E del kcal/mol -Down a row, σ-acceptor abilities increase Electronegativity Alabugin I. V.; J. Am. Chem. Soc., 2002, 124, 3175

12 σ-acceptor Abilities: Trends The rigin of the σ-acceptor Trends in Ethane Correlation of E del for σ C- σ C-X Interactions and Electronegativity Correlation energy of σ C-X and Electronegativity E del kcal/mol σ C-X Energy, a.u. Electronegativity Electronegativity E σ C-X -E del depends on the energy separation of the M and LUM σ C- E stabilization

13 σ-acceptor Abilities: Trends E del kcal/mol Correlation of E del and E(2) Second-order perturbation analysis of the Fock Matrix in the B basis set Ε (σ/f/σ E(2) = - η ) 2 σ ε σ - ε σ = - η σ F ij 2 Ε is the energy difference between the σ and σ orbitals η σ is the population of the donor σ orbital E(2) kcal/mol F ij is correlated with the orbital overlap matrix element S ij and the acceptor orbital polarization -E(2) overestimates stabilizing interactions, but shows excellent correlation with E del -Energetics of delocalizations depends on: E, orbital overlap, and polarization of the acceptor orbital Alabugin I. V.; J. Am. Chem. Soc.,2002, 124, 3175 etenyl, A.; J. rg. Chem.,2003, 68, 5705

14 σ-acceptor Abilities: Trends Delocalizing interactions with substituted ethenes: X - X + -alogen acceptor abilities are F < Cl > Br -In ethanes, the E term is more important, In ethenes, the significance of F ij increases -Rationale for the increase dependence of F i j is the shorter C=C bond relative to C-C -F ij depends on the overlap of the donor and acceptor orbitals, thus it has an exponential dependence on the distance between the two orbitals -Anh's warning: one must compare similiar systems when using FM Alabugin I. V.; J. Am. Chem. Soc., 2002, 124, 3175 Anh,. T.; ew J. Chem., 1997, 21, 861

15 Testing the Steric Model, Methylcyclohexane Elongation of the C α C β bond by 0.3Å a γ a Me β α a a γ β α Me 0.3 Å 0.3 Å E = kcal/mol E = kcal/mol Parameters and Energetics (kcal/mol), Bond Lengths ( Å) and Angles (deg.) Conformation State E Cα-Cβ Cβ-Cγ Cβ-Cα-C Me a -Cγ-Cβ a - C Me -Cγ Axial Axial Ground Distorted Equatorial Equatorial Ground Distorted Consistent with Steric Model Riberiro, D. S.; J. rg. Chem.,2003, 68, 6780

16 Testing the Steric Model, Methylcyclohexane Compression of the C α C β and C β -C γ bonds by 0.2 Å a a γ a Me a α β γ β α Me 0.2 Å 0.2 Å E = kcal/mol E = kcal/mol Parameters and Energetics (kcal/mol), Bond Lengths ( Å) and Angles (deg.) Conformation State E Cα-Cβ Cβ-Cγ Cβ-Cα-C Me a -Cγ-Cβ a - C Me -Cγ Axial Axial Ground Distorted Equatorial Equatorial Ground Distorted ot Consistent with Steric Model -ote: same argument used to explain higher conformational energies of 2-methyl-1,3-dioxanes Riberiro, D. S.; J. rg. Chem.,2003, 68, 6780

17 Testing the Steric Model, Methylcyclohexane Bending the C α C β -C ME bond angel inward by 4 o a γ a Me β α E = 1.18 kcal/mol 4 o 4 o a γ a β α Me E = 1.21 kcal/mol Parameters and Energetics (kcal/mol), Bond Lengths ( Å) and Angles (deg.) Conformation State E Cα-Cβ Cβ-Cγ Cβ-Cα-C Me a -Cγ-Cβ a - C Me -Cγ Axial Axial Ground Distorted Equatorial Equatorial Ground Distorted ot Consistent with Steric Model -ote: bending the angel outward is consistent with steric model Riberiro, D. S.; J. rg. Chem., 2003, 68, 6780

18 Testing the Steric Model:2-Methyl-1,3-dioxane a γ a 2 o a 2 o Me β α γ a β α Me a γ a 2 o α β Me a γ a 2 o Me α β E = 0.37 kcal/mol E = 0.33 kcal/mol E = 0.35 kcal/mol Parameters and Energetics (kcal/mol), Bond Lengths ( Å) and Angles (deg.) E = 0.37 kcal/mol Conformation State E Cα-β β-cγ β-cα-c Me a -Cγ-β a - C Me -Cγ Axial Axial Axial Ground Distorted Distorted Equatorial Equatorial Equatorial Ground Distorted Distorted Expect greater steric interactions due to shorter C- bonds -Compression of C α -C β bond by 0.2 Å leads to a smaller energy gap than expected -Bending β -C α -C Me bond inward and outward does not show energetics consistent with steric model

19 Methylcyclohexane, AIM Atomic Energies The Role of Ring Strain Stuctural optimizations were performed with Gaussian 94 AIMPAC was used to calculate AIM atomic energies AIMPAC/AIM allows one to calculate the the energetics of a part or a group of given structure More Stable by A-value =1.8 to 2.2 kcal/mol Energies (kcal/mol) are the comparison of the equatorial versus axial energy differences of the indicated group or atom Energies in Blue correspond to stabilization (lower energy) relative to the equatorial conformer, energies in Red indicate destabilization (higher energy) relative to the equatorial conformer Cuevas G.; J. Phys. Chem. A, 2003, ASAP

20 t-butylcyclohexane, AIM Atomic Energies The Role of Ring Strain 5.23 More stable A-Value = 5.36 kcal/mol Energies (kcal/mol) are the comparison of the equatorial versus axial energy differences of the indicated group or atom Energies in Blue correspond to stabilization (lower energy) relative to the equatorial conformer, energies in Red indicate destabilization (higher energy) relative to the equatorial conformer Cuevas G.; J. Phys. Chem. A, 2003, ASAP

21 Alternate Explanation For Equatorial Preference σ C σ CC X X Me σ* CC σ C X X Me σ* C σ * σ σ C * C C -Following Alabugin's results, ΣE(del) ax > ΣE(del) eq, Authors propose that the equatorial preference is a reflection, or partly due, to the axial preference for the methine hydrogen due to greater hyperconjugative interactions -The proposition offers an alternative explanation for the trend of conformational energies of halocylocohexanes, E CX ; Br<Cl<F. The trend is due, or partly due to the order of acceptor abilities of the anti-bonding C-X orbitals. -The explanation also provides a rationale for the low conformational energy of methylthianium. It does not have an acceptor orbital to stablize the equatorial conformation. + S Me Methylthianium Riberiro, D. S.; J. rg. Chem., 2003, 68, 6780 Alabugin, I. V.; J. rg. Chem.2000, 65, 3910

22 Alternate Explanation For Equatorial Preference Testing Ribeiro's ypothesis Is there a relationship between the acceptor abilities of substituents on substituted cyclohexane and conformational energies? X σ C σ * CX X σ C σ * C If there is, than one should see a correlation between A values and the acceptor abilities of C-X bonds Result: o correlation, but not so fast... ote, acceptor orbital energies are taken from Alabugin ethane calculations yperconjugative Stabilizing Energy (kcal/mol) Plot of A-values vs yperconjugative Stabilizing Energy F A-value; G o (kcal/mol) A-values: D. A. Evans, Chem. 206 notes, 2001, lecture 6. Acceptor Energies: Alabugin, I. V.; J. Am. Chem. Soc., 2002, 3175 I Br R2 = Cl

23 Alternate Explanation For Equatorial Preference Testing Ribeiro's ypothesis Same analysis, but using the acceptor orbital values from the ethene calculations X σ C σ * CX X σ C σ * C ote: and Me change their acceptor orbital abilities depending on their conformations yperconjugative Stabilizing Energy (kcal/mol) F Plot of A-values vs yperconjugative Stabilizing Energy Ts Br Ac Cl Me y = x R 2 = A-value; G o (kcal/mol) Me 9.33 Me 8.40 A-values: D. A. Evans, Chem. 206 notes, 2001, lecture 6. March. S.; Advanced rganic Chemistry, 2001 Acceptor Energies: Alabugin, I. V.; J. Am. Chem. Soc., 2002, 3175

24 Epimerization Equilibrium of 2-Aryl-1,3-,-eterocycles Epimerization 1 X X X Epimerization 2 Me Me X Me Me X Me Me X X = p- 2, p-cf 3, p-br, p-cl,, p-f, p-me, p-me, p-me 2 etenyi, A.; J. rg. Chem., 2003, 68, 5705

25 Epimerization Equilibrium of 2-Aryl-1,3-,-eterocycles Epimerization 1 Plot of G o vs ammett-brown σ + values Epimerization 1 Epimerization 2 X G o, kcal/mol Me Me X Epimerization 2 ammett-brown σ + values p-me 2 p- 2

26 Epimerization Equilibrium of 2-Aryl-1,3-,-eterocycles Second-order perturbation analysis of the Fock matrix, B basis Stabilization ennergy from a single donoracceptor interaction (σ/f/σ E(2) i j = -η ) 2 σ ε σ - ε σ = -η σ F i j 2 Ε Plot of Theoretical Stereoelectronic Stabilization Energies vs G o for Epimerization 1 Difference in yperconjugative Stabilization Energies in the Epimerization Equilibrium Σ E ij = ΣE ij R - Σ E ij L R and L denotes right and left sides of the epimerization equilibrium Σ E i j (kcal/mol) -A similiar plot for Epimerization 2 displays an R 2 value of G o (kcal/mol)

27 Epimerization Equilibrium of 2-Aryl-1,3-,-eterocycles The relevant hyperconjugative stabilizing interactions for Epimerization 1 Lewis Structures of the relvant interactions n -σ * C3-Aryl n Aryl -σ * C3- n Aryl -σ * C3-4 Aryl -Aryl Aryl - Aryl

28 Epimerization Equilibrium of 2-Aryl-1,3-,-eterocycles Role of donor-acceptor energy difference and Fock matrix element Plot of Donor-Acceptor rbital Energy Difference vs ammett-brown coefficient Plot of the Fock Matrix Element vs The ammett- Brown coefficient Ε 1 (x10 3 mol/kcal) F i j 2 (Kcal/mol) σ + σ + E(2) i j = -η σ F i j 2 Ε -Delocalizing interaction energies are more dependent upon the Fock matrix element, due to the higher changes in the Fock matrix energetics relative to the donor acceptor energy difference terms.

29 Epimerization Equilibrium of 2-Aryl-1,3-,-eterocycles Role of bond polarization in hyperconjugative stabilization Graphical Representation of the Polarization Coefficients on C3 p-me 2 Ar Ar Ar p- 2 Ar Ar Ar σ C-Ar σ C- σ C- -F ij is correlated with the overlap matrix element S i j and acceptor orbital polarization -Conformational changes of the heterocyles are around 1 o -Bond polarization change of σ C3-Aryl and the decrease ot the other two interactions accounts for the stabilization energies and the observed epimerization equilibrium

30 The Cieplak Model: Recent Advances Recent Literature Example: Reduction of Snoutanones and Adamantanones ab 4 -Me + Cieplak's Model - - R R = C CC 3 CC CC 2 C 2 C 3 R 84 : : : : : 44 R - - R ab 4 -Me R R = C CC 3 CC CC 2 C 2 C 3 + R 59 : : : : : 47 R FM prohibits such an interaction. The interactions should weaken and enlongate the forming bond in the transition state Mehta, G.; J. Chem. Soc., Perkin Trans. 1, 1998, 1895 Kaneno, D,; Tomoda, S.; rg. Lett., 2003, R

31 The Cieplak Model: Alternate Explanation Carbenes: Experimental Results 250 o C + R R R R A B R Ratio A : B 2 Si(C 3 ) 3 90 : : : 74 ote: the exact mechanism of carbene insertion is not known, but above results appear to contradict Ceiplak's Model Knoll, W.; rg. Lett., 2003, 2943

32 The Cieplak Model: Alternate Explanation Carbenes: Experimental Results R' R' R hv, R'- R A R + B R R Solvent Ratio A : B 2 Si(C 3 ) 3 Me Me Me 15 : : : 31 R' = Me or c-c Si(C 3 ) 3 c-c 6 12 c-c 6 12 c-c : : : 31 Similiar results with polar and nonpolar solvents discount electrostatic control of substrate's orientation Knoll, W.; rg. Lett., 2003, 2943

33 The Cieplak Model: Alternative Explanation Carbenes: Tomoda's Calculations Tomoda's Calculated Transition States: Me Insertion Cyclohexane Insertion Å Å Å Å -umbers show the difference in bond length from the indicated bonds and the corresponding bonds on the opposite side of the molecule -Longer bond lengths correspond to greater anti-periplanar anomeric effect -Support Cieplak's Model?? Tomoda, D.; rg. Lett., 2003,

34 The Cieplak Model: Alternate Explanation Carbenes: Tomoda's Calculations AP Bond Lengths and Bond Populations anti AP bonds syn R TMS A anti syn anti syn Bond Elongation ( ) Å R TS GS TS %BE GS TS BP Methanol Bond Population (e) Bond lengths decrease and bond populations increase from going from GS to TS TMS A anti syn anti syn Cyclohexane The analysis shows that the AP effect actually decreases in the TS, and the AP effect destabilizes the TS -These results are inconsistant with Cieplak's and Anh's models Cieplak, A. S.; J. Am. Chem. Soc., 1981, 4550 Ahn,. T.; Top. Curr. Chem., 1980, 145

35 The bending Model The Cieplak Model: Alternative Explanation Carbenes: Bending of the Carbene carbon R Distal Conformer R Proximal Conformer The substitutent Role a) induction b) hyperconjugation R

36 The Cieplak Model: Alternative Explanation Carbenes: Bending of the Carbene Bridge Plot of Difference in Energy of the Proximal and Distal conformers vs Ln of the observed insertion ratios R R Distal Conformer Proximal Conformer E = E pro - E dis ln(syn/anti) Cyclohexane Calculations performed on Gaussian 98 Me r 2 = 0.99 E (kcal/mol)

37 Recent Stereoelectronic Effects Silyl Effects on Ring-pening Reactions of Cyclobutenes 140 o C, 1 h n-c 8 17 m-xylene n-c % yield SiMe 2 Ph PhMe 2 Si 140 o C, 1 h SiMe 2 Ph n-c 8 17 m-xylene n-c 8 17 n-c >96 % yield CMe o C, 1 h CMe 3 PhMe 2 C m-xylene n-c % yield SiMe 2 Ph PhMe 2 Si 140 o C, 1 h SiMe 2 Ph PhMe 2 C m-xylene PhMe 2 C PhMe 2 C >95 % yield Murakami, M.; Angew. Chem. Int. Ed., 2001, 189

38 Recent Stereoelectronic Effects Silyl Effects on Ring-pening Reactions of Cyclobutenes C'-C-Si angle = 132 o Si σ C C' 1.67 C Si σ C' C'-C-Si angle = 92 o C'-C-Si- dihedral angle = 170 o E (kcal/mol) Si 3 Si Si 3 Murakami, M.; Angew. Chem. Int. Ed., 2001, 189

39 Cautions with using FM Anh's Warnings -FM gives good predictions in ~80 % of the cases studied by Anh -FM should only be applied when the following conditions are met: nly apply FM to the transition states (in most cases) Apply FM only to systems in which the FM are well separated from other M Apply FM to systems that can be described by a single electronic configuration nly compare systems that are similiar and undergoing the same reaction (Ethane and ethene acceptor orbital abilities are different) -Almost all violations of FM theory occur when these restrictions are not met Anh,. T.; ew J. Chem., 1997, 861

40 Conclusions -The hyperconjugative interactions due to σ-bonds are relevant. These interactions have shown importance in bond lengths, MR coupling constants, appear to be involved in conformational energies, and transition state energies -All three terms of the Fock matrix equation need to be considered to account for the hyperconjugation interactions. F i j (orbital orientation and proximity and polarizations) and E (M and LUM energy levels separation) -B analysis (E(del) or E(2) methods) provides an estimate of the hyperconjugative interactions allowing one to quantitatively unravel their relative importance. -yperconjugative interactions due to σ-bonds are relatively weak. These interactions should be considered but other interactions can be more important