Transition state force fields

Transcription

1 Transition state force fields Transition states from force fields Q2MM development Scope of TSFF Q2MM example Properties of force field TS s

2 Transition states from force fields Norrby, Jensen, Theor. Chem. Acc. 2003, 109, 1 TSFF, Q2MM E = E 1 E 2 ± ( E 1 E 2 ) 2 J 2 reactant FF EVB, FF, MCMM SEAM product FF J = 0 ( ) E = min E 1,E 2 or ( ) E = max E 1,E 2

3 Transition state force fields (TSFF) Derive a new force field where the TS structure is treated as a minimum. Eksterowicz, ouk, Chem. ev. 1993, 93, TSFF reactant: not treated product: not treated No activation barriers! nly relative energies of transition states (selectivity)

4 Creating a TSFF Force field parameterization: tune parameters to reproduce data ML n Bond lengths Angles Charges Sensitivity to distortion! lder work: guess structures, data estimation Current: TS structural data & charges from high-level QM

5 Distortion in transition states In a real TS, distortion along the reaction coordinate lowers the energy The reaction coordinate must be modified in TSFF (energy minimum) eal TS PES: PES in TSFF: Distortions in other directions should be reproduced faithfully

6 Q2MM Norrby, J. Mol. Struct. (Theochem) 2000, 506, 9 Parameterization from QM data, structures, charges, relative energies. Vibrational data (essians) is modified before being used as reference data: λ λ Diagonalization: = X T WX Eigenvalue replacement: λ 1 λ x, W W Forming the new essian: = X T W X λ X λ

7 Q2MM uses Cannot calculate activation barriers ²G Cannot calculate chemoselectivity Nu nly useful for comparing conformations and diastereomers of transition states Stereoselectivity

8 Q2MM example; the asymmetric WE reaction () 2 P * C* C* Ph TMS Enantiodivergent C* TMS C* C* TMS Enantioselective desymmetrization eview: ein, eiser, Acta Chem. Scand. 1996, 50, 369.

9 Q2MM model development E 1 E 2 () 2 P * * * () 2 P * - * * Ph * verlays, QM & MM TS

10 Q2MM results Product ratios: E/Z, E(:S), Z(:S) Calc ²G* C* C* 2 0 * Me ipr E:Z 39:61 95:5 E(:S) 95:5 84:16 Z(:S) 9:91 28: () 2 P Ph TMS C* C* TMS -6 Exp. ²G* =Me Me ipr E:Z 28:72 94:6 E(:S) 5:95 6:94 Z(:S) 91:9 46:54 C* E:Z >99:1 E(:S) 5:95 (90% ee) Norrby, Brandt, ein, J. rg. Chem. 1999, 64, 5845.

11 The WE reaction; source of selectivity FAE-type selectivity ne side blocked, only Si-face reacts P() 2 X Nu * P() 2 X * X X Nu X Fixed * P() 2 X Enantiodivergent * X Determined by X

12 TSFF missing terms Shortening eality: a shortening of the forming bond leads to changes in the conjugated bonds Force fields: bonds are independent Elongation Stretch-Stretch term: E = k ss (l-l 0 )(l -l 0 ) Error in the essian, 2 E/ x y

13 esponse to steric crowding True TS TS force field Q2MM Intrinsic PES Steric demand = = = esulting PES

14 esponse of intersecting surfaces Similar gradient Different gradient different geometry TSFF SEAM EVB Geometries systematically offset Enantioselectivity?