ESI for Organic and Biomolecular Chemistry
This journal is (c) The Royal Society of Chemistry 2006

Studies in sigmatropic rearrangements of N-prenylindole derivatives - a formal enantioselective synthesis of tryprostatin

A. Sofia P. Cardoso, M. Manuel B. Marques, Natarajan Srinivasan, Sundaresan Prabhakar, Ana M. Lobo and Henry S. Rzepa

Supporting Information

Details of Calculations

The Gaussian 03 program was employed: ( Gaussian 03, Revision C.01, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr., T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez, and J. A. Pople, Gaussian, Inc., Wallingford CT, 2004). Solvation corrections were applied at the SCRF(CPCM) level (V. Barone and M. Cossi, J. Phys. Chem. A, 1998, 102, 1995. Transition states were characterised via the form of the single negative root of the computed Hessian matrix.

Analysis of Calculations

Prior coordination of a BF3 to the N changes the character of the subsequent sigmatropic pericyclic shifts from entirely covalent to having a significant degree of ionic character involving a partially bound allylic cation. Coordination of this ionic component is preferred endo to the aromatic ring at the transition state geometry; the exo isomer is 4.1 kcal/mol higher in energy. The barrier (corrected for solvation) corresponds to a reasonably facile thermal reaction. The form of the calculated transition state normal mode is shown animated below, and effectively corresponds to that of a [1,2] migration.

Endo [1,5] Sigmatropic Transition State for N- to C-2 Migration Exo [1,5] Sigmatropic Transition State for N- to C-2 Migration
-922.99408 [-922.75306]a {-922.99638}b νi 88 cm-1 -922.98447 [-922.74656]a {-922.98490}b νi 248 cm-1
ΔG298 25.8 {19.6}b ΔG298 29.9 {26.6}b
a Total energy in Hartree at the B3LYP/6-31G(d) level, [Corrected for thermal energy and entropy]. b {SCRF, CPCM solvation model, dichloromethane} >