Boat and chair transition states of 1,5-hexadiene

Abstract

CQ dication stabilizes the DNA structure by electrostatic interaction between the positive charges on CQ and the phosphate groups on DNA. In this complex the side chain of CQ is visualized as forming a bridge across the minor groove of the double helix. Since the distance across the minor groove, -10.5 A, is larger than the maximumo possible extended distance between N-2 and N-3, 7.5 A, and much larger than the distance observed in the crystal, 5.5 A, a N-2,N-3 complex across the minor groove would appear to be a quite unfavorable possibility. Moreover, the pmr protonation data33 point to a dication in which positive charges are located at N-1 and N-3 rather than N-2 and N-3. The N-1-N-3 distance in this case is appreciably larger in the crystal, 14.1 A, and in solution, 6.7 (20") and 8.1 8, (48"), than N-2-N-3, and a bridging complex would appear to be more favorable. However, the present solution data, though determined for the free base form of CQ, do suggest that the side chain has considerable conformational flexibility and is influenced by a variety of factors including solvent medium, temperature, and pH.Acknowledgments. The authors wish to acknowledge Dr. Fred E. Hahn for helpful discussions on the properties of antimalarial drugs. We also wish t o thank Dr. J. M. Stewart for kindly providing the crystal coordinate data.former was determined for the diprotonated form of CQ (N-1 and N-3 protonated) while the latter relates to the free base. Electrostatic repulsion between the positive charges would tend to force the CQ molecule into a more open structure with an extended side chain. Interaction with phosphate groups further acts to stabilize the extended form in the cation. On the other hand the unusual buckling of the side chain in solution may arise in part from an intramolecular dipole-induced dipole type of interaction between the N-3 ethyl groups and the r-electron system of the quinoline ring. Such an interaction has its counterpart in the wellknown intermolecular dipole-induced dipole interactions between polar aliphatic amides, amines, etc., and various aromatic ring systems. The key factors favoring this type of interaction, namely a polar acceptor and a well-defined r-electron donorr ing, are both present in CQ.3. Chloroquine Interaction with DNA. Several attempts have been made to relate the conformational features of CQ to its binding interaction with doublestranded DNA. Hahn and O'Brien34 have recently made the interesting suggestion, based on studies of the effect of CQ on the thermal stability of DNA, that the (34) R. L. O'Brien and F. E. Hahn, Antimicrob. Ag. Chemother., 315 (1966). Communications to the Editor Boat and Chair Transition States of 1,5-Hexadiene1 Sir:The stereospecific Cope rearrangement of acyclic 1,5dienes continues to attract theoretical i n t e r e~t~-~ of increasingly more quantitative ambitions. 4,5 Supplementing the previous stereochemical and kinetic6 investigation, we here report discovery of a second degenerate rearrangement of 1,5-hexadiene-one that requires an add...

Density Functional Study of the Oxy-Cope Rearrangement

“…DFT Computations of the B3LYP/6-31G* type by Houk and co-workers [23] confirmed this result. The energies for the chair-and boat-form transition states were in excellent agreement with the experimental results [24] [25]. Jiao and Schleyer [26] also attained good agreement with the experimental data by means of one-determinant method which included electron correlation (e.g., MP4SDTQ/31G*).…”

A computational study of the origin of stereoinduction in NHC-catalyzed annulation reactions of α,β-unsaturated acyl azoliums

“…It is widely accepted that chair transition states are generally preferred over the boat transition states in [3,3]-sigmatropic rearrangements. 14 Boat transition states are less common, but Ireland-Claisen transformations have been identified that preferentially proceed via boat TSs. 15 Our calculations of the protonated boat and chair transition states derived from the R - and S -hemiacetals 9 gave a strong preference for the chair transition states [by > 5 kcal/mol over the corresponding boat TSs].…”

Are boat transition states likely to occur in Cope rearrangements? A DFT study of the biogenesis of germacranes

“…The chair TS ( TS6-3 ) is still more stable, the energy difference between TS5-3 and TS6-3 is almost the same than in TS1b-2 and TS4-2 , but the energy of boat TS ( TS5-3 ) decreases to 38.0 kcal/mol, which is small enough to be overcome at 200 °C. Thus, hemiacetalization lowers the activation energy of the boat Cope TS which allows the reaction to be completed at a temperature significantly lower than the temperature that a standard boat TS would need (≈260 °C) [10]. …”

“…It is known that 1,5-dienes suffer Cope rearrangements at temperatures between 200 and 300 °C, but some structural changes in the diene, such as the anionic oxy-Cope transformation allows the reactions to happen at temperatures below 0 °C [9]. The Cope rearrangement is a [3,3]-sigmatropic reaction and in general, occurs through a single transition state (TS), which has, normally, a chair conformation due to the higher energy of the boat conformation [2,7,10–19]. In this mechanism, the electron density of the TS is delocalized into the six carbon atoms [20–22].…”