Conformational Analysis of Nine-Membered Cyclic Acetals. Stereoelectronic Effect in 2,4- and 3,5-Benzodioxonine Derivatives

Abstract

Conformations of the title compounds were examined using DFT calculations and NBO analysis in order to find the origins of their conformational preferences. The most stable conformations were TBC and TCBtype-1 for the 2,4- and 3,5-benzodioxonine derivatives, respectively. In both of these conformations the acetal moiety adopts the g+/-g+/- geometry. The NBO analysis yielded values of the stabilization energy associated with the stereoelectronic nO --> sigmaC-O* interactions that were highest for conformations other than the global minima. Conformers displaying the strongest interactions followed different patterns of atom arrangement within the acetal moiety, namely g+g-, and those in which one or both of the torsion angles within the C-O-C-O-C segment were close to 90 degrees . Steric repulsion caused by alkyl substituents at the anomeric carbon was found to influence the strength of the nO --> sigmaC-O* stabilization through modification of bond lengths and torsion angles. The adopted ground-state conformations result from accommodation of steric repulsions and stabilizing stereoelectronic interactions. It was shown that DFT calculations of conformational preferences of acetals together with GIAO prediction of 13C chemical shifts should be a useful methodology for studies on conformation and conformational equilibria of acetals in solution.

Conformational analysis of cis‐3, 5‐dioxa‐bicyclo[5.4.0]undecane and its 4‐substituted derivatives by DNMR, molecular modeling, and GIAO/DFT methods

“…Coalescence is also observed in the 13 C NMR spectra for all compounds. Signals of all pairs of exchanging carbon atoms are split, in the lowest temperature spectrum, into two equal populated signals, whereas the signal of C-3 and carbon atoms of the substituents at C-3 do not change, thus indicating that only one conformation is present in solution.…”

“…With the exception of 3, where a dynamic process broadens both signals, in the remaining compounds they display an AM part of AMX spin system. 13 C NMR spectra of 1, 2, and 4 taken at room temperature contain five sharp signals corresponding to the methylene and methine groups of the bicyclic skeleton. In the case of the 3,3- dimethyl substituted derivative 3 even at temperature of 286 K, the dynamic process is slowed down causing broadening of signals of C-1/C-5, C-6/C-9, and C-7/C-8.…”

“…To study the nature of the dynamic processes, a series of variable temperature 1 H and 13 C NMR experiments in the range of 303-150 K were carried out. The expanded part of the CH 2 O region of 4b in 1 H spectrum is shown as an example in Fig.…”

“…In this paper, we are presenting the conformational behavior of cis-3,5-dioxa-bicyclo [5.4.0]undecane (1) and some of its alkylsubstituted derivatives (2-4) using a combination of the 1 H and 13 C DNMR spectroscopy and molecular modeling methods carried out at the DFT level of theory. Moreover, experimental 13 C NMR chemical shifts of the studied compounds are compared with those obtained via GIAO-DFT calculation of shielding constants.…”

“…Moreover, experimental 13 C NMR chemical shifts of the studied compounds are compared with those obtained via GIAO-DFT calculation of shielding constants.…”