Conformational insights into furo‐ and thieno[2,3‐b]indolines derived from coupling constants and molecular modeling

Abstract

The extent to which conformational preferences of fused heterocyclic five-membered rings change with the nature of the heteroatom (O and S) was investigated in furo- (1, 2) and thieno[2,3-b]indolines (3, 4) by the combined use of 1H NMR spectroscopy and density functional theory (DFT) calculations. In contrast to the behavior observed for pyrroloindolines, the furo- and thienoindolines exist in solution in only one conformer, with structures in the 2E-2T3 (1,2) and 2T3-E (3,4) North/West region of the pseudorotational wheel, and with pseudorotation phase angles (P) of 315.8, 311.6, 337.2 and 331.6 degrees, respectively.

Synthesis and Biological Evaluation of (−)- and (+)-Debromoflustramine B and Its Analogues as Selective Butyrylcholinesterase Inhibitors

“…The spectral and analytical data were consistent with those reported. 31 (1-Benzyl-5-methoxy-1H-indol-3-yl)acetonitrile (23d). Prepared by stirring 23b for 24 h according to general procedure 1.…”

“…Starting indole 23a is commercially available. Indoles 23b and 23e , oxindoles 24a , 24e , 25a , 25h , and 25k , as well as pyrrolidinoindolines 4a − c , , 5a , 5h , 5k , 10 , and 22 , are known and were synthesized using procedures described from this laboratory.…”

“…13 C NMR (CDCl 3 ) δ 151.9, 136.1, 136.0, 134.1, 127.7, 122.8, 119.9, 119.4, 119.2, 108.9, 63.4, 60.2, 46.9, 46.8, 42.9, 38.2, 26.0, 25.7, 18.0, 17.9. EIMS m/z (relative intensity) 299 (M+, 19), 230 (100), 162 (68), 144 (91), 69 (31). HRMS (ESI/APCIMS) calcd for C 20 H 29 NO + H, 300.2327; found, 300.2327.…”

Computational studies of 13C NMR chemical shifts of saccharides

“…26,29,30 The popularity of ab initio and DFT studies of NMR parameters for saccharides is increasing rapidly. 15,[31][32][33][34][35][36][37][38][39] These studies include calculations of NMR chemical shifts, 15,[32][33][34][35]37,39 spin-spin coupling constants, 33,38 electron paramagnetic resonance parameters, and g-tensors of free radicals in sugar systems. 36 Other computational studies of central importance in this context are those by Klein, 40 Barrows et al, 26 Csonka et al, 41 and Corchado et al 42 Klein 40 studied 1 C 4 and 4 C 1 conformers of b-D-glucopyranose at the DFT level.…”

Chemistry of the Hexahydropyrrolo[2,3-b]indoles: Configuration, Conformation, Reactivity, and Applications in Synthesis

“…Furthermore, the hexahydrofuro[2,3- b ]benzofuran skeleton, common to the aflatoxins, shows a significant preference for C2 substituents to adopt the endo-configuration under equilibrating conditions as demonstrated by the experimental work of Civitello and Rapoport, Harris and co-workers, and Townsend and co-workers with systems 22 , 23 , and 24 , respectively, and by computational work by Messeguer and co-workers and Morales-Rios et al The Morales-Rios group also has carried out spectroscopic and computational studies on the hexahydrofuro[2,3- b ]indole 25 and the hexahydrothieno[2,3- b ]indole 26 skeletons and find that, in common with the pyrrolo[2,3- b ]indole and furo[2,3- b ]benzofurans, the predominant conformation has C2-puckered in toward the endo-surface . Overall, the preference for C2 substituents for the endo-configuration and for the C2 carbon to adopt an endo-conformation in this entire series of bicyclo[3.3.0]octane-based heterocycles appears to be primarily driven by the relief of torsional strain.…”