¹H‐NMR Spectra of Cyclohexa‐1,4‐dienes and Cyclohexenes Annellated to Bicyclo[2.2.1]hept‐2‐enes. The Inter‐Ring Homoallylic H,H Coupling Constants as Stereochemical Probes

Abstract

l]hept-2-enebond n-anisotropy. Vicinal as well as intra-ring homoallylic coupling constants are consistent with a small puckering of the cyclohexa-I ,4-diene rings toward the rndo -face. The allylic exo-methylene protons are more deshielded than the cvzdo-protons independent of the nature of the suhstituents, the nature of the bridges, and the degree of unsaturation of the annellated systems. These results constitute a probe for the configuration of cyclohexa-l,4-dienes and cyclohexenes annellated to these bicyclic skeletons.Introduction. -In the course of our studies on the synthesis of anthracyclines [I-41 based on the Diels-Alder additions of exocyclic s-cis-butadiene moieties grafted onto 7-oxabicyclo[2.2. Ilheptane derivatives 1, we observed 'H-NMR spectra of the corresponding adducts 2 with measurable homoallylic 'J(H,H) coupling constants of ca. 1 Hz between the bridgehead protons of the 7-oxabicyclo[2.2. llheptene systems and the allylic protons of the annellated cyclohexene moieties [3-51. This was true for the exo-protons only; no such long-range coupling could be detected for the endo-allylic protons. In order to determine whether this feature could be taken as a probe for the configuration of the Diels-Alder adducts 2, we prepared a series of cyclohexenes and cyclohexa-1,Cdienes annellated to various bicyclo[2.2.l]hept-2-ene and 7-oxabicyclo[2.2.l]hept-2-ene skeletons. We report now on their high-field (360 MHz) 'H-NMR properties and show that the inter-ring homoallylic 'J(H,H) coupling constants indeed constitute the probe we were looking for.

Anomeric Effect on Geminal and Vicinal JHH NMR Coupling Constants

“…The first distinction to be made is between hyperconjugative interactions (a) within the coupling pathway and (b) involving nearby bonds or antibonding orbitals. Those of type a seem to enhance 3 J HH couplings,15b as well as the J FC term of 3 J CH couplings . Those of type b in an H−C−C−H fragment and corresponding to either hyperconjugative interactions into the (σ* C - H ) antibonding orbitals or hyperconjugative interactions from the C−H bond orbitals cause a decrease in the 3 J HH coupling .…”

“…Such a trend suggests that the influence of negative hyperconjugative interactions on 3 J HH SSCCs is more important for a 0° conformation than for a 150° conformation. The influence of hyperconjugative interactions on 3 J HH couplings are known to be more complicated than that on the 2 J HH couplings . The first distinction to be made is between hyperconjugative interactions (a) within the coupling pathway and (b) involving nearby bonds or antibonding orbitals.…”

“…The influence of the anomeric effect on 2 J HH coupling constants was, by far, less studied than the influence of such interactions on 1 J CH couplings . It is known that experimental 2 J HH couplings cover a very wide range of values from about −24 to +43 Hz, and it is accepted that they depend on a variety of factors. , Recently, for a CH 2 moiety placed α to an sp 2 carbon atom, for example, a carbonyl moiety such as acetaldehyde ( 1 ) or a CC double bond such as that in propene ( 2 ) (Scheme ), eq 1 was written for different values of φ, the rotation angle around the C(sp 2 )−C(sp 3 ) bond, to account for the DFT-calculated FC contribution to the 2 J HH coupling constant where ΣΔocc is the sum of the differences between the NBO occupancies of the σ C α - H 2,3 bonding orbitals containing both coupled protons for an angle φ and those corresponding to φ = 0° (and the analogous quantity for the respective (σ* C α - H 2,3 ) antibonding orbitals). For 1 , we obtained J 0 = −19.38, A = 324, and B = 1249, whereas for 2 , the following eq 1 parameters were reported: J 0 = −18.30, A = 616, and B = 720.…”

“…Vicinal proton−proton coupling constants, 3 J HH , in H−C−C−H fragments are a powerful tool for structural elucidation and conformational analysis of molecules in solution because of their Karplus-type dependence on the corresponding dihedral angle. During the last two decades, several factors that affect the standard Karplus curve, such as bond angles, bond lengths, substituent electronegativity, and orientation, were studied. , It is already known that hyperconjugative interactions involving either bonding or antibonding orbitals belonging to the coupling pathway could have a significant influence on the respective FC term of such vicinal couplings, although it seems that the relationship between hyperconjugative interactions and vicinal couplings is more complicated than the effect of such interactions on geminal couplings. Apparently, the FC term of other types of couplings involving 13 C and 15 N nuclei are similarly influenced by hyperconjugative interactions …”

“…15,21 It is already known that hyperconjugative interactions involving either bonding or antibonding orbitals belonging to the coupling pathway could have a significant influence on the respective FC term of such vicinal couplings, 18 although it seems that the relationship between hyperconjugative interactions and vicinal couplings is more complicated than the effect of such interactions on geminal couplings. Apparently, the FC term of other types of couplings involving 13 C and 15 N nuclei are similarly influenced by hyperconjugative interactions. 13 To gain further insight into the effect of hyperconjugative interactions on 2 J HH and 3 J HH coupling constants, we report the study of 2-methylthiirane (5) and 2-methyloxirane (6) (Scheme 1), which were chosen as model compounds.…”