Discovery of a Long-Range Perlin Effect in a Conformationally Constrained Oxocane

Abstract

Herein, we present the crystal structure, NMR J analysis, and conformational and natural bond order analyses of tricyclic oxocane (1), resulting in the discovery of a long-range Perlin effect at C4 and C5. The normal Perlin effect (NPE) of Δ(1)JC-H = 18.38 Hz at C5 is the largest to date for a nonanomeric methylene due to an unprecedented through-space n → σ* stabilizing interaction. The NPE at C4 where Δ(1)JC-H = 6.91 Hz is nearly double those found in cyclohexanone.

Revisiting the Long-Range Perlin Effect in a Conformationally Constrained Oxocane

“…In order to check whether the experimental or theoretical results were correctly reported, the target compound 1 was synthesized using the same procedure described by Berry . The experimental values of 1 J C–H were measured using two different NMR pulse sequences: the perfect 1 J CH -resolved HSQC, developed to measure this type of J -coupling minimizing the overlap problems observed in the coupled-HSQC which was used in the original paper, and the sel -HSQC available in any Bruker NMR equipment.…”

“…Compound 1 was synthesized using the procedure described by Berry. The structure was confirmed using the DP4+ method and comparison with literature data H 5 and H 8 ), 1.99 (m 14 , H 3‑eq and H 5‑eq ), 1.77 (m 14 , H 3‑ax and H 5‑ax ), 1.18 (s, H 11 and H 12 ), 1.14 (dtt, J = 13.5, 6.9, 2.3 Hz, H 4‑eq ).…”

“…Recently, Berry and co-workers discovered an even larger difference between SSCCs (18.38 Hz) when studying a constrained tricyclic oxocane derivative (1) (Figure 1). 5 These values caught our attention and they were not reproduced by NMR spectra performed in our laboratory, possibly due to the poor resolution in which the experimental NMR spectra was acquired by Berry and co-workers. In this study, we present a revision of the 1 J C−H values applying experimental and theoretical analysis regarding the molecule 1, and theoretical analysis was also performed for analogous compounds named tricyclic thiocane (2), tricyclic azacane with the hydrogen from N−H group oriented in a pseudoequatorial position (3), tricyclic azacane with the hydrogen from N−H group oriented in a pseudoaxial position (4), tricyclic azacane with the phenyl group bounded to the nitrogen atom oriented in a pseudoequatorial position (5), tricyclic octane (6) and cyclohexanone (7) to investigate the effect of oxygen from furan five-membered ring on 1 J CH .…”

“…From experimental data listed on Table , is unquestionable that there is a difference on 1 J CH between axial and equatorial orientation of C–H bond, but not in the extension as previously reported . The Δ J is actually close to a regular Perlin effect as occurs in the anomeric carbon of 1,3-dioxane (around 9 Hz) …”

“…Taking into account the theoretical and experimental data (Table ), it is clear that the experimental values of 1 J C–H obtained using either pulse sequence are in great agreement with the calculated ones. When entries 4 and 5 were compared it can be seen that the difference between the 1 J C4–H pair is 7.8 Hz instead of 18.34 Hz as was previously reported, and between entries 2 and 3 ( 1 J C3–H pair) the difference is 2.2 Hz instead of 6.91 Hz as reported …”