Bispidine Platform as a Tool for Studying Amide Configuration Stability

Bispidine Platform as a Tool for Studying Amide Configuration Stability Full article

Journal

Molecules
, E-ISSN: 1420-3049

Output data

Year: 2022, Volume: 27, Number: 2, Pages: 430 Pages count : 1 DOI: 10.3390/molecules27020430

Tags

3,7-diazabicyclo[3.3.1]nonanes; dynamic stereochemistry; barriers of amide rotation; NMR spectroscopy; X-ray diffraction study; quantum chemical calculations

Authors

Krut’ko Dmitry P. ¹ , Medved’ko Alexey V. ² , Lyssenko Konstantin A. ¹ , Churakov Andrei V. ³ , Dalinger Alexander I. ¹ , Kalinin Mikhail A. ^1,2 , Gudovannyy Alexey O. ^1,4 , Ponomarev Konstantin Y. ⁵ , Suslov Eugeny V. ⁵ , Vatsadze Sergey Z. ¹

Affiliations

1	Lomonosov Moscow State University
2	Федеральное государственное бюджетное учреждение науки Институт органической химии им. Н.Д. Зелинского Российской академии наук
3	NS Kurnakova Institute of General and Inorganic Chemistry RAS
4	D. Mendeleyev University of Chemical Technology of Russia
5	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of Siberian Branch of Russian Academy of Sciences

In this work, the solution conformations of seventeen 3,7-diacyl bispidines were studied by means of NMR spectroscopy including VT NMR experiments. The acyl groups included alkyl, alkenyl, aryl, hetaryl, and ferrocene moieties. The presence of syn/anti-isomers and their ratios were estimated, and some reasons explaining experimental facts were formulated. In particular, all aliphatic and heterocyclic units in the acylic R(CO) fragments led to an increased content of the syn-form in DMSO-d6 solutions. In contrast, only the anti-form was detected in DMSO-d6 and CDCl3 in the case when R = Ph, ferrocenyl, (R)-myrtenyl. In the case of a chiral compound derived from the natural terpene myrtene, a new dynamic process was found in addition to the expected inversion around the amide N-C(O) bond. Here, rotation around the CO-C=C bond in the acylic R fragment was detected, and its energy was estimated. For this compound, ΔG for amide N-C(O) inversion was found to be equal to 15.0 ± 0.2 kcal/mol, and for the rotation around the N(CO)–C2′ bond, it was equal to 15.6 ± 0.3 kcal/mol. NMR analysis of the chiral bispidine-based bis-amide was conducted for the first time. Two X-ray structures are reported. For the first time, the unique syn-form was found in the crystal of an acyclic bispidine-based bis-amide. Quantum chemical calculations revealed the unexpected mechanism for amide bond inversion. It was found that the reaction does not proceed as direct N-C(O) bond inversion in the double-chair (CC) conformation but rather requires the conformational transformation into the chair–boat (CB) form first. The amide bond inversion in the latter requires less energy than in the CC form.

Krut’ko D.P. , Medved’ko A.V. , Lyssenko K.A. , Churakov A.V. , Dalinger A.I. , Kalinin M.A. , Gudovannyy A.O. , Ponomarev K.Y. , Suslov E.V. , Vatsadze S.Z.
Bispidine Platform as a Tool for Studying Amide Configuration Stability
Molecules. 2022. V.27. N2. P.430. DOI: 10.3390/molecules27020430 WOS Scopus РИНЦ OpenAlex

Submitted:	Dec 4, 2021
Accepted:	Jan 5, 2022
Published print:	Jan 10, 2022
Published online:	Jan 10, 2022

Web of science:	WOS:000758821600001
Scopus:	2-s2.0-85123437180
Elibrary:	48145477
OpenAlex:	W4205110459

DB	Citing
OpenAlex	10
Web of science	9
Scopus	8
Elibrary	9