First examples of bispidine-ferrocene cyclophanes

Медведько, А. В.; Krut’ko, D. P.; Gaisen, S.V.; Churakov, Andrei V.; Minyaev, Mikhail E.; Moiseeva, Anna A.; Lemenovsky, D.A.; Yu, Haojie; Вацадзе, С. З.

doi:10.1016/j.jorganchem.2021.121945

Cited by 5 publications

(13 citation statements)

References 39 publications

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“…Compounds 1a [42], 1b-d, 1b -1d , [25] 1l, 2, [19] 1f, 1h-1k [27] were prepared as described earlier.…”

Section: Methodsmentioning

confidence: 99%

“…At the same time, the anti-form would be more stable in less polar solvents and, presumably, in the crystal form since the crystallization of molecules with a smaller dipole moment is more preferable. A CSD search returns 19 structures of bispidine-based bisamides (tricyclic compounds of the cytisine type are excluded) [16][17][18][19][20][21][22][23][24][25], out of which only 3 possess a syn-conformation in the crystal, and all belong to macrocyclic molecules containing two bispidine fragments [13,20,23].…”

Section: Anti-syn-mentioning

confidence: 99%

“…N,N -Diacyl bispidines have found various different applications in: medicinal chemistry [26] (a review), [27,28]; crystal engineering [29]; macroheterocycle synthesis [13,[18][19][20]23,[29][30][31]; secondary structure nucleators in peptides [22,32]; conformational switching [12,13]; lipid bilayer modifiers [15,33].…”

Section: Anti-syn-mentioning

confidence: 99%

“…Bis-amides 1 and 2 were synthesized previously either from 5,7-dimethyl-1,3-diazaadamantan-6-one by methylene bridge cleavage in the biphasic system benzene-water (compounds 1a [12,35] (for this compound, the acetic acid anhydride was used), 1b, 1c, 1b', 1c' [25], and 1f [27], Scheme 3) or from 1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonan-9one by direct acylation with the corresponding acid chlorides (compounds 1h-1k [27], 1l, and 2 [19], Scheme 4). Amides 1d, 1d', and 1e were prepared by nucleophilic substitution reactions with sodium iodide and sodium azide in acetone, from the corresponding dichlorides (1b and 1b'); the same approach was used for dopamine derivative 3 (Scheme 5; for experimental details, see Section 3 and Supplementary Materials, SM).…”

Section: Synthesis Of Compoundsmentioning

confidence: 99%

“…Typical values for the rotational barriers around amide bonds range from 19.05 kcal/mol (R1 = R2 = R3 = Me, in water [4]) to 14.3 kcal/mol (R1 = R2 = Me, R3 = ferrocenyl (Fc), in CD2Cl2 [5]), being strongly dependent on all three R's (Scheme 1) as well as on the nature of the solvent [6][7][8][9]. Szostak et al established a useful correlation between the barrier of the amide bond rotation and the reactivity of amides in cross-coupling reactions [10].…”

Section: Introductionmentioning

confidence: 99%

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Bispidine Platform as a Tool for Studying Amide Configuration Stability

et al. 2022

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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.

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“…Compounds 1a [42], 1b-d, 1b -1d , [25] 1l, 2, [19] 1f, 1h-1k [27] were prepared as described earlier.…”

Section: Methodsmentioning

confidence: 99%

Section: Anti-syn-mentioning

confidence: 99%

Section: Anti-syn-mentioning

confidence: 99%

Section: Synthesis Of Compoundsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bispidine Platform as a Tool for Studying Amide Configuration Stability

et al. 2022

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Synthesis and Aminomethylation of 2-Amino-4-(2-chlorophenyl)-6-(dicyanomethyl)-1,4-dihydropyridine-3,5-dicarbonitrile N-Methylmorpholinium Salt

et al. 2022

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Sequential reaction of 2-chlorobenzaldehyde, cyanothioacetamide, and malononitrile dimer in the presence of an excess of N-methylmorpholine resulted in the formation of N-methylmorphlinium salt of 2-amino-4-(2-chlorophenyl)-6-(dicyanomethyl)-1,4-dihydropyridine-3,5-dicarbonitrile. The resulting salt reacts under Mannich conditions with primary amines and an excess of formaldehyde to form substituted 2-alkylamino-4-(dicyanomethylene)-3,7-diazabicyclo[3.3.1]non-2-ene-1,5-dicarbonitriles. Structure of the key compound was confirmed by single crystal X-ray diffraction analysis.

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