Using Minisci reaction for Modification of the tris-dioximate metal clathrochelates: free-radical substitution at the glyoximate fragment of an iron(ii)-encapsulating cage framework Текст научной статьи по специальности «Химические науки»

Clathrochelates Клатрохелаты

Макрогэтэроцмклы

http://macroheterocycles.isuct.ru

Paper Статья

DOI: 10.6060/mhc161182b

Using Minisci Reaction for Modification of the tris-Dioximate Metal Clathrochelates: Free-Radical Substitution at the Glyoximate Fragment of an Iron(II)-Encapsulating Cage Framework

Alexey B. Burdukov,a@ Mikhail A. Vershinin,3 Natalie V. Pervukhina,3 Natalie V. Kuratieva,3 Ilia V. Eltsov,b Alexander S. Belov,c Yan Z. Voloshin,c and Andrei A. Nefedovbd

aNikolaev Institute of Inorganic Chemistry SB RAS, 630090 Novosibirsk, Russia Novosibirsk State University, 630090 Novosibirsk, Russia

cA.N. Nesmeyanov Institute of Organoelement Compounds RAS, 119991 Moscow, Russia dN.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, 630090 Novosibirsk, Russia @Corresponding author E-mail: lscc@niic.nsc.ru

An iron(II) clathrochelate having methylglyoxime rib fragment was treated with Fe(II)/t-BuOOH in 1,4-dioxane. The reaction resulted in substitution of the aldoxime hydrogen with 1,4-dioxanyl fragment by virtue of Minisci reaction mechanism. The resultant cage complex was identified with single crystal XRD, mass-spectrometry, H, 13C, 19F, 11B NMR spectroscopy, and examined with UV-Vis and IR spectroscopy. This reaction extends the range of synthetic approaches applicable for the functionalization of tris-dioximate cage complexes.

Keywords: Clathrochelate, iron(II), 1,4-dioxane, Minisci reaction, X-ray crystallography, multinuclear NMR.

Применение реакции Миниши для модификации трис-диоксиматных клатрохелатов металлов: свободно-радикальное замещение в глиоксиматном фрагменте клетки, инкапсулирующей железо(П)

А. Б. Бурдуков,a@ М. А. Вершинину Н. В. Первухина,a Н. В. Куратьева,а И. В. Ельцов,b А. С. Белов,c Я. З. Волошин,с А. А. Нефедов1^

aИнститут неорганической химии им. А.В. Николаева СО РАН, 630090 Новосибирск, Россия bНовосибирский государственный университет, 630090 Новосибирск, Россия Институт элементоорганических соединений им. А. Н. Несмеянова, 119991 Москва, Россия

Новосибирский институт органической химии СО РАН им. Н.Н. Ворожцова СО РАН, 630090 Новосибирск, Россия @E-mail: lscc@niic.nsc.ru

Клатрохелат железа(11), имеющий метилглиоксиматныйреберный фрагмент, был обработан Fe(II)/t-BuOOH в 1,4-диоксане. В результате реакции альдоксимный атом водорода был замещен на фрагмент 1,4-диоксана по механизму реакции Миниши. Образовавшийся клеточный комплекс был идентифицирован методами РСА, масс-спектрометрии, ЯМР на ядрах H, 13C, 19F, 11B и изучен методами электронной и ИК-спектроскопии. Эта реакция расширяет диапазон синтетических подходов, доступных для функционализации трис-диоксиматных клеточных комплексов.

Ключевые слова: Клатрохелат, железо(П), 1,4-диоксан, реакция Миниши, РСА, ЯМР на различных ядрах.

Using Minisci Reaction for Modification of the Tris-Dioximate Metal Clathrochelates

Introduction

For the first time, free-radical alkylation of electron-deficient aromatic compounds, which is also known as Minisci reaction, was reported in early 1970's.[1] Initially based on an oxidative decarboxylation by persulfate dianion in presence of silver(I) cations as the radical source, further it has been extended to a variety of metal ions[2] and to other radical sources[3-5] as well. Different hydroperoxide - Fe2+ systems are also reported to be suitable to perform this radical reaction.[6,7] Keeping in mind a pseudoaromatic character of the highly conjugated polyazomethine cage frameworks of the tris-dioximate metal clathrochelates and their electron-deficient nature stemming from the positive charge of the encapsulated metal ion, we aimed to apply the Minisci reaction for homolytic alkylation of these macrobicyclic substrates. Homolytic ribbed functionalization of the iron(II) cage tris-dioximates has been earlier performed using free radical substitution of the reactive chlorine atom of a dichlo-roclathrochelate precursor with carbon-centered radicals as shown in Scheme 1(i)[8-13] and by free-radical reductive double alkylation of the methyl substituted azomethine group of the corresponding cage framework as well[14,15] (Scheme 1,ii). Here we report the homolytic radical alkylation of a mono-methylglyoximate iron(II) cage complex FeBd2Mm(BF)2 as a substrate under Minisci reaction conditions, as well as the detailed X-ray structural and spectral characterization of the macrobicyclic product of this reaction.

Experimental

1,4-Dioxane was purified from hydroperoxide by refluxing over KOH pellets and then dried by distillation over P2O5 and CaH2.[16] Commercial 5M decane solution of terf-butyl hydroperoxide (Sigma-Aldrich ®) and other reagents, sorbents and solvents of the reagent grade were used without their additional purification.

1H, 13C, 11B and 19F NMR spectra were recorded using a Bruker Avance III 500 spectrometer (working frequencies 500.03 (1H), 125.73 (13C), 160.33 (11B) and 470.49 MHz (19F)) from CD2Cl2 solution of the clathrochelate under study. 1H and 13C NMR chemical shifts are reported in ppm of the 5 scale and were referred to the signals of this solvent (5H=5.34 ppm for residual protons in 1H NMR spectrum and 5C=53.80 ppm in 13C{1H} NMR spectrum). 11B and 19F NMR chemical shifts were referred to the external standards BF3O(C2H5)2 (5B=0 ppm) and C6H5CF3 (5f=-63.72 ppm), respectively. Heteronuclear C-H correlations (HMBC and HSQC) were applied for the assignment of NMR signals. 1H-1H J-couplings and the positions of the signals of

1,4-dioxan-2-yl substituent were obtained and refined with spinsystem modeling NAMMRIT algorithm; the method of total-lineshape fitting were used. All calculations were carried out using the Bruker Topspin v. 2.1 program package.

Low resolution mass-spectra and exact masses of the compound were obtained using Thermo Scientific Double Focusing System (DFS) high resolution mass-spectrometer. Samples were introduced into mass-spectrometer by direct inlet. The mass spectrometer used electron ionization with 70 eV ionization energy.

X-Ray crystallography. Single crystals of the complex FeBd2(CH3(Gm(diox))(BF)2CH2Cl2, suitable for the X-ray diffraction experiment, were grown from its solution in heptane - dichlo-romethane mixture. The single crystal X-ray diffraction study of this complex was carried out with a Bruker Nonius X8 Apex dif-fractometer equipped with a 4K CCD detector using graphite mono-chromated Mo-Ka radiation (1=0.71073 A) at 150 K. Reflection intensities were integrated using SAINT software[17] and corrected for absorption by a semi-empirical method (SADABS program[18]). The structure was solved by the direct method with SIR2014.[19] All non-hydrogen atoms of the clathrochelate molecule were refined in anisotropic approximation against F2 with SHELX97 software. [20] Hydrogen atoms of the dioxan-2-yl substituent were localized from Fourier synthesis and used to identify its carbon atoms. Further, all hydrogen atoms were set in their geometrical positions and included in the refinement using the riding model. The solvate dichloromethane molecule was disordered; and, thus, was refined isotropically without its hydrogen atoms.

Preparation of FeBd2Mm(BF) : 1,8-bis(2-fluorobora)-2,7,9, 14,15,20-hexaoxa-3,6,10,13,16,19-hexaaza-4,5,11,12-tetraphenyl-17-methyl-bicyclo[6.6.6]eicosa-3,5,10,12,16,18-hexaeno(2-) iron(2+). Triethylamine (2 ml, 15 mmol) was added dropwise to the solution of BF3 O(C2H5)2 (1.9 ml, 15 mmol) in nitromethane (20 ml) with intensive stirring under argon. Then hexamethyldisiloxane (0.2 ml, 1 mmol), methylglyoxime (0.52 g, 5.1 mmol), complex [FeBd2(BF2)2(CH3CN)2] (3.48 g, 4.9 mmol) and nitromethane (10 ml) were added to the stirring reaction mixture. This mixture was heated to boiling, BF3O(C2H5)2 (0.6 ml, 5 mmol) was added and the solvent (23 ml) was partially distilled off for 1.5 h from the boiling reaction mixture (the reaction course was controlled by TLC; eluent: dichloromethane - hexane 1:2 mixture). Then this dark-red mixture was cooled to r.t., the precipitate formed was filtered off and washed with ethanol (30 ml, in three portions), diethyl ether (20 ml, in two portions), and hexane (10 ml). The product was extracted with dichloromethane (20 ml) and the extract was flash-chromatographed on silica gel (30 mm layer; eluent: dichloromethane). The major red elute was filtered, evaporated to a small volume and precipitated with hexane. The precipitate was filtered off, washed with hexane and dried in vacuo. Yield: 2.23 g (66 %). 1H NMR (CD2Cl2) 5 ppm: 2.37 (s, 3H, Me), 7.26 (m, 20H, Ph), 7.82 (s, 1H, HC=N). 13C{1H} NMR (CD2Cl2) 5 ppm: 14.10 (s, Me), 128.29, 129.41, 130.39, 130.79 (all s, Ph), 145.98 (s, HC=N), 154.11 (s, MeC=N), 156.09, 156.40 (both s, PhC=N).

R" =

0" a. o>. x-

CH3

X = CH3

n17H '""N^,

°/C2H5

C2HS CH3

Scheme 1.

Preparation of FeBd2(CH3Gm(diox))(BF)2: 1,8-bis(2-fluoro-bora)-2,7,9,14,15,20-hexaoxa-3,6,10,13,16,19-hexaaza-4,5,11,12-tetraphenyl-17-methyl-18-(1,4-dioxan-2-yl)bicyclo[6.6.6]eicosa-3,5,10,12,16,18-hexaeno(2-) iron(2+). Complex FeBd2Mm(BF)2 (0.123 g, 0.18 mmol) and FeSO47H2O (0.108 g, 0.39 mmol) were; dissolved/suspended in 1,4-dioxane (20 ml). 5M decane solution of tert-butyl hydroperoxide (0.24 ml, 1.2 mmol) was added and the reaction mixture was refluxed for 2.5 h. Then this mixture was cooled to room temperature, filtered and evaporated to dryness in vacuo. The oily residue was chromatographically separated on silica gel (230 - 400 mesh, 1x20 cm column, eluent: chloroform). The first minor elute, containing the clathrochelate precursor, was thrown out and the second elute was collected. This elute was evaporated to dryness, recrystallized from dichloromethane-heptane mixture (2:1 v/v) and dried in vacuo. Yield: 0.047 g (34 %). EI-MS: m/z Calcd. 778.1119; Found: 778.1671 (100 %); composition

found: C^HnO^N "B,F„56Fe,.

35 30 8 6 2

calcd: C„KrOiNB,KFe. 'H NMR

35 3U 8 6 2 2

(CD2Cl2) 5 ppm: 2.75 (s, 3H, Me), 3.69 (dd, 1H, 3-Hdiox), 3.79 (dd, 1H, 5-H.. ), 3.83 (dd, 1H, 5-H ), 3.91 (td, 1H, 6-h'°\ 3.98 (dd,

5 diox/5 v 5 5 diox/5 v 5 5 diox-" v 5

1H, 6-H ), 4.U2 (dd, 1H, 3-H ), 5.61 (dd, 1H, 2-H ), 7.35 (m,

5 diox/5 v 5 5 diox/5 v 5 5 diox-" v 5

2UH, Ph). 13C{1H} NMR (CD2Cl2) 5 ppm: 15.40 (s, Me), 66.72 (s, 5-C ), 67.41 (s, 3-C ), <57.(58 (s, 6-C ), 72.90 (s, 2-C ),

diox diox diox diox

128.40, 128.42 (two s, 3-Ph), 129.62, 129.64, 129.66 (all s, 1-Ph), 13U.5U, 130,53 (two s, 4-Ph), 130.94, 130.97, 131.00 (all s, 2-Ph), 155.47 (s, dioxC=N), 156.30 (s, MeC=N), 156.44, 156.54, 156.70 (all s, PhC=N). "B NMR (CD2Cl2) 5 ppm (JnB 19F): 3.61, 3.72 (two d, 16 Hz, O3BF). 19F NMR (CD2Cl2) 5 ppm: -169.40, -169.48 (two m, O3BF). IR (KBr) v cm-1: 694, 777, 939, 1000m, 1060, 1110 v(N -O), 1193m v(B - O)+v(B - F), 1545 v(dioxC=N), 1580 v(PhC=N)+(MeC=N). UV-Vis l nm (e10"3): 460 (21), 490 (9.5).

Results and Discussion

The monomethylglyoximate iron(II) clathrochelate FeBd2Mm(BF)2[21] (where Bd2- and Mm2- are a-benzildioxime and methylglyoxime dianions, respectively; refer to Experimental for enhanced synthetic protocol), with two unreactive a-benzildioximate chelate fragments and one substantially more reactive (under conditions of the Minisci reaction) methylglyoximate ribbed moiety, was

used as a macrobicyclic precursor (substrate). This allowed minimizing the number of the possible reactive sites of the substrate molecule and, thus, the range of the possible reaction products, as well as to compare the reactivity of its glyoximate (methine) oxime functional group and its methyl substituted analog. The Fenton-type Fe2+ - tert-butylhydroperoxide system was chosen for in situ generation of the reactive primary tert-butoxyl radicals:[6] they abstract hydrogen atom from 1,4-dioxane thus yielding the secondary 1,4-dioxan-2-yl radicals. These radicals further attack the glyoximate (methine) donor group of the macrobicyclic ligand, and the oxidation of the intermediate spin adduct by iron(III) ions completes this reaction (Scheme 2,i).

Mechanistically, the first stage of the above reaction is identical to that of the radical substitution of chlorine atom in a dichloroclathrochelate FeBd2(Cl2Gm)(BF)2 (where Cl2Gm2- is dichloroglyoxime dianion) with 1,4-dioxan-2-yl radical,[10] whereas the destinies of their intermediate spin adducts are different. Indeed, the chlorine atom, being a good leaving group, detaches from this intermediate giving the clathrochelate product FeBd2(ClGm(diox))(BF)2 (Scheme 2,ii). On the contrary, in accordance with the plausible Minisci reaction mechanism,[5] the methine hydrogen atom, that is a much worse leaving group, undergoes oxidation with iron(III) thus leading to the alkylated clathrochelate product FeBd2(CH3Gm(diox))(BF)2 and H+.

General view ofthe molecule FeBd2(CH3Gm(diox))(BF)2 (single crystal X-ray diffraction analysis, Table 1) is shown in Figure 1. The encapsulated iron(II) ion has a distorted trigonal-prismatic (TP) Fe^6-coordination polyhedron, characteristic of this type of the iron(II) clathrochelates and its average distortion angle j is equal to 23.5° (j=0° for an ideal TP and j=60° for an ideal trigonal antiprism (TAP)). The height h of this polyhedron is approximately 2.33 A and the Fe-N distances fall in the narrow range from 1.908 to 1.921 A. Other main bond lengths and angles in the macrobicyclic framework and those in the rib 1,4-dioxan-2-yl substituent have usual values.[22,23] This substituent adopts

fert-C4H9OOH +Fe"

FeBd2Mm(BF)2

ferf-C4H90' + Fe3+(OH)

- tert-C4H9OH

o.

FeBd2(CH3Gm(diox)(BF)2

N.....,\KI N. .CI

FeBd2(CI2Gm)(BF)2

0-

FeBd2(CH3Gm(diox)(BF)2

Scheme 2.

Using Minisci Reaction for Modification of the Tris-Dioximate Metal Clathrochelates

Figure 1. General view of the molecule FeBd2(CH3Gm(diox))(BF)2 Hydrogen atoms of the phenyl substituents are omitted for clarity.

a common chair conformation showing no signatures of a static disorder; it has a chiral center at the carbon atom attached to the clathrochelate framework. As this cage complex crystallizes in the chiral space group P212121, its crystal contains only one of the possible enantiomers.

It should be noted that all structurally characterized monosubstituted clathrochelates FeBd2(ClGmR))(BF)2 (where R are 1,4-dioxan-2-yl, tetrahydrofuran-2-yl or 1,3-dioxolan-2-yl substituents) reported in literature[10,11,13] and the clathrochelate under study are crystallized in this chiral space group, independently on the nature of a monofunctionalized cage molecule (i.e. is it chiral or not).

Multinuclear solution NMR study of the complex FeBd2(CH3Gm(diox))(BF)2 confirmed the identity of its molecular structure in solution and in solid state, while the above enantiomers of this clathrochelate, however, are indistinguishable by the NMR techniques applied. The complete assignment of the NMR signals for the molecule FeBd2(CH3Gm(diox))(BF)2 is given in Figure 2. Proton coupling constants and NMR shifts for the dioxanyl substituent are given in Table 2.

B 789F1

128.40 [l28.42|

129.62 129.64 129.66

1130.501

[13O.53J

130.94 130.97 131.00

B 3.61 ppm I 3.72 ppm F -169.40 ppm -169.48 ppm 1,T(BF) = 16 Hz

Figure 2. Assignment of the NMR signals for the molecule FeBd2(CH3Gm(diox))(BF)2.

Table 1. Crystallographic data and refinement parameters for the complex FeBd2(CH3Gm(diox))(BF)2CH2Cl2.

FeBd2(CH3Gm(diox))(BF)2CH2Cl2

C36H30B2Cl2F2FeN6O8

861.03 Orthorhombic

P 2 2 2

111

12.7423(4) 16.5899(5) 17.7248(5) 3746.9(2) 4

1.526 0.616 1760 0.28x0.20x0.14 2.02 - 27.53°

-16 < h < 15, -21 < k < 21, -15 < l < 22 27711 8611 (0.0435) 99.9 % (25.25°) 0.917 and 0.863 8611/0/503 1.054

Empirical formula Formula weight Crystal system Space group

a(A)

b(A) c(A) V(A3) Z

dcalc(g/cm3)

m (mm-1) F(000)

Crystal size (mm) Theta range for data collection

Index limits Reflections collected Independent reflections (Rint) Completeness to theta Max. and min. transmission Data/restraints/parameters Goodness-of-fit on F2 Final R indices (I>2oI) R indices (all data) Flack parameter Largest diff. peak and hole (e-A-3)

CCDC

R=0.0562, wR2=0.1403 R1=0.0633, wR2=0.1442 0.04(2) 1.156 and -1.505

1497026

Table 2. 1H-1H J-couplings and the positions of the 'H NMR signals of 1,4-dioxan-2-yl substituent in FeBd2(CH3Gm(diox))(BF)2 molecule.

H3

H3'

H5 H5'

H6

H6' 5 ppm

H2

H3

H3'

H5

H5'

H6

H6'

2.949

10.488 11.320

-11.76

0.818 2.793

2.717

5.607 4.016 3.687 3.828

11.749 3.778 -11.840 3.978 3.914

UV-Vis spectra of the initial complex FeBd2Mm(BF)2 and the clathrochelate product FeBd2(CH3Gm(diox))(BF)2 in the visible range are very similar and contain the intensive bands assigned to metal-to-ligand charge transfer Fed^Ln *. This similarity suggests that the above radical substitution of hydrogen atom by 1,4-dioxan-2-yl group only slightly affects the electronic structure of the quasiaromatic macro-bicyclic framework of these cage complexes.

Conclusions

Thus, we have shown that Minisci reaction can be successfully used for the rib functionalization of the tris-dioximate metal clathrochelates containing aldoxime groups. This extends the range of synthetic approaches applicable for the direct functionalization of these cage complexes.

Acknowledgements. This work was partly supported by RFBR (grants 14-03-00384, 16-03-00408). Y.Z.V also thanks the Russian Science Foundation (project 16-13-10475) for the financial support of the spectral part of this work.

References

1. Minisci F., Bernardi R., Bertini F., Gally R. Perchinummo M. Tetrahedron 1971, 27, 3575.

2. Minisci F., Citterio A. Acc. Chem. Res. 1983, 16, 27.

3. Minisci F., Vismara E., Fontana F. J. Org. Chem. 1989, 54, 5224.

4. Bolm C., Legros J., Le Paih J., Zani L. Chem. Rev. 2004, 104, 6217.

5. Li J.J. Name Reactions. A Collection of Detailed Mechanisms and Synthetic Applications, 5th ed. Springer, Heidelberg, New York, Dordrecht, London, 2014. p. 403-404.

6. Correa A., Fiser B., Gomez-Bengoa E. Chem. Commun. 2015, 51, 13365.

7. Minisci F., Vismara E., Fontana F., Radaelli D. Gazz. Chim. Ital. 1987, 117(5), 363.

8. Burdukov A.B., Vershinin M.A., Pervukhina N.V., Kozlova S.G., Eltsov I.V., Voloshin Y.Z. Russ. Chem. Bull., Int. Ed. 2011, 60, 2504.

9. Vershinin M.A., Burdukov A.B., Pervukhina N.V., Eltsov I.V., Voloshin Y.Z. Inorg. Chem. Commun. 2013, 30, 159.

10. Vershinin M.A., Burdukov A.B., Eltsov I.V., Reznikov V.A., Boguslavsky E.G., Voloshin Y.Z. Polyhedron 2011, 30, 1233.

11. Vershinin M.A., Burdukov A.B., Pervukhina N.V., Eltsov I.V., Voloshin Y.Z. Macroheterocycles 2012, 5, 11.

12. Vershinin M.A., Burdukov A.B., Pervukhina N.V., Eltsov I.V. J. Struct. Chem. 2015, 56, 379.

13. Vershinin M.A., Burdukov A.B., Pervukhina N.V., Eltsov I.V., Voloshin Y.Z. Macroheterocycles 2015, 8, 71.

14. Burdukov A.B., Vershinin M.A., Boguslavsky E.G., Eltsov I.V., Romanenko G.V., Belov A.S., Voloshin Y.Z. Inorg. Chem. Comm. 2013, 36, 117.

15. Burdukov A.B., Vershinin M.A., Pervukhina N.V., Eltsov I.V., Voloshin Y.Z. Curr. Inorg. Chem. 2015, 5, 71.

16. Armarego W.L.F., Chai C. Purification of Laboratory Chemicals, 6 ed, Oxford: Butterworth-Heinemann, 2009. 609 p.

17. SMART and SAINT, Release 5.0, Area detector control and integration software. Bruker AXS, Analytical X-Ray Instruments, Madison, Wisconsin, USA, 1998.

18. SADABS v.2.01, Bruker/Siemens Area Detector Absorption Correction Program, Bruker AXS, Madison, Wisconsin, USA, 1998.

19. Burla M.C., Caliandro R., Carrozzini B., Cascarano G.L., Cuocci C., Giacovazzo C., Mallamo M., Mazzone A., Polidori G. J. Appl. Cryst. 2015, 48, 306-309.

20. Sheldrick G.M., SHELX97 Release 97-2, University of Göttingen, Germany, 1998.

21. Voloshin Y.Z., Belov A.S., Starikova Z.A., Vologzhanina A.V. Russ. Chem. Bull., Int. Ed. 2013, 62, 1858.

22. Voloshin Y.Z., Antipin M.Yu. Russ. Chem. Bull., Int. Ed. 2004, 53, 2097.

23. Allen F.H., Kennard O., Watson D.G., Brammer L., Orphen A.G., Taylor R. Perkin Trans. II 1987, S1.

Received 29.11.2016 Accepted 14.12.2016

Макрогетероциклы /Macroheterocycles 2016 9(4) 413-417

417