Synthesis of Derivatives of closo-Dodecaborate Anion Based on Amino Acid Esters

This work proposes a new method for the synthesis of N-borylated amino acids based on nucleophilic substitution reactions in the [B12H11IPh]– anion. Esters of glycine and L-phenylalanine were used as nucleophiles. The structure of the products has been determined by multinuclear NMR spectroscopy, IR spectroscopy, and ESI mass spectrometry.

The main interest of researchers is focused on the development of methods for the directed functionalization of boron cluster anions. Thus, along with the processes of electrophilic [19][20][21] and nucleophilic substitution [22,23] of hydrogen atoms in the boron cluster, the process of ipso-substitution [24][25][26] can be considered as an effective method of functionalization.
Halonium ions are one of the types of such groups, which can react with a number of nucleophilic reagents. This approach was successfully extended to iodonium derivatives of carboranes [27], which react with various nucleophiles with selective substitution of the arylgalonium substituent. Monocarboranes and boron cluster anions have a negative charge, and aryliodonium zwitterions based on them differ from derivatives of neutral carboranes in terms of reactivity and selectivity of the processes. The preparation of derivatives of hypervalent iodine through the oxidation of iodo-closo-borates is described in the literature [28]. It should be noted that this approach has a number of disadvantages, since it leads to the formation of oxidation products of the cluster fragment. The use of hypervalent iodine compounds can significantly increase the yield of target closo-borates [29,30]. Iodonium derivatives can enter into substitution reactions of PhI groups with a number of nucleophiles (pyridines, thioureas, cyanide ion, azide ion, etc.) [31][32][33][34][35]. In [36,37], the possibility of using phenyliodonium derivatives of the closo-dodecaborate anion and substituted analogs for the targeted introduction of various functional groups into the cluster was shown.
Thus, the use of iodonium functional substituents as leaving (ipso) groups is a rather powerful tool for creating new boron-containing compounds with a given set of properties. In this regard, the aim of this work was the creation of new substituted derivatives of the closo-dodecaborate anion and natural amino acids based on the processes of nucleophilic substitution in the [B 12  IR spectra of the synthesized compounds were recorded on an Infralum FT-08 IR Fourier spectrom-

SYNTHESIS AND PROPERTIES OF INORGANIC COMPOUNDS
eter (NPF AP Lumex) in the range 4000-400 cm -1 with a resolution of 1 cm -1 . Samples were prepared as potassium bromide pellets. 1 H, 11 B, and 13 C NMR spectra of solutions of the investigated substances in CD 3 CN were recorded on a Bruker Avance II-300 spectrometer at frequencies of 300.3, 96.32, and 75.49 MHz, respectively, with internal deuterium stabilization. Tetramethylsilane or boron trifluoride etherate were used as external standards.
ESI mass spectra of solutions of the investigated substances in CH 3 CN were recorded on a Bruker MicrOTOF-Q spectrometer (Bruker Daltonik, Germany). Ionization conditions: Apollo II electrospray ionization source, ion spray voltage +(-)4500 V, temperature 200°C, flow 3 μL/min. Tetraphenylphosphonium phenyliodododecaborate (Ph 4 P)[B 12 H 11 IPh]. Acetonitrile (15 mL) and trifluoroacetic acid (2 mL) were added to (Ph 4 P) 2 [B 12 H 12 ] (2.0 g, 2.4 mmol). PhI(OAc) 2 (0.77 g, 2.4 mmol) was added to the resulting solution, and the reaction mixture was stirred in an atmosphere of dry argon with moderate heating (up to 40°C) for 2 h. After that, the solution was concentrated on a rotary evaporator and the product was recrystallized from a mixture of acetonitrile and diethyl ether. The resulting solid was washed with glacial acetic acid and diethyl ether, then dried under oil pump vacuum. Yield, 1.45 g (88%). Derivative of glycine ethyl ester (Ph 4 P)[B 12 H 11 NH 2 CH 2 COOEt]. A mixture of (NH 2 CH 2 COOEt)·HCl (0.47 g, 3.4 mmol) and 4-dimethylaminopyridine (0.43 g, 3.4 mmol) in anhydrous tetrahydrofuran (THF, 20 mL) was prepared. The resulting suspension was stirred in a dry argon atmosphere at room temperature until complete precipitation of dimethylaminopyridinium hydrochloride (~0.5 h). The precipitate was filtered off, and (Ph 4 P)[B 12 H 11 IPh] (0.50 g, 0.7 mmol) was added to the mother solution. The resulting reaction mass was heated at 80°C for 4 h in a dry argon atmosphere. After the completion of the reaction, the resulting solution was evaporated on a rotary evaporator, and the solid residue was recrystallized from a mixture of methanol and diethyl ether. The resulting powder was dissolved in dichloromethane and washed with a 0.1 M HCl solution. The organic phase was separated, washed with water until neutral pH, dried over anhydrous sodium sulfate, and then concentrated on a rotary evaporator. The product was dried under vacuum. Yield, 0.29 g (70%).
Since the amino acid esters in the form of free bases are unstable, we used the corresponding hydrochlorides. In this case, the deprotonated forms of esters were obtained in situ under the action of organic bases in the medium of tetrahydrofuran (THF). The use of triethylamine as a base led to the formation of a significant amount of the chlorination byproduct of the closo-dodecaborate anion, which is obviously related to the solubility of the hydrochloride in THF. Therefore, we decided to use 4-dimethylaminopyridine as a base; its hydrochloride is easily removed from the reaction mixture by filtration.
The addition of the ester of (Ph 4 P)[B 12 H 11 IPh] to the solution results in the substitution of the phenyliodonium group for the amino acid residue. The reaction takes place already at room temperature, but the rate of this process is low. Heating the reaction mixture to 80°C makes it possible to achieve complete conversion of the initial iodonium derivative in 4 h. It should be noted that the studied process is sensitive to the presence of water and chloride ions in the system, which leads to side processes and reduces the yield of the target product.
The reaction progress was monitored on the basis of 11 B NMR spectroscopy data. Thus, the 11 B NMR spectra of the target ammonium-type derivatives contain two signals in the range -7.2…-7.7 ppm (s, 1B, B-N) and -16.5…-16.8 ppm (m, 11 B, B-H). The introduction of a more electronegative ammonium group leads to a shift of the signal from the substituted boron atom to a weaker field as compared to the spectrum of the initial iodonium derivative.
The structure of functional groups in the obtained products was determined using 1 H and 13 C NMR spectroscopy. Thus, in the 1 H NMR spectrum of compound (Ph 4 P)[B 12 H 11 NH 2 CH 2 COOEt] along with the signals of the cation protons, the signals of the protons of the amino acid residue are observed. The ammonium group is represented by a broadened singlet at 6.86 ppm (2H, NH 2 ), the protons of the methylene group appear as a doublet at 3.99 ppm (2H, CH2COO, J = 6 Hz). This signal splitting is typical of amino acid derivatives with a rigid spatial structure [38]. The 13     were obtained based on the processes of nucleophilic substitution of the phenyliodonium substituent under the action of ethyl esters of amino acids.

ACKNOWLEDGMENTS
The NMR spectra of the obtained samples were recorded using the equipment of the Center for Collective Use of the Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, which functions with the support of the State Assignment of the Kurnakov Institute, Russian Academy of Sciences in the field of fundamental scientific research.

FUNDING
This work was supported by the Russian Science Foundation (grant no. 18-73-10092).

CONFLICT OF INTEREST
The authors declare that they have no conflicts of interest.

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