Received: July 2020

DOI 10.17677/fn20714807.2020.04.01

Fluorine Notes, 2020, 131, 1-2

A NOVEL REDUCTION REACTION FOR THE CONVERSION OF TRIBUTYL(TRIFLUOROMETHYL)STANNANE INTO TRIBUTYL(DIFLUOROMETHYL)STANNANЕ

Alexander S. Golubev, Petr N. Ostapchuk

A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilov St. 28, 119991, GSP-1, Moscow, Russian Federation

E-mail: golubev@ineos.ac.ru

Abstract: A new method for obtaining tributyl(difluoromethyl)stannane n-Вu₃SnCF₂H by reduction of n-Вu₃SnCF₃ with lithium borohydride in diglyme has been developed.

Keywords: tributyl(difluoromethyl)stannanе, tributyl(trifluoromethyl)stannane, lithium borohydride, reduction.

The introduction of a difluoromethyl group into organic molecules is often used in the development of new pharmaceuticals and agrochemicals [1]. Several years ago, a method for difluoromethylation of aryl, heteroaryl and β-styryl iodides using tributyl(difluoromethyl)stannane n-Bu₃SnCF₂H was developed. The synthesis of n-Bu₃SnCF₂H was accomplished by the reaction of tributyltin hydride with trifluoromethyltrimethylsilane Me₃SiCF₃, with column chromatography being used to purify n-Bu₃SnCF₂H [2].

As part of an ongoing project on the synthesis of difluoromethyl-containing physiologically active compounds, we needed n-Вu₃SnCF₂H free of n-Bu₃SnCF₃. In experiments on the synthesis of n-Bu₃SnCF₂H according to the protocol given in [2], we have always observed the formation of tributyl(trifluoromethyl)stannane n-Bu₃SnCF₃ as a by-product. Column chromatography could indeed significantly reduce the content of n-Bu₃SnCF₃ impurity. Nevertheless, it was possible to completely get rid of n-Вu₃SnCF₃ only at the expense of a significant loss of the target n-Вu₃SnCF₂H. To obtain n-Вu₃SnCF₂H not containing n-Вu₃SnCF₃, we have developed a new reduction reaction for the conversion of n-Вu₃SnCF₃ to n-Вu₃SnCF₂H.

We found that tributyl(trifluoromethyl)stannane n-Вu₃SnCF₃ reacted with lithium borohydride LiBH₄ in diglyme to form tributyl(difluoromethyl)stannane n-Вu₃SnCF₂H (scheme 1).

Scheme 1.

Application of 1.5 equivalents of LiBH₄ and moderate heating (60 °C) brought about a complete conversion of the starting n-Вu₃SnCF₃ and a good yield of the target n-Вu₃SnCF₂H (60-70%) in a reasonable time (24 h). The formation of n-Вu₃SnCF₂H was also observed at room temperature, but the conversion did not exceed 50% in 24 hours. The completion of the reaction was monitored by ¹⁹F{¹H} NMR spectroscopy (n-Вu₃SnCF₃ showed a singlet at -45.13 ppm with ¹¹⁹Sn satellites: ²J (¹⁹F,¹¹⁹Sn) = 214 Hz; n-Вu₃SnCF₂H showed a singlet at -124.62 ppm with ¹¹⁹Sn satellites: ²J (¹⁹F,¹¹⁹Sn) = 212 Hz) and ¹¹⁹Sn NMR spectroscopy (a quartet with at -22.7 ppm with a coupling constant ²J (¹⁹F,¹¹⁹Sn) = 218 Hz for n-Вu₃SnCF₃; a triplet at -49.4 ppm with a coupling constant ²J (¹⁹F,¹¹⁹Sn) = 214 Hz for n-Вu₃SnCF₂H).

The main byproduct of the reaction was bis(tributyltin) oxide. Its formation apparently occurs due to traces of water in the reagents (LiBH₄ is extremely hygroscopic).

Only one hydride ion of the LiBH₄ molecule was involved in the reduction reaction. Since diborane was released during the reaction, the reduction process had to be carried out under a continuous flow of nitrogen flow. The gas stream leaving the reaction vessel was bubbled through a column of water or acetone.

By the end of the reaction, clear partitioning of the reaction solution into two phases was observed. The study of the phases showed that n-Вu₃SnCF₂H was almost completely in the lower phase. Unreacted LiBH₄ and the remaining diborane were in the upper phase. Their interaction, as is known [3,4], leads to the formation of LiB₂H₇. Lithium diborohydride binds diglyme (DG) in the form of a solvate complex of the LiB₂H₇2DG structure, which was apparently the reason for partitioning of the reaction solution.

Treatment of the reaction with water required special attention. It is recommended to pour the reaction into ice water. Adding water to the reaction in one of the experiments caused a vigorous reaction, which led to the splashing of the contents of the reaction flask.

Our attempts to use sodium borohydride NaBH₄ in diglyme for the reduction of n-Вu₃SnCF₃ by analogy with the reduction of trifluoromethyltrimethylsilane Me₃SiCF₃ to difluoromethyltrimethylsilane Me₃SiCF₂H [5] met no success. We observed the formation of n-Вu₃SnCF₂H, however, we failed to achieve a significant conversion in the temperature range of 20-50 °C. Interestingly, when reducing Me₃SiCF₃ to Me₃SiCF₂H with sodium borohydride, at least 3 hydride ions of the NaBH₄ molecule are involved in the process [5].

Thus, we have developed a new method for obtaining tributyl(difluoromethyl)stannane
n-Вu₃SnCF₂H by reduction of n-Вu₃SnCF₃ with lithium borohydride in diglyme. The new method avoids the use of unsafe and prone to oxidation tributyltin hydride. An advantage of the method is the possibility of obtaining Вu₃SnCF₂H that does not contain n-Вu₃SnCF₃.

Experimental part

¹H, ¹⁹F, ¹¹⁹Sn NMR spectra were recorded on a Bruker Avance^TM400 spectrometer (400.13 MHz for ¹H, 376.50 MHz with proton decoupling for ¹⁹F, 149.21 MHz for ¹¹⁹Sn). The proton chemical shifts were measured relative to the residual solvent signal (δ (CDCl₃) 7.28 ppm) and recalculated from the SiMe₄ signal. The ¹⁹F NMR chemical shifts were measured relative to trifluoroacetic acid (an internal standard) and referenced to CFCl₃. ¹¹⁹Sn NMR chemical shifts were determined relative to Me₄Sn as an internal standard (δ 0.0 ppm).

Tributyl(trifluoromethyl)stannane n-Вu₃SnCF₃ was prepared from bis(tributyltin) oxide and trifluoromethyltrimethylsilane Me₃SiCF₃ according to the procedure described in [6].

The reaction was carried out in a 3-necked round bottom flask under a stream of dry nitrogen. The flask was equipped with a dry nitrogen inlet tube, a dropping funnel and an outlet connected to an absorption column with water or acetone. To a solution of 7.0 g (19.5 mol) tributyl(trifluoromethyl)stannane in 30 ml of dry diglyme was added lithium borohydride (0.64 g, 29.3 mmol) as a solution in diglyme (9.8 ml of a 3M solution in diglyme). The addition of LiBH₄ was accompanied by a rapid rise in the temperature of the reaction mixture to 35 °C. The reaction mixture was heated with stirring at 60 °C for 24 hours. Reaction control (¹⁹F NMR) showed complete conversion of the starting n-Вu₃SnCF₃. The reaction was poured into ice water (200 ml), extracted with toluene (50 ml + 30 ml). The combined organic phases were evaporated in vacuo on a rotary evaporator. The residue was distilled, and 4.2 g (63%) of the liquid with b.p. 89-93 °C/0.3 Torr was obtained, which was tributyl(difluoromethyl)stannane n-Вu₃SnCF₂H and about 6 mol. % diglyme. Tributyl(difluoromethyl)stannane n-Вu₃SnCF₂H can be further purified through a small pad of silica gel, eluent petroleum ether: ethyl acetate 100: 1, to detect cerium molybdate (Hanessian's Stain).

¹H NMR (CDCl₃) δ 6.45 (t, J = 44.9 Hz, 1H), 1.70 – 1.44 (m, 6H), 1.44 – 1.24 (m, 6H), 1.21 – 0.97 (m, 6H), 0.93 (t, J = 7.3 Hz, 9H).

¹⁹F{¹H} NMR (CDCl₃) δ -124.62 s with ¹¹⁹Sn satellites: ²J (¹⁹F,¹¹⁹Sn) = 212 Hz).

¹¹⁹Sn NMR (CDCl₃) δ -51.94 (t, J = 214.4 Hz) (see, also [2]).

Acknowledgments

This work was performed with the financial support from Ministry of Science and higher Education of the Russian Federation using the equipment of Center for molecular composition studies of INEOS RAS.

Literature

1. Yerien D. E., Barata‐Vallejo S., Postigo A., Difluoromethylation reactions of organic compounds, Chemistry–A European J., 2017, 23(59), 14676-14701.
2. Prakash G. K. S., Ganesh S. K., Jones J.-P., Kulkarni A., Masood K., Swabeck J. K., Olah G. A. Copper‐mediated difluoromethylation of (hetero)aryl iodides and β‐styryl halides with tributyl(difluoromethyl)stannane, Angewandte Chemie, 2012, 124(48), 12256-12260.
3. Brown H. C., Stehle P. F., Tierney P. A., Singly-bridged compounds of the boron halides and boron hydrides., J. Am. Chem. Soc., 1957, 79(8), 2020-2021.
4. Titov L. V., Gavrilova L. A., Borohydrides of the alkali and alkaline-earth metals., Russ. Chem. Bull., 1976, 232-235.
5. Tyutyunov A. A., Boyko V. E., Igoumnov S. M. The unusual reaction of (trifluoromethyl)-trimethylsilane with sodium borohydride., Fluorine Notes, 2011, Vol. 1(74).
6. Prakash G. K. S., Yudin A. K., Deffieux D., Olah G. A., Synthetic methods, Part 197, Facile preparation of (trifluoromethyl)tributyltin and transtrifluoromethylation of disilyl sulfides to the corresponding trifluoromethylsilanes, Synlett, 1996, 2, 151-153.

ARTICLE INFO
Received 14 July 2020
Accepted 15 July 2020
Available online August 2020

Recommended for publication by Prof. S.M. Igumnov

Fluorine Notes, 2020, 131, 1-2