PL218555B1 - New catalytic process for the preparation of basic (triorganosililo) alkynes - Google Patents

Description

The present invention relates to the selective preparation of (triorganosilyl) alkynes by silylating coupling of terminal alkynes with halogenotriorganosilanes.

The known methods of synthesizing substituted triorganosilylalkines can be divided into two groups: non-catalytic reactions and processes catalysed by transition metal complexes.

The first group includes mainly stoichiometric reactions of halogenotrganosilanes with lithium or magnesium compounds. The preparation of functionalized, substituted triorganosilylalkines based on the stoichiometric reactions of halosilanes with lithium or magnesium organo-alkynyl compounds enables the synthesis of a wide range of such compounds (1).

The introduction of an organosilyl substituent can also take place using lithium triorganosilylacetylide (Li + C CCCR ₃ ), reacting with appropriate alkyl aryl ketones to yield the functionalized substituted triorganosilylalkines (2).

Both methods require the use of highly reactive organometallic reagents (Li, Mg), which are expensive or unstable and must be synthesized just before the actual reaction, which makes it difficult to obtain the intended, substituted triorganosilylalkines, especially on a larger scale. The high reactivity of organometallic bonds of these metals results in the formation of a large amount of undesirable reaction products, reducing the yield of the main product (silylalkine) as well as hindering its isolation from the obtained reaction mixture.

Another group of methods enabling the synthesis of substituted triorganosilylalkines are direct silylation reactions of terminal alkynes in the presence of stoichiometric amounts of zinc salts (ZnCl2, Zn (OSO2CF3) 2). There are reactions of silylation of terminal alkynes with silylamines (3), chlorosilanes (4), and also trifluoromethylsulphonate (F3CS (O) 2OSiMe3) (5). These methods, although characterized by good yields and selectivity, require the use of at least equimolar amounts of zinc salt as an intermediate reagent, relative to the terminal alkyne, as well as very large, even 10-fold stoichiometric excesses of silylating reagents. In the case of chlorosilanes or F3CS (O) 2OSiMe3, it is also necessary to use tertiary amines which bind the hydrogen halide or trifluoromethylsulfonic acid released during the reaction.

Substituted triorganosilylalkines are obtained by reactions catalyzed with salts or complexes of transition metals. An example of the transition metal complex catalyzed preparation of substituted triorganosilylalkines can be the coupling reaction of triorganosilylethynyl lithium or magnesium with alkyl halides (6) or ethynyltrioragnosilane with or alkenyl or aryl halides in the presence of palladium (7) complexes. These methods are characterized by a large selectivity variability depending on the type of used reactants and catalysts, and amounting to no more than 80%. The actual reaction products are also accompanied by numerous by-products, including dimers of the starting alkynes, which make it difficult to isolate the silylalkynes from the reaction mixture and to purify them.

There are known methods of obtaining triorganosilylalkynes by reactions of terminal alkynes with trio-substituted silanes catalyzed by iridium complexes. (8). These methods use a dehydrogenative silylation reaction that produces a triorganosilyl functionalized alkyne and a variety of by-products. When using known iridium catalysts, the yield of the desired product does not exceed 40% due to the simultaneous progress of other competing reactions. Due to the complicated composition of the obtained post-reaction mixtures, the above method is of little practical importance.

Patent application WO 2008020774 discloses a method for the synthesis of substituted triorganosilylalkines by silylating coupling of vinyl-substituted silicon compounds and terminal alkynes in the presence of ruthenium (II) complexes. The process proceeds with good and high yields, but the desired products may be accompanied by homocoupling products of vinyl-substituted organosilicon compounds, which lowers the selectivity of the process. There is also a known method of synthesizing triorganosilyl-substituted alkynes in the process of cross metathesis of 1,2-bis (trimethylsilyl) ethyne with terminal alkynes in the presence of a uranium complex (9). Also in this case, apart from the main process, a number of undesirable side reactions take place, reducing the yield of triorganosilyl-substituted alkynes and hindering the operations related to their isolation and purification, which reduces the final efficiency of the process.

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Functionalized triorganosilylalkyls are also obtained by alkynylation of silylenolanes with chloroethynylsilane in the presence of gallium (III) chloride (10) or by reaction of aldimines with ethynyltrimethylsilane catalyzed by iridium (I) complexes (11). These processes, although they are characterized by high efficiency and selectivity of the obtained products, require specific substrates such as aldimines or unstable substituted chloroethynylsilanes, which limits the possibility of using this method for the synthesis of only some triorganosilylfunctionalized alkynes.

The aim of the invention was to develop a new method for the preparation of (triorganosilyl) alkynes.

It was surprisingly found that some of the iridium (I) complexes in the presence of a tertiary amine form an amine complex catalyzing the selective reaction of the silylating coupling of terminal alkynes with halosilanes, the product of which is (triorganosilyl) alkynes.

The process according to the invention for the preparation of (triorganosilyl) alkines of the general formula I, in which: R ¹ -CEC-SiR ² R ³ R ⁴ (1) ₁

- R ¹ is ferrocenyl, C1-5 alkyl, C5-7 cycloalkyl, aryl except heteroaryls, arylalkyl except heteroarylalkyl, alkylaryl where the alkyl chain contains C1-4 except alkylhete56roaryl, a silyl group of general formula 2 or a siloxy group of Formula 3 wherein R ⁵ and R ⁶ are C1-3 alkyl, aryl except for heteroaryls, or alkylaryl where the alkyl chain comprises C1-4 except for alkyl heteroaryls,

234

- R ^2, R ^3, R ⁴ are the same or different and represent alkyl, C1-5, cycloalkyl, C5-7, aryl, heteroaryl groups with the exception involves the reaction between the corresponding terminal alkyne of formula 4, wherein

R ¹ -CeCH (4) ₁

- R ¹ has the meanings given above and the corresponding halogenotriorganosilane of general formula 5 in which

X-SiR ² R ³ R ⁴ (5)

- X is Cl, Br, I, in particular iodine,

234

- R ² , R ³ , R ⁴ are as defined above, in the presence of a tertiary amine of the general formula 6, wherein

NO ⁷ R ⁸ R ⁹ (6)

- R ⁷ , R ⁸ , R ⁹ are equal or different and are C1-5 alkyl, C5-7 cycloalkyl, aryl except heteroaryls, arylalkyl where the alkyl chain contains C1-4 except heteroarylalkyl, alkylaryl where the alkyl chain contains C1-4 except for alkyl heteroaryls

And in the presence of a catalyst which is an iridium complex of general formula 7 in which

[{ir (g-Ci) (L)) d, (7)

- L is (cis, cis-1,5-cyclooctadiene), (CO) 2.

The complex [{ir (u.-Ci) (CO) ₂ ) 2l] is preferably used as catalysts. The catalyst is used in an amount of 0.01 to 4 mol% based on the terminal alkyne functional group, preferably in an amount of 0.5-1 moth%.

The reactions are carried out in an aromatic hydrocarbon solvent, preferably toluene, under an inert gas atmosphere.

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The tertiary amine used in the process according to the invention has a dual function, on the one hand, it acts as a co-catalyst that changes the structure of the starting iridium complex, and on the other hand, its excess binds the hydrogen halide released during the reaction.

In the process according to the invention, a tertiary amine of general formula 6 is introduced into a vigorously stirred suspension of the iridium complex of general formula 7 in a solvent at room temperature and mixed until the iridium complex, which acts as a precatalyst, is dissolved and the appropriate catalyst is formed with the tertiary amine. formula 8, where

[IrCl (L) (NR ⁷ R ⁸ R ⁹ )] (8)

L, R ^7, R ^8, R 9 are as defined above.

A suitable terminal alkyne of the general formula 4 and a triorganohalogenosilane of the general formula 5 are successively introduced into the thus prepared system, and then the reaction mixture obtained is heated to a temperature above 60 ° C but not higher than 140 ° C until the reaction is completed. ie until the starting terminal alkyne has reacted completely, followed by isolation and purification of the crude product.

The reaction takes place at any ratio of reactants, however, in the case of an unfavorable ratio, many by-products are formed. When equimolar amounts of terminal alkyne and halogenotriorganosilane are used, the selectivity of the process decreases and, in addition to the desired product, products of competing trimerization and oligomerization reactions of the starting alkyne are formed. If there is at least a 0.1 fold stoichiometric excess of a halogenotriorganosilane and a tertiary amine that binds the hydrogen halide in the form of the corresponding hydroammonium salt [HNR ⁷ R ⁸ R ⁹ ] X shifts the equilibrium of the reaction towards the correct product of general formula 1, thereby increasing the selectivity process. The reaction according to the invention is preferably carried out with a 0.4 - 0.6 fold molar excess of the halogenotriorganosilane and a 0.2 - 0.8 fold molar excess of the tertiary amine over the terminal alkyne. The reaction according to the invention is carried out in a temperature range of 60-140 ° C, optimally at 80 ° C. The reaction time is generally 24 hours.

The synthesis according to the invention is carried out in a moisture-proof reactor under an inert gas atmosphere, most preferably argon. The reactor is charged in the following order: catalyst, solvent, tertiary amine followed by terminal alkyne and halogenotriorganosilane. All liquid reactants as well as the solvent should be dehydrated and deoxygenated due to the sensitivity and possibility of decomposition of the catalyst and the starting halosilane in the presence of traces of water and oxygen. The reaction mixture is then heated and stirred until completion of the reaction.

Reversing the order of introducing the reactants, i.e. first the halogenotriorganosilane, then the terminal alkyne of general formula IV and last the tertiary amine of general formula VI, is also possible but may lead to a reduction in the selectivity of the process or complete blocking of the activity of the iridium catalyst system.

The crude product is isolated and purified by known methods. Generally, the isolation consists in evaporating the solvent from the reaction mixture, and then separating the crude product from the catalyst and the by-product of the hydrocarbon-ammonium halide formed as a by-product of the reaction, on a chromatographic column filled with silica gel or silica modified with 15% hexane Et3N solution, using aliphatic hydrocarbons as eluent, preferably hexane or pentane. Distillation under reduced pressure can also be a variant of isolation and purification of raw products.

The method of synthesis according to the invention, unlike the so far known methods described in the prior art, is a method in which the selectivity reaches the value of 99%, in which commonly available reagents are used, as well as small amounts of catalyst and much smaller stoichiometric excesses of halogenotriorganosilane and tertiary amine, calculated as on one alkyne group than in the known method described by Jiang.

The compounds obtained by the method of the invention are used as substrates for the synthesis of organic compounds derived from natural products with the possibility of their use in drug synthesis, as well as molecular compounds with a high degree of multiple bond coupling with precisely dedicated chemical, electronic and optoelectron properties for applications in the production of electronic components luminescent, photoluminescent or photosensors.

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The invention is illustrated in the examples which illustrate but do not limit the scope of the invention.

The identification of the products was made based on the results of the analysis:

13 29

- ¹ H, ¹³ C and ²⁹ Si NMR spectra which were recorded using Brucker spectrometers

Ultra Shield 600 MHz and Varian Mercury VT 400 MHz.

- elementary, which were made with the Vario EL Elemantar camera

Table 1 summarizes the elemental and NMR analysis data

P r z k ł a d 1

In a 40 mL reactor equipped with a magnetic stirrer, 0.0085 g (0.015 mmol) [{Ir (α-Cl) (CO) ₂ } ₂ ] were placed under argon, followed by 8 mL of anhydrous and deoxygenated toluene and 0.7 g (5.4 mmol) NEt (i-Pr) 2. The mixture was stirred until the starting iridium (I) complex was dissolved, and then 0.306 g (3 mmol) of phenylacetylene and 0.96 g (4.8 mmol) of ISiMe3 were introduced into the mixture obtained. The reaction was carried out at 80 ° C until the phenylacetylene was completely converted. After completion of the reaction, in order to remove the catalyst from the reaction mixture, the solvent and the remains of unreacted reactants were evaporated under reduced pressure, and then the residue was applied to a chromatographic column filled with silica gel and the product was isolated using hexane as eluent. The solvent was pre-evaporated from the eluate and the remaining product was distilled by trap-to-trap technique under reduced pressure. 0.47 g of phenylethynyltrimethylsilane is obtained with a yield of 90%.

P r z k ł a d 2

Proceeding as in example 1, the reactions between:

- 0.475 g (3 mmol) of 4-t-Bu-phenylacetylene

- 0.96 g (4.8 mmol) ISiMe3 in the presence of:

- 0.0085 g (0.015 mmol) of the complex [{Ir (g-Cl) (CO) 2h]

- 0.70 g (5.4 mmol) NEt (i-Pr) 2

0.59 g of 1- (4-t-Bu-phenyl) -2-trimethylsilylethyne was obtained in a yield of 85%.

P r z k ł a d 3

Proceeding as in example 1, the reactions between:

- 0.511 g (3 mmol) HCECC (Me) (Et) (OSiMes)

- 0.96 g (4.8 mmol) ISiMe3 in the presence of:

- 0.017 g (0.03 mmol) of the complex [{Ir (u-Cl) (CO) 2} 2]

- 0.70 g (5.4 mmol) NEt (i-Pr) 2

0.68 g of 1-trimethylsilyl-3-methyl-3-trimethylsiloxy-1-butyne is obtained in a yield of 94%.

P r z k ł a d 4

Proceeding as in example 1, the reactions between:

- 0.393 g (2 mmol) of 1-ethynyl-1-trimethylsiloxy-cyclohexane

- 0.64 g (3.2 mmol) of ISiMe3 in the presence of:

- 0.0113 g (0.02 mmol) of the complex [{Ir (u-Cl) (CO) 2} 2]

- 0.47 g (3.6 mmol) NEt (i-Pr) 2

0.51 g of 1-trimethylsilylethynyl-1-trimethylsiloxy-cyclohexane is obtained in a yield of 95%.

P r z k ł a d 5

In a 30 mL reactor equipped with a magnetic stirrer under argon, 0.0113 g (0.02 mmol) of the complex [{Ir (α-Cl) (CO) ₂ } ₂ ], 10 mL of toluene and 0.827 g (6, 4 mmol) NEt (i-Pr) 2. The mixture was stirred until the starting iridium (I) complex had dissolved, and then 0.248 g (2 mmol) of 1-ethynyl-1-hydroxy-cyclohexane was introduced. In the next step, 1,200 g (6 mmol) of ISiMe3 were slowly introduced at room temperature, after which the mixture was heated to 80 ° C while being vigorously stirred. The reaction was carried out until the starting alkyne was completely converted. After completion of the reaction, the solvent and unreacted starting materials were evaporated under reduced pressure. The silylation product was extracted with pentane using a filter tube. The solvent was pre-evaporated from the extract and the crude product was purified on a SiO2 column (modified with 15% hexane Et3N) using hexane as the eluent. 0.52 g of 1-trimethylsilylethynyl-1-trimethylsiloxy-cyclohexane is obtained in a yield of 91%.

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P r z k ł a d 6

Proceeding as in example 1, the reactions between:

- 0.561 g (2 mmol) of 3,3-diphenyl-3-trimethylsiloxy-1-propyne

- 0.64 g (3.2 mmol) of ISiMe3 in the presence of:

- 0.0113 g (0.02 mmol) of the complex [{Ir (g-Cl) (CO) 2h]

- 0.47 g (3.6 mmol) NEt (i-Pr) 2

0.67 g of 1-trimethylsilyl-3,3-diphenyl-3-trimethylsiloxy-1-propyne is obtained with a yield of 95%. P r z k ł a d 7

Proceeding as in example 1, the reactions between:

- 0.42 g (2 mmol) of ethynylpherocene

- 0.64 g (3.2 mmol) of ISiMe3 in the presence of:

- 0.0113 g (0.02 mmol) of the complex [{Ir ^ -Cl) (CO) 2} 2]

- 0.47 g (3.6 mmol) NEt (i-Pr) 2

0.51 g of 1-ferrocenyl-2-trimethylsilylethyne was obtained with a yield of 90%.

P r z k ł a d 8

Proceeding as in example 1, the reactions between:

- 0.363 g (2 mmol) HC = CSi (/ - Pr) 3

- 0.64 g (3.2 mmol) of ISiMe3 in the presence of:

- 0.0113 g (0.02 mmol) of the complex [{Ir4 -Cl) (CO) 2h]

- 0.47 g (3.6 mmol) NEt (/ - Pr) 2

0.49 g of 1- (tri-iso-propylsilyl) -2-trimethylsilylethyne is obtained with a yield of 97%.

P r z k ł a d 9

Proceeding as in example 1, the reactions between:

- 0.32 g (2 mmol) HCeCSiMe ₂ Ph

- 0.64 g (3.2 mmol) of ISiMe3 in the presence of:

- 0.0113 g (0.02 mmol) of the complex [{Ir ^ -Cl) (CO) ₂ } ₂ ]

- 0.47 g (3.6 mmol) NEt (/ - Pr) 2

0.44 g of 1-Dimethylphenylsilyl-2-trimethylsilylethyne is obtained with a yield of 95%.

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Table 1 Characterization of the compounds obtained in individual examples.

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Literature

1. W.P. Weber, Silicon Reagents for Organic Synthesis, Springer-Verlag, Berlin, 1983, 129-158

2. M. Bolourtchian, R. Zadmard, M.R. Saidi, Monatshefte fufChemie 1999, 130, 333-336

3. A.A. Anreev, V.V. Konshin, N.V. Komarov, M. Rubin, Ch. Brouwer, V. Gevorgyan, V. Org. Lett. 2004, 6, 421-424

4. H. Jiang, S. Zhu, S. Tetrahedron Lett. 2005, 46, 517-519

5. R.J. Rahaim Jr., J.T. Shaw, J. Org. Chem. 2008, 73, 2912-2915

6. L.-M. Yang, L.-F. Huang, T.-Y. Luh, Org. Lett. 2004, 6, 1461-1463

7. S. Takahashi, Y. Kuroyama, K. Sonogashira, N. Hagihara, Synthesis, 1980

8. B. Marciniec, I. Kownacki Transformations of (organo) siliocon compounds catalyzed by iridium complexes in Iridum Complexes in organic synthesis (Luis A. Oro, Carmen Claver, eds.), Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2009, chapter 14, pp. 345-367

9. J. Wang, Y. Gurevich, M. Botoshansky, M.S. Eisen, J. Am. Chem. Soc. 2006, 128, 9350-9351

10. R. Amemiya, M. Yamaguchi, Eur. J. Org. Chem. 2005, 5145-5150

11. Ch. Fischer, E.M. Carreira, Organic Letters, 2001, 3, 4319-4321

Claims (4)

A method for the preparation of (triorganosilyl) alkynes of general formula I wherein R ¹ -CEC-SiR ² R ³ R ⁴ (1) ₁ - R ¹ is ferrocenyl, C1-5 alkyl, C5-7 cycloalkyl, aryl except heteroaryls, arylalkyl except heteroarylalkyl, alkylaryl where the alkyl chain contains C1-4 except alkylhete56roaryl, a silyl group of general formula 2 or a siloxy group of Formula 3 wherein R ⁵ and R ⁶ are C1-3 alkyl, aryl except for heteroaryls, or alkylaryl where the alkyl chain comprises C1-4 except for alkyl heteroaryls, R ⁵ Snr ⁵ R ⁵ _x R ⁶ O-Si ^ _R 6 R ⁶ (2) (3) 234 - R ^2, R ^3, R ⁴ are the same or different and represent alkyl, C1-5, cycloalkyl, C5-7, aryl, except for heteroaryls, characterized in that it consists in the reaction between the corresponding terminal alkyne of formula 4, which R ¹ -CeCH (4) ₁ - R ¹ has the meanings given above and the corresponding halogenotriorganosilane of general formula 5 in which X-SiR ² R ³ R ⁴ (5) - X is Cl, Br, I, in particular iodine, 234 - R ² , R ³ , R ⁴ are as defined above, in the presence of a tertiary amine of the general formula 6, wherein NO ⁷ R ⁸ R ⁹ (6) - R ⁷ , R ⁸ , R ⁹ are the same or different and are C1-5 alkyl, C5-7 cycloalkyl, aryl except heteroaryls, arylalkyl where the alkyl chain contains C1-4 except heteroarylalkyl, alkylaryl where the alkyl chain contains C1- 4 with the exception of alkylheteroaryls and in the presence of a catalyst which is an iridium complex of the general formula in which [{ir (g-Ci) (L)) 2j, (7) PL 218 555 B1 - L is (cis, cis-1,5-cycloactadiene), (CO) 2; the process is carried out in an anhydrous and anaerobic atmosphere. 2. The method according to p. The process of claim 1, wherein the catalyst is used in an amount of 0.01 to 4 mol% relative to the terminal alkyne functional group. 3. The method according to p. 2. The process of claim 2, wherein the catalyst is used in an amount of 0.5-1 mol% with respect to the terminal alkyne functional group. 4. The method according to p. A process as claimed in any one of the preceding claims, wherein the catalysts are the complex [{Ir1 -C2O2].