- Email: [email protected]
Pt-catalyzed O-silylation of oximes by tri-substituted organosilanes
Tetrahedron Letters 60 (2019) 1636–1639
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Pt-catalyzed O-silylation of oximes by tri-substituted organosilanes Shreeja V. Bhatt a, Shreya V. Bhatt a, Jean Fotie a,⇑ a
Department of Chemistry and Physics, Southeastern Louisiana University, SLU 10878, Hammond, LA 70402-0878, United States
a r t i c l e
i n f o
Article history: Received 30 March 2019 Revised 16 May 2019 Accepted 17 May 2019 Available online 23 May 2019 Keywords: O-silylation Speier’s catalyst Oximes Trisubstituted-hydrosilanes
a b s t r a c t Silylated derivatives of oximes are important intermediates in organic synthesis, and have found application in the preparation of various nitrogen containing compounds including nitriles, amines, nitrones, and hydroxylamines. An efficient method for the O-silylation of aldoximes and ketoximes through a platinum-catalyzed reaction using trisubstituted-hydrosilanes is described. The reaction works well with a range of aliphatic and aromatic oximes when using triethylsilane as a silylating agent. Furthermore, a number of tri-substituted organosilanes including triisopropylsilane, diethoxymethylsilane, triphenylsilane, and triethoxysilane were also explored. Ó 2019 Elsevier Ltd. All rights reserved.
Introduction O-silylation is a well-established strategy for functional group protection in multi-step organic syntheses, and has primarily been used for the protection of hydroxyl groups of alcohols, phenols, and carboxylic acids [1]. However, O-silylated aldoximes and ketoximes have progressively established themselves as important intermediates in the synthesis of nitriles [2], amines [3], nitrones [4], and hydroxylamines [5]. They have also found application in the synthesis of a-alkylsilylated oximes via O-silylated derivatives followed by the migration of the alkylsilyl group [6], as well as in the preparation of a-hydroxy-substituted oxime ethers by enantioselective Si–O coupling reactions [7]. As such, the preparation of O-silylated aldoximes and ketoximes has received a great deal of attention over the years. In general, O-silylated oximes are synthesized either by heating an oxime at reflux with hexamethyldisilazane (HMDS) [4a,8] or triethylsilanamine (Et3SiNH2) [9] in the presence of a catalyst, or by reacting it with trialkylchlorosilane in the presence of bases such as trimethylamine [10], imidazole [11] or NaH [12]. These latter silylating methods have been reported as sluggish, and often require an excess of chlorosilane and a stoichiometric amount of the base. [11a,c,d,13] There have also been a handful of reports on the preparation of silyl ethers of oximes using trialkylatedhydrosilanes in the presence of piperidine [14], 1,3-diisopropyl4,5-dimethylimidazol-2-ylidene [15], InBr3 [16] or fluorine [17]. With the above in mind, upon unexpectedly discovering that Speier’s catalyst (H2PtCl66H2O in isopropanol) could catalyze the ⇑ Corresponding author. E-mail address: [email protected] (J. Fotie). https://doi.org/10.1016/j.tetlet.2019.05.033 0040-4039/Ó 2019 Elsevier Ltd. All rights reserved.
O-silylation of 4-methylbenzaldehyde oxime in the presence of triethylsilane, it seemed appropriate to further explore the reaction as it could be of interest in organic synthesis.
Results and discussion Speier’s catalyst (H2PtCl66H2O in isopropanol) has been used for hydrosilylation reactions since the 1950s [18]. It was during a comparative analysis between Speier’s catalyst and Pt(0) nano-dispersed in a range of organically modified silicates as catalysts for hydrosilylation reactions [19], that we noted H2PtCl66H2O was able to catalyze the O-silylation of 4-methylbenzaldehyde oxime in the presence of triethylsilane, as illustrated in Scheme 1. An exploration of the reaction conditions was undertaken, and a number of solvents including toluene, acetonitrile, dichloromethane, 1,4-dioxane and THF were investigated. The catalyst loading was optimized, and the results are summarized in Table 1. As already mentioned, this reaction was discovered during a comparative analysis between Speier’s catalyst and Pt(0) nano-dispersed in a range of organically modified silicates as catalysts for
Scheme 1. O-silylation of 4-methylbenzaldehyde oxime in the presence of H2PtCl66H2O.
1637
S.V. Bhatt et al. / Tetrahedron Letters 60 (2019) 1636–1639 Table 1 Exploration of the reaction conditions using 4-methylbenzaldehyde oxime and triethylsilane. Entries
Et3SiH (eq.a)
H2PtCl66H2O (mol%)
Solvent
Temperature
Time (h)
Percent conversion (%)b
1 2 3 4 5 6 7 8 9 10 11 12
1.2 2 1 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2
0.01 0.01 0.01 0.005 None 0.01 0.01 0.01 0.01 0.01 0.01 0.01
Toluene Toluene Toluene Toluene Toluene Toluene Toluene Toluene CH3CN CH2Cl2 1,4-Dioxane THF
Reflux Reflux Reflux Reflux Reflux Rt 100 °C Reflux Reflux Reflux Reflux Reflux
18 18 18 18 18 18 18 6 18 18 18 18
95c 94c 82 62 NRd NRd 78 67 Trace NRd Trace NRd
Reactions were performed under a nitrogen atmosphere, using 100 mg of 4-methylbenzaldehyde oxime. a In relationship to the number of moles of 4-methylbenzaldehyde oxime. b Percent conversions determined by GC–MS, using tridecane as an internal standard. c No starting material was present upon reaction completion as indicated by the GC–MS spectrum. d N.R. = No Reaction.
the hydrosilylation reactions [19], and as such, the initial conditions (Entry 1) were carried over from these aforementioned studies. However, the exploration of the reaction conditions (Table 1) indicated that these initial conditions performed better. In fact, the reaction failed in any solvent investigated other than toluene, while a reduction in the equivalents of triethylsilane or the catalyst load resulted in a decreased yield (Entries 3 and 4), with the reaction not proceeding to completion. The reaction also failed at room temperature or when no catalyst was present (Entries 6 and 5), and
a significant reduction in the percent conversion was observed when the temperature was reduced to 100 °C or when the reaction time was shortened to only 6 h, with the reaction not proceeding to completion in both cases. As a result, the initial conditions (Entry 1) were used for exploration of the reaction scope. A number of aliphatic and substituted aromatic oximes were O-silytated by heating them at reflux in toluene in the presence of triethylsilane (1.2 eq.) and H2PtCl66H2O (0.01 mol%) for 18 h, under a nitrogen atmosphere as summarized in Fig. 1. Most of
Fig. 1. H2PtCl66H2O catalyzed O-silylation of oximes using triethylsilane (isolated yields from 0.5 g reactions).
1638
S.V. Bhatt et al. / Tetrahedron Letters 60 (2019) 1636–1639
these reactions produced the expected product in good yields. Aliphatic, unsubstituted aromatic or aromatic rings possessing electron-donating groups gave the best yields. Furthermore, a chlorine substituent on the aromatic ring did not significantly affect the yield as illustrated by compounds 3, 13 and 16. However, the presence of a stronger electron-withdrawing group such as trifluoromethyl (4 and 14) resulted in low yields, while the reaction failed when the aromatic ring possessed a nitro group as a substituent. In most of the reactions using starting materials that were mixtures of oxime isomers, no significant change in the isomeric ratio was observed in the final products. The only exceptions were for compounds 15 and 17, which possess a substituent at an ortho position to the oxime functional group, for which the isomers ratio in the product was different from that of the starting material. In fact, the reaction of a mixture of (2,4-dimethoxyphenyl)(4-methoxyphenyl) methanone oxime (70:30 ratio) or a mixture of phenyl(o-tolyl)methanone oxime (67:33 ratio) with triethylsilane produced (2,4-dimethoxyphenyl)(4-methoxyphenyl)methanone O-triethylsilyl oxime (15, 81:19 ratio) and phenyl(o-tolyl)methanone O-triethylsilyl oxime (17, 80:20 ratio), respectively. This change is likely due to the increased steric hindrance that slowed down the rate of formation of one of the isomers in comparison to the rate of formation of the other one. In fact, in these cases, the reaction did not proceed to completion, and the unreacted starting materials were predominantly made of the slow reacting isomer. To investigate the reactivity of other silylating agents, triisopropylsilane, diethoxymethylsilane, triphenylsilane and triethoxysilane were tested, primarily with symmetrical and unhindered oximes. Triisopropylsilane and diethoxymethylsilane produced the expected product as illustrated in Fig. 2, although none of these reactions proceeded to completion under the above-described optimized conditions, and as a result, the isolated yields were significantly lower. It should however be noted that the reaction between a mixture of cyclohexyl(phenyl)methanone oxime (62:38 ratio) and diethoxymethylsilane produced almost exclusively one of the isomers of the expected product (25, 98:traces ratio) (cf. ESI), and the unreacted starting materials was predominantly made of the slow reacting isomer. Another surprising result was that the reaction systematically failed when triphenylsilane was used as the silylating agent. This latter observation is in contrast with previous reports on the preparation of O-silylated oximes using hydrosilanes in which triphenylsilane produced much better yields than trialkylsilanes, suggesting that
the rate of condensation increases with increasing electrophilicity on the silicon atom [14,17]. It is still unclear why triphenylsilane failed to react under the reaction conditions developed in this study, or why a dramatic change in isomeric ratio was observed for compound 25. Meanwhile, the reactions with triethoxysilane also produced the expected products, as indicated by GC–MS. However, attempts at the isolation of the resulting orthosilicates by silica gel chromatography were unsuccessful as the respective products consistently decomposed during the purification process. In 1965, Lukevics and Voronkov [20] reported the silylation of alcohols with triorganosilanes in the presence of H2PtCl6. However, their report did not provide many details about the reaction and its scope. Since H2PtCl6 is the catalyst used in the current study to silylate oximes, it seemed reasonable to investigate how alcohols and phenols behave under the optimal conditions described above. As such, when heated at reflux in toluene with either triethylsilane or triisopropylsilane, in the presence of H2PtCl66H2O (0.01 mol%), the reaction produced a complex mixture as indicated by GC–MS, and the expected product was not observed, even at 60 °C. However, at room temperature with triethylsilane, the reaction mixture was much cleaner, showing only unreacted starting materials and the expected product. Nevertheless, the yield was very low as illustrated in Fig. 3. It should be noted that the reaction with triethylsilane failed whenever a phenol derivative was used, regardless of the electronic features of the substituent(s). The reaction also failed whenever either triisopropylsilane or triphenylsilane was used as the silylating agent, even with aliphatic alcohols. The reaction however produced the expected product when triethoxysilane was used, although the reaction never progressed to completion, even after 48 h. Unfortunately, as for the oxime derivatives, the resulting orthosilicates decomposed during purification attempts by a silica gel chromatography, with 28 being the only compound that could be isolated and fully characterized.
Fig. 3. O-silylation of alcohols using trialkylsilane (isolated yields from 0.5 g reactions).
Fig. 2. O-silylation of oximes using other trialkylsilane (isolated yields from 0.5 g reactions).
S.V. Bhatt et al. / Tetrahedron Letters 60 (2019) 1636–1639
Conclusion An efficient method for the preparation of O-silylated aldoximes and ketoximes through a platinum-catalyzed silylation reaction using trisubstituted organosilanes has been developed. The reaction works well with triethylsilane, producing good yields for aromatic and aliphatic oximes, but only moderately with triisopropylsilane or diethoxymethylsilane. The reaction also appeared to work well with triethoxysilane although the resulting product could not be isolated. On the other hand, the reaction failed whenever triphenylsilane was used as a silylating agent. Finally, when alcohols or phenols were used as starting materials under similar conditions as the oximes, a complex mixture was obtained, and the expected product was not observed. However, at room temperature, the reaction with alcohols led to the expected product in low yields with triethylsilane or triethoxysilane, but failed whenever a phenol was used instead. Under these conditions, triisopropylsilane or triphenylsilane did not produce any product with either alcohols or phenols as starting materials. Going forward, the O-silylated aldoxime and ketoxime derivatives prepared during this study are currently being explored in our research group as potential starting materials in the asymmetric synthesis of amines. It is anticipated that even the orthosilicate derivatives of these oximes, prepared but not isolated during this study, could play an important role (in situ) in this new venture.
[2] [3]
[4] [5] [6] [7] [8]
[9] [10]
Acknowledgements J.F. acknowledges the financial support from the Louisiana Board of Regents’ Research and Development Program, Industrial Ties Research Subprogram (ITRS) LEQSF(2015-18)-RD-B-04.
[11]
Appendix A. Supplementary data Supplementary information associated with this article including the experimental data, 1H and 13C-NMR, and the GC-MS spectra featuring the isomeric ratios in each of the products reported. Supplementary data to this article can be found online at https://doi.org/10.1016/j.tetlet.2019.05.033. References [1] (a) P.I. Abronina, N.N. Malysheva, V.V. Litvinenko, A.I. Zinin, N.G. Kolotyrkina, L.O. Kononov, Org. Lett. 20 (2018) 6051–6054; (b) R.B. Othman, M.J. Fer, L.L. Corre, S. Calvet-Vitale, C. Gravier-Pelletier, Beilstein J. Org. Chem. 13 (2017) 1533–1541; (c) R. Mir, T. Dudding, J. Org. Chem. 82 (2017) 709–714; (d) J. Fassler, J.A. McCubbin, A. Roglans, T. Kimachi, J.W. Hollett, R.W. Kunz, M. Tinkl, Y. Zhang, R. Wang, M. Campbell, V. Snieckus, J. Org. Chem. 80 (2015) 3368–3386; (e) A. Phanumartwiwath, T.W. Hornsby, J. Jamalis, C.D. Bailey, C.L. Willis, Org.
[12] [13] [14] [15] [16] [17] [18]
[19] [20]
1639
Lett. 15 (2013) 5734–5737; (f) Y. Cui, Z. Cheng, J. Mao, Y. Yu, Tetrahedron Lett. 54 (2013) 3831–3833; (g) S.D. Stamatov, J. Stawinski, Org. Biomol. Chem. 8 (2010) 463–477; (h) D.L.J. Clive, J. Wang, Angew. Chem. Int. Ed. 42 (2003) 3406–3409; (i) S.A. Scaringe, F.E. Wincott, M.H. Caruthers, J. Am. Chem. Soc. 120 (1998) 11820–11821. M. Ortiz-Marciales, L. Pinero, L. Ufret, W. Algarin, J. Morales, Synth. Commun. 28 (1998) 2807–2811. (a) M. Ortiz-Marciales, E. Cruz, I. Alverio, D. Figueroa, J.F. Cordero, J. Morales, J. A. Soto, H. Dashmana, C. Burgos, J. Chem. Res. Synop. 1 (1998) 10–11; (b) M. Ortiz-Marciales, D. Figueroa, J.A. Lopez, M. De Jesus, R. Vega, Tetrahedron Lett. 41 (2000) 6567–6570; (c) M. Ortiz-Marciales, L.D. Rivera, M. De Jesus, S. Espinosa, J.A. Benjamin, O.E. Casanova, I.G. Figueroa, S. Rodriguez, W. Correa, J. Org. Chem. 70 (2005) 10132–10134; (d) M. Ortiz-Marciales, L.M. Tirado, R. Colon, M.L. Ufret, R. Figueroa, M. Lebron, M. DeJesus, J. Martinez, T. Malave, Synth Commun. 28 (1998) 4067–4075. (a) N.A. LeBel, N. Balasubramanian, Tetrahedron Lett. 26 (1985) 4331–4334; (b) J. Maciaszczyk, M. Jasinski, Tetrahedron: Asymmetry 26 (2015) 510–515. A. Heydari, M. Mehrdad, H. Tavakol, Synthesis 13 (2003) 1962–1964. M. Ortiz-Marciales, M. De Jesus, L. Quinones, D. Figueroa, Y.L. Montes, C. Burgos, B. Moctezuma, Tetrahedron 55 (1999) 12275–12286. X. Dong, Y. Kita, M. Oestreich, Angew. Chem. Int. Ed. 57 (2018) 10728–10731. (a) B. Molnar, B. Fodor, I. Boldizsar, I. Molnar-Perl, J. Chromatogr. A 1440 (2016) 172–178; (b) G. Aghapour, M.A. Kazemi, S. Nadali, J. Chin. Chem. Soc. 62 (2015) 197– 203; (c) H.R. Shaterian, R. Doostmohammadi, M. Ghashang, Chin. J. Chem. 26 (2008) 1709–1714; (d) H.R. Shaterian, M. Ghashang, N.T. Riki, M. Asadi, Can. J. Chem. 86 (2008) 841–845. E. Frainnet, F. Duboudin, C.R. Seances, Acad. Sci. Ser. C 262 (1966) 1693–1696. (a) C. Castro, M. Dixon, I. Erden, P. Ergonenc, J.R. Keeffe, A. Sukhovitsky, J. Org. Chem. 54 (1989) 3732–3738; (b) M.D. Fletcher, T.E. Hurst, T.J. Miles, C.J. Moody, Tetrahedron 62 (2006) 5454–5463; (c) A.A. Tabolin, A.V. Lesiv, Y.A. Khomutova, Y.V. Nelyubina, S.L. Ioffe, Tetrahedron 65 (2009) 4578–4592. (a) J. Mohr, M. Oestreich, Angew. Chem. Int. Ed. 53 (2014) 13278–13281; (b) S.R. Haadsma-Svensson, K.A. Cleek, D.M. Dinh, J.N. Duncan, C.L. Haber, R.M. Huff, M.E. Lajiness, N.F. Nichols, M.W. Smith, K.A. Svensson, M.J. Zaya, A. Carlsson, C.-H. Lin, J. Med. Chem. 44 (2001) 4716–4732; (c) M. Schlegel, C. Schneider, Chem. Commun. 54 (2018) 11124–11127; (d) P.S. Chauhan, S.M. Weinreb, J. Org. Chem. 79 (2014) 6389–6393; (e) Y. Feng, M.M. Majireck, S.M. Weinreb, Angew. Chem. Int. Ed. 51 (2012) 12846–12849; (f) M. Ortiz-Marciales, M. De Jesus, D. Figueroa, J. Hernandez, L. Vazquez, R. Vega, E.M. Morales, J.A. Lopez, Synth. Commun. 33 (2003) 311–323. M. Ortiz, J.F. Cordero, S. Pinto, I. Alverio, Synth Commun. 24 (1994) 409–415. J. Mohr, D. Porwal, I. Chatterjee, M. Oestreich, Chem. – Eur. J. 21 (2015) 17583– 17586. E. Lukevics, M. Dzintara, O.A. Pudova, Zh Obshch Khim. 53 (1983) 2054–2058. D. Gao, C. Cui, Chem. – Eur. J. 19 (2013) 11143–11147. M. Sridhar, J. Raveendra, B.C. Ramanaiah, C. Narsaiah, Tetrahedron Lett. 52 (2011) 5980–5982. E. Lukevics, R. Abele, M. Fleisher, J. Popelis, E. Abele, J. Mol. Catal. A: Chem. 198 (2003) 89–98. (a) J.L. Speier, J.A. Webster, G.H. Barnes, J. Am. Chem. Soc. 79 (1957) 974–979; (b) J.L. Speier, R. Zimmerman, J. Webster, J. Am. Chem. Soc. 78 (1956) 2278– 2281. B.J. Duke, E.N. Akeroyd, S.V. Bhatt, C.I. Onyeagusi, S.V. Bhatt, B.R. Adolph, J. Fotie, New J. Chem. 42 (2018) 11782–11795. E. Lukevics, M.G. Voronkov, Khim Geterotsikl Soedin. 2 (1965) 171–178.
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Pt-catalyzed O-silylation of oximes by tri-substituted organosilanes Shreeja V. Bhatt a, Shreya V. Bhatt a, Jean Fotie a,⇑ a
Department of Chemistry and Physics, Southeastern Louisiana University, SLU 10878, Hammond, LA 70402-0878, United States
a r t i c l e
i n f o
Article history: Received 30 March 2019 Revised 16 May 2019 Accepted 17 May 2019 Available online 23 May 2019 Keywords: O-silylation Speier’s catalyst Oximes Trisubstituted-hydrosilanes
a b s t r a c t Silylated derivatives of oximes are important intermediates in organic synthesis, and have found application in the preparation of various nitrogen containing compounds including nitriles, amines, nitrones, and hydroxylamines. An efficient method for the O-silylation of aldoximes and ketoximes through a platinum-catalyzed reaction using trisubstituted-hydrosilanes is described. The reaction works well with a range of aliphatic and aromatic oximes when using triethylsilane as a silylating agent. Furthermore, a number of tri-substituted organosilanes including triisopropylsilane, diethoxymethylsilane, triphenylsilane, and triethoxysilane were also explored. Ó 2019 Elsevier Ltd. All rights reserved.
Introduction O-silylation is a well-established strategy for functional group protection in multi-step organic syntheses, and has primarily been used for the protection of hydroxyl groups of alcohols, phenols, and carboxylic acids [1]. However, O-silylated aldoximes and ketoximes have progressively established themselves as important intermediates in the synthesis of nitriles [2], amines [3], nitrones [4], and hydroxylamines [5]. They have also found application in the synthesis of a-alkylsilylated oximes via O-silylated derivatives followed by the migration of the alkylsilyl group [6], as well as in the preparation of a-hydroxy-substituted oxime ethers by enantioselective Si–O coupling reactions [7]. As such, the preparation of O-silylated aldoximes and ketoximes has received a great deal of attention over the years. In general, O-silylated oximes are synthesized either by heating an oxime at reflux with hexamethyldisilazane (HMDS) [4a,8] or triethylsilanamine (Et3SiNH2) [9] in the presence of a catalyst, or by reacting it with trialkylchlorosilane in the presence of bases such as trimethylamine [10], imidazole [11] or NaH [12]. These latter silylating methods have been reported as sluggish, and often require an excess of chlorosilane and a stoichiometric amount of the base. [11a,c,d,13] There have also been a handful of reports on the preparation of silyl ethers of oximes using trialkylatedhydrosilanes in the presence of piperidine [14], 1,3-diisopropyl4,5-dimethylimidazol-2-ylidene [15], InBr3 [16] or fluorine [17]. With the above in mind, upon unexpectedly discovering that Speier’s catalyst (H2PtCl66H2O in isopropanol) could catalyze the ⇑ Corresponding author. E-mail address: [email protected] (J. Fotie). https://doi.org/10.1016/j.tetlet.2019.05.033 0040-4039/Ó 2019 Elsevier Ltd. All rights reserved.
O-silylation of 4-methylbenzaldehyde oxime in the presence of triethylsilane, it seemed appropriate to further explore the reaction as it could be of interest in organic synthesis.
Results and discussion Speier’s catalyst (H2PtCl66H2O in isopropanol) has been used for hydrosilylation reactions since the 1950s [18]. It was during a comparative analysis between Speier’s catalyst and Pt(0) nano-dispersed in a range of organically modified silicates as catalysts for hydrosilylation reactions [19], that we noted H2PtCl66H2O was able to catalyze the O-silylation of 4-methylbenzaldehyde oxime in the presence of triethylsilane, as illustrated in Scheme 1. An exploration of the reaction conditions was undertaken, and a number of solvents including toluene, acetonitrile, dichloromethane, 1,4-dioxane and THF were investigated. The catalyst loading was optimized, and the results are summarized in Table 1. As already mentioned, this reaction was discovered during a comparative analysis between Speier’s catalyst and Pt(0) nano-dispersed in a range of organically modified silicates as catalysts for
Scheme 1. O-silylation of 4-methylbenzaldehyde oxime in the presence of H2PtCl66H2O.
1637
S.V. Bhatt et al. / Tetrahedron Letters 60 (2019) 1636–1639 Table 1 Exploration of the reaction conditions using 4-methylbenzaldehyde oxime and triethylsilane. Entries
Et3SiH (eq.a)
H2PtCl66H2O (mol%)
Solvent
Temperature
Time (h)
Percent conversion (%)b
1 2 3 4 5 6 7 8 9 10 11 12
1.2 2 1 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2
0.01 0.01 0.01 0.005 None 0.01 0.01 0.01 0.01 0.01 0.01 0.01
Toluene Toluene Toluene Toluene Toluene Toluene Toluene Toluene CH3CN CH2Cl2 1,4-Dioxane THF
Reflux Reflux Reflux Reflux Reflux Rt 100 °C Reflux Reflux Reflux Reflux Reflux
18 18 18 18 18 18 18 6 18 18 18 18
95c 94c 82 62 NRd NRd 78 67 Trace NRd Trace NRd
Reactions were performed under a nitrogen atmosphere, using 100 mg of 4-methylbenzaldehyde oxime. a In relationship to the number of moles of 4-methylbenzaldehyde oxime. b Percent conversions determined by GC–MS, using tridecane as an internal standard. c No starting material was present upon reaction completion as indicated by the GC–MS spectrum. d N.R. = No Reaction.
the hydrosilylation reactions [19], and as such, the initial conditions (Entry 1) were carried over from these aforementioned studies. However, the exploration of the reaction conditions (Table 1) indicated that these initial conditions performed better. In fact, the reaction failed in any solvent investigated other than toluene, while a reduction in the equivalents of triethylsilane or the catalyst load resulted in a decreased yield (Entries 3 and 4), with the reaction not proceeding to completion. The reaction also failed at room temperature or when no catalyst was present (Entries 6 and 5), and
a significant reduction in the percent conversion was observed when the temperature was reduced to 100 °C or when the reaction time was shortened to only 6 h, with the reaction not proceeding to completion in both cases. As a result, the initial conditions (Entry 1) were used for exploration of the reaction scope. A number of aliphatic and substituted aromatic oximes were O-silytated by heating them at reflux in toluene in the presence of triethylsilane (1.2 eq.) and H2PtCl66H2O (0.01 mol%) for 18 h, under a nitrogen atmosphere as summarized in Fig. 1. Most of
Fig. 1. H2PtCl66H2O catalyzed O-silylation of oximes using triethylsilane (isolated yields from 0.5 g reactions).
1638
S.V. Bhatt et al. / Tetrahedron Letters 60 (2019) 1636–1639
these reactions produced the expected product in good yields. Aliphatic, unsubstituted aromatic or aromatic rings possessing electron-donating groups gave the best yields. Furthermore, a chlorine substituent on the aromatic ring did not significantly affect the yield as illustrated by compounds 3, 13 and 16. However, the presence of a stronger electron-withdrawing group such as trifluoromethyl (4 and 14) resulted in low yields, while the reaction failed when the aromatic ring possessed a nitro group as a substituent. In most of the reactions using starting materials that were mixtures of oxime isomers, no significant change in the isomeric ratio was observed in the final products. The only exceptions were for compounds 15 and 17, which possess a substituent at an ortho position to the oxime functional group, for which the isomers ratio in the product was different from that of the starting material. In fact, the reaction of a mixture of (2,4-dimethoxyphenyl)(4-methoxyphenyl) methanone oxime (70:30 ratio) or a mixture of phenyl(o-tolyl)methanone oxime (67:33 ratio) with triethylsilane produced (2,4-dimethoxyphenyl)(4-methoxyphenyl)methanone O-triethylsilyl oxime (15, 81:19 ratio) and phenyl(o-tolyl)methanone O-triethylsilyl oxime (17, 80:20 ratio), respectively. This change is likely due to the increased steric hindrance that slowed down the rate of formation of one of the isomers in comparison to the rate of formation of the other one. In fact, in these cases, the reaction did not proceed to completion, and the unreacted starting materials were predominantly made of the slow reacting isomer. To investigate the reactivity of other silylating agents, triisopropylsilane, diethoxymethylsilane, triphenylsilane and triethoxysilane were tested, primarily with symmetrical and unhindered oximes. Triisopropylsilane and diethoxymethylsilane produced the expected product as illustrated in Fig. 2, although none of these reactions proceeded to completion under the above-described optimized conditions, and as a result, the isolated yields were significantly lower. It should however be noted that the reaction between a mixture of cyclohexyl(phenyl)methanone oxime (62:38 ratio) and diethoxymethylsilane produced almost exclusively one of the isomers of the expected product (25, 98:traces ratio) (cf. ESI), and the unreacted starting materials was predominantly made of the slow reacting isomer. Another surprising result was that the reaction systematically failed when triphenylsilane was used as the silylating agent. This latter observation is in contrast with previous reports on the preparation of O-silylated oximes using hydrosilanes in which triphenylsilane produced much better yields than trialkylsilanes, suggesting that
the rate of condensation increases with increasing electrophilicity on the silicon atom [14,17]. It is still unclear why triphenylsilane failed to react under the reaction conditions developed in this study, or why a dramatic change in isomeric ratio was observed for compound 25. Meanwhile, the reactions with triethoxysilane also produced the expected products, as indicated by GC–MS. However, attempts at the isolation of the resulting orthosilicates by silica gel chromatography were unsuccessful as the respective products consistently decomposed during the purification process. In 1965, Lukevics and Voronkov [20] reported the silylation of alcohols with triorganosilanes in the presence of H2PtCl6. However, their report did not provide many details about the reaction and its scope. Since H2PtCl6 is the catalyst used in the current study to silylate oximes, it seemed reasonable to investigate how alcohols and phenols behave under the optimal conditions described above. As such, when heated at reflux in toluene with either triethylsilane or triisopropylsilane, in the presence of H2PtCl66H2O (0.01 mol%), the reaction produced a complex mixture as indicated by GC–MS, and the expected product was not observed, even at 60 °C. However, at room temperature with triethylsilane, the reaction mixture was much cleaner, showing only unreacted starting materials and the expected product. Nevertheless, the yield was very low as illustrated in Fig. 3. It should be noted that the reaction with triethylsilane failed whenever a phenol derivative was used, regardless of the electronic features of the substituent(s). The reaction also failed whenever either triisopropylsilane or triphenylsilane was used as the silylating agent, even with aliphatic alcohols. The reaction however produced the expected product when triethoxysilane was used, although the reaction never progressed to completion, even after 48 h. Unfortunately, as for the oxime derivatives, the resulting orthosilicates decomposed during purification attempts by a silica gel chromatography, with 28 being the only compound that could be isolated and fully characterized.
Fig. 3. O-silylation of alcohols using trialkylsilane (isolated yields from 0.5 g reactions).
Fig. 2. O-silylation of oximes using other trialkylsilane (isolated yields from 0.5 g reactions).
S.V. Bhatt et al. / Tetrahedron Letters 60 (2019) 1636–1639
Conclusion An efficient method for the preparation of O-silylated aldoximes and ketoximes through a platinum-catalyzed silylation reaction using trisubstituted organosilanes has been developed. The reaction works well with triethylsilane, producing good yields for aromatic and aliphatic oximes, but only moderately with triisopropylsilane or diethoxymethylsilane. The reaction also appeared to work well with triethoxysilane although the resulting product could not be isolated. On the other hand, the reaction failed whenever triphenylsilane was used as a silylating agent. Finally, when alcohols or phenols were used as starting materials under similar conditions as the oximes, a complex mixture was obtained, and the expected product was not observed. However, at room temperature, the reaction with alcohols led to the expected product in low yields with triethylsilane or triethoxysilane, but failed whenever a phenol was used instead. Under these conditions, triisopropylsilane or triphenylsilane did not produce any product with either alcohols or phenols as starting materials. Going forward, the O-silylated aldoxime and ketoxime derivatives prepared during this study are currently being explored in our research group as potential starting materials in the asymmetric synthesis of amines. It is anticipated that even the orthosilicate derivatives of these oximes, prepared but not isolated during this study, could play an important role (in situ) in this new venture.
[2] [3]
[4] [5] [6] [7] [8]
[9] [10]
Acknowledgements J.F. acknowledges the financial support from the Louisiana Board of Regents’ Research and Development Program, Industrial Ties Research Subprogram (ITRS) LEQSF(2015-18)-RD-B-04.
[11]
Appendix A. Supplementary data Supplementary information associated with this article including the experimental data, 1H and 13C-NMR, and the GC-MS spectra featuring the isomeric ratios in each of the products reported. Supplementary data to this article can be found online at https://doi.org/10.1016/j.tetlet.2019.05.033. References [1] (a) P.I. Abronina, N.N. Malysheva, V.V. Litvinenko, A.I. Zinin, N.G. Kolotyrkina, L.O. Kononov, Org. Lett. 20 (2018) 6051–6054; (b) R.B. Othman, M.J. Fer, L.L. Corre, S. Calvet-Vitale, C. Gravier-Pelletier, Beilstein J. Org. Chem. 13 (2017) 1533–1541; (c) R. Mir, T. Dudding, J. Org. Chem. 82 (2017) 709–714; (d) J. Fassler, J.A. McCubbin, A. Roglans, T. Kimachi, J.W. Hollett, R.W. Kunz, M. Tinkl, Y. Zhang, R. Wang, M. Campbell, V. Snieckus, J. Org. Chem. 80 (2015) 3368–3386; (e) A. Phanumartwiwath, T.W. Hornsby, J. Jamalis, C.D. Bailey, C.L. Willis, Org.
[12] [13] [14] [15] [16] [17] [18]
[19] [20]
1639
Lett. 15 (2013) 5734–5737; (f) Y. Cui, Z. Cheng, J. Mao, Y. Yu, Tetrahedron Lett. 54 (2013) 3831–3833; (g) S.D. Stamatov, J. Stawinski, Org. Biomol. Chem. 8 (2010) 463–477; (h) D.L.J. Clive, J. Wang, Angew. Chem. Int. Ed. 42 (2003) 3406–3409; (i) S.A. Scaringe, F.E. Wincott, M.H. Caruthers, J. Am. Chem. Soc. 120 (1998) 11820–11821. M. Ortiz-Marciales, L. Pinero, L. Ufret, W. Algarin, J. Morales, Synth. Commun. 28 (1998) 2807–2811. (a) M. Ortiz-Marciales, E. Cruz, I. Alverio, D. Figueroa, J.F. Cordero, J. Morales, J. A. Soto, H. Dashmana, C. Burgos, J. Chem. Res. Synop. 1 (1998) 10–11; (b) M. Ortiz-Marciales, D. Figueroa, J.A. Lopez, M. De Jesus, R. Vega, Tetrahedron Lett. 41 (2000) 6567–6570; (c) M. Ortiz-Marciales, L.D. Rivera, M. De Jesus, S. Espinosa, J.A. Benjamin, O.E. Casanova, I.G. Figueroa, S. Rodriguez, W. Correa, J. Org. Chem. 70 (2005) 10132–10134; (d) M. Ortiz-Marciales, L.M. Tirado, R. Colon, M.L. Ufret, R. Figueroa, M. Lebron, M. DeJesus, J. Martinez, T. Malave, Synth Commun. 28 (1998) 4067–4075. (a) N.A. LeBel, N. Balasubramanian, Tetrahedron Lett. 26 (1985) 4331–4334; (b) J. Maciaszczyk, M. Jasinski, Tetrahedron: Asymmetry 26 (2015) 510–515. A. Heydari, M. Mehrdad, H. Tavakol, Synthesis 13 (2003) 1962–1964. M. Ortiz-Marciales, M. De Jesus, L. Quinones, D. Figueroa, Y.L. Montes, C. Burgos, B. Moctezuma, Tetrahedron 55 (1999) 12275–12286. X. Dong, Y. Kita, M. Oestreich, Angew. Chem. Int. Ed. 57 (2018) 10728–10731. (a) B. Molnar, B. Fodor, I. Boldizsar, I. Molnar-Perl, J. Chromatogr. A 1440 (2016) 172–178; (b) G. Aghapour, M.A. Kazemi, S. Nadali, J. Chin. Chem. Soc. 62 (2015) 197– 203; (c) H.R. Shaterian, R. Doostmohammadi, M. Ghashang, Chin. J. Chem. 26 (2008) 1709–1714; (d) H.R. Shaterian, M. Ghashang, N.T. Riki, M. Asadi, Can. J. Chem. 86 (2008) 841–845. E. Frainnet, F. Duboudin, C.R. Seances, Acad. Sci. Ser. C 262 (1966) 1693–1696. (a) C. Castro, M. Dixon, I. Erden, P. Ergonenc, J.R. Keeffe, A. Sukhovitsky, J. Org. Chem. 54 (1989) 3732–3738; (b) M.D. Fletcher, T.E. Hurst, T.J. Miles, C.J. Moody, Tetrahedron 62 (2006) 5454–5463; (c) A.A. Tabolin, A.V. Lesiv, Y.A. Khomutova, Y.V. Nelyubina, S.L. Ioffe, Tetrahedron 65 (2009) 4578–4592. (a) J. Mohr, M. Oestreich, Angew. Chem. Int. Ed. 53 (2014) 13278–13281; (b) S.R. Haadsma-Svensson, K.A. Cleek, D.M. Dinh, J.N. Duncan, C.L. Haber, R.M. Huff, M.E. Lajiness, N.F. Nichols, M.W. Smith, K.A. Svensson, M.J. Zaya, A. Carlsson, C.-H. Lin, J. Med. Chem. 44 (2001) 4716–4732; (c) M. Schlegel, C. Schneider, Chem. Commun. 54 (2018) 11124–11127; (d) P.S. Chauhan, S.M. Weinreb, J. Org. Chem. 79 (2014) 6389–6393; (e) Y. Feng, M.M. Majireck, S.M. Weinreb, Angew. Chem. Int. Ed. 51 (2012) 12846–12849; (f) M. Ortiz-Marciales, M. De Jesus, D. Figueroa, J. Hernandez, L. Vazquez, R. Vega, E.M. Morales, J.A. Lopez, Synth. Commun. 33 (2003) 311–323. M. Ortiz, J.F. Cordero, S. Pinto, I. Alverio, Synth Commun. 24 (1994) 409–415. J. Mohr, D. Porwal, I. Chatterjee, M. Oestreich, Chem. – Eur. J. 21 (2015) 17583– 17586. E. Lukevics, M. Dzintara, O.A. Pudova, Zh Obshch Khim. 53 (1983) 2054–2058. D. Gao, C. Cui, Chem. – Eur. J. 19 (2013) 11143–11147. M. Sridhar, J. Raveendra, B.C. Ramanaiah, C. Narsaiah, Tetrahedron Lett. 52 (2011) 5980–5982. E. Lukevics, R. Abele, M. Fleisher, J. Popelis, E. Abele, J. Mol. Catal. A: Chem. 198 (2003) 89–98. (a) J.L. Speier, J.A. Webster, G.H. Barnes, J. Am. Chem. Soc. 79 (1957) 974–979; (b) J.L. Speier, R. Zimmerman, J. Webster, J. Am. Chem. Soc. 78 (1956) 2278– 2281. B.J. Duke, E.N. Akeroyd, S.V. Bhatt, C.I. Onyeagusi, S.V. Bhatt, B.R. Adolph, J. Fotie, New J. Chem. 42 (2018) 11782–11795. E. Lukevics, M.G. Voronkov, Khim Geterotsikl Soedin. 2 (1965) 171–178.