Pt-catalyzed O-silylation of oximes by tri-substituted organosilanes

Article abstract of DOI:10.1016/j.tetlet.2019.05.033

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

Full text of DOI:10.1016/j.tetlet.2019.05.033

Accepted Manuscript
Pt-catalyzed O-silylation of oximes by tri-substituted organosilanes
Shreeja V. Bhatt, Shreya V. Bhatt, Jean Fotie
PII:
S0040-4039(19)30475-7
https://doi.org/10.1016/j.tetlet.2019.05.033
TETL 50805
DOI:
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
30 March 2019
16 May 2019
17 May 2019
Please cite this article as: Bhatt, S.V., Bhatt, S.V., Fotie, J., Pt-catalyzed O-silylation of oximes by tri-substituted
organosilanes, Tetrahedron Letters (2019), doi: https://doi.org/10.1016/j.tetlet.2019.05.033
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Pt-catalyzed O-silylation of oximes by tri-substituted organosilanes
Shreeja V. Bhatt,a Shreya V. Bhatta and Jean Fotiea*
aDepartment of Chemistry and Physics, Southeastern Louisiana University, SLU 10878, Hammond, LA
70402-0878, United States
Abstract
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.
Key words: O-silylation, Speier’s catalyst, Oximes, Trisubstituted-hydrosilanes.
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 α-alkylsilylated oximes via O-silylated derivatives followed by
the migration of the alkylsilyl group,6 as well as in the preparation of α-hydroxy-substituted oxime ethers
by enantioselective Si–O coupling reactions.7
1
_______________
*Corresponding author. Tel.: (+1) 985-549-5112, Fax: (+1) 985-549-5126
E-mail address: jean.fotie@southeastern.edu (Jean Fotie)

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 imidazole11 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, 11c, 11d, 13 There have also been a handful of
reports on the preparation of silyl ethers of oximes using trialkylated-hydrosilanes in the presence of
piperidine,14 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene,15 InBr316 or fluorine.17
With the above in mind, upon unexpectedly discovering that Speier’s catalyst (H2PtCl6·6H2O in
isopropanol) could catalyze the 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 (H2PtCl6·6H2O 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
H2PtCl6·6H2O 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.
2

Scheme 1: O-silylation of 4-methylbenzaldehyde oxime in the presence of H2PtCl6·6H2O.
Table 1: Exploration of the reaction conditions using 4-methylbenzaldehyde oxime and triethylsilane
Entries Et3SiH (eq.a) H2PtCl6·6H2O
(mol%)
Solvent
Temperature
Time
(h)
Percent
conversion (%)b
1
2
1.2
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
reflux
reflux
reflux
reflux
reflux
rt
100 oC
reflux
reflux
reflux
reflux
reflux
18
18
18
18
18
18
18
6
95c
94c
3
1
82
4
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
62
NRd
NRd
78
5
6
7
8
67
9
18
18
18
18
trace
NRd
trace
NRd
10
11
12
CH2Cl2
1,4-Dioxane
THF
a
Reactions were performed under a nitrogen atmosphere, using 100 mg of 4-methylbenzaldehyde oxime. In relationship to the number of
b
c
moles of 4-methylbenzaldehyde oxime. Percent conversions determined by GC-MS, using tridecane as an internal standard. No starting
material was present upon reaction completion as indicated by the GC-MS spectrum. dN.R. = No Reaction.
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 the
hydrosilylation reactions,19 and as such, the initial conditions (Entry 1) were carried over from these
3

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
o
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 H2PtCl6·6H2O (0.01 mol%) for 18 h, under a
nitrogen atmosphere as summarized in Figure 1. Most of 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 isomer, 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
4

did not proceed to completion, and the unreacted starting materials were predominantly made of the
slow reacting isomer.
Figure 1: H2PtCl6·6H2O catalyzed O-silylation of oximes using triethylsilane (isolated yields from 0.5 g
reactions).
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 Figure 2,
5

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
Figure 2: O-silylation of oximes using other trialkylsilane (isolated yields from 0.5 g reactions).
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
6

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 Voronkov20 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
H2PtCl6·6H2O (0.01 mol%), the reaction produced a complex mixture as indicated by GC-MS, and the
o
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 Figure 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 hours. 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.
7

Figure 3: O-silylation of alcohols using trialkylsilane (isolated yields from 0.5 g reactions).
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.
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.
8

Supplementary data
1
Supplementary information associated with this article including the experimental data, H and 13C-
NMR, and the GC-MS spectra featuring the isomeric ratios in each of the products reported can be
found in the online version, at
References
1. (a) Abronina PI, Malysheva NN, Litvinenko VV, Zinin AI, Kolotyrkina NG, Kononov LO. Org Lett.
2018;20:6051-6054; (b) Othman RB, Fer MJ, Corre LL, Calvet-Vitale S, Gravier-Pelletier C. Beilstein J
Org Chem. 2017;13:1533-1541; (c) Mir R, Dudding T. J Org Chem. 2017;82:709-714; (d) Fassler J,
McCubbin JA, Roglans A, Kimachi T, Hollett JW, Kunz RW, Tinkl M, Zhang Y, Wang R, Campbell M,
Snieckus V. J Org Chem. 2015;80:3368-3386; (e) Phanumartwiwath A, Hornsby TW, Jamalis J,
Bailey CD, Willis CL. Org Lett. 2013;15:5734-5737; (f) Cui Y, Cheng Z, Mao J, Yu Y. Tetrahedron Lett.
2013;54:3831-3833; (g) Stamatov SD, Stawinski J. Org Biomol Chem. 2010; 8:463-477; (h) Clive DLJ,
Wang J. Angew Chem, Int Ed. 2003;42:3406-3409; (i) Scaringe SA, Wincott FE, Caruthers MH. J Am
Chem Soc. 1998;120:11820-11821.
2. Ortiz-Marciales M, Pinero L, Ufret L, Algarin W, Morales J. Synth Commun. 1998;28:2807-2811.
3. Ortiz-Marciales M, Cruz E, Alverio I, Figueroa D, Cordero JF, Morales J, Soto JA, Dashmana H,
Burgos C. J Chem Res, Synop. 1998;(1):10-11; (b) Ortiz-Marciales M, Figueroa D, Lopez JA, De Jesus
M, Vega R. Tetrahedron Lett. 2000;41:6567-6570; (c) Ortiz-Marciales M, Rivera LD, De Jesus M,
Espinosa S, Benjamin JA, Casanova OE, Figueroa IG, Rodriguez S, Correa W. J Org Chem.
9
_______________
*Corresponding author. Tel.: (+1) 985-549-5112, Fax: (+1) 985-549-5126
E-mail address: jean.fotie@southeastern.edu (Jean Fotie)

2005;70:10132-10134; (d) Ortiz-Marciales M, Tirado LM, Colon R, Ufret ML, Figueroa R, Lebron M,
DeJesus M, Martinez J, Malave T. Synth Commun. 1998;28:4067-4075.
4. (a) LeBel NA, Balasubramanian N. Tetrahedron Lett. 1985;26:4331-4; (b) Maciaszczyk J, Jasinski M.
Tetrahedron: Asymmetry 2015;26:510-515.
5. Heydari A, Mehrdad M, Tavakol H. Synthesis 2003;(13):1962-1964.
6. Ortiz-Marciales M, De Jesus M, Quinones L, Figueroa D, Montes YL, Burgos C, Moctezuma B.
Tetrahedron 1999;55:12275-12286.
7. Dong X, Kita Y, Oestreich M. Angew Chem, Int Ed. 2018;57:10728-10731.
8. Molnar B, Fodor B, Boldizsar I, Molnar-Perl I. J Chromatogr. A 2016;1440:172-178; (b) Aghapour G,
Kazemi MA, Nadali S. J Chin Chem Soc. 2015;62:197-203; (c) Shaterian HR, Doostmohammadi R,
Ghashang M. Chin J Chem. 2008;26:1709-1714; (d) Shaterian HR, Ghashang M, Riki NT, Asadi M.
Can J Chem. 2008;86:841-845.
9. Frainnet E, Duboudin F. C R Seances Acad Sci, Ser. C 1966;262:1693-1696.
10. Castro C, Dixon M, Erden I, Ergonenc P, Keeffe JR, Sukhovitsky A. J Org Chem. 1989;54:3732-3738;
(b) Fletcher MD, Hurst TE, Miles TJ, Moody CJ. Tetrahedron 2006;62:5454-5463; (c) Tabolin AA,
Lesiv AV, Khomutova YA, Nelyubina YV, Ioffe SL. Tetrahedron 2009;65:4578-4592.
11. (a) Mohr J, Oestreich M. Angew Chem, Int Ed. 2014;53:13278-13281; (b) Haadsma-Svensson SR.,
Cleek KA, Dinh DM, Duncan JN, Haber CL, Huff RM, Lajiness ME, Nichols NF, Smith MW, Svensson
KA, Zaya MJ, Carlsson A, Lin C-H. J Med Chem. 2001;44:4716-4732; (c) Schlegel M, Schneider C.
Chem Commun. 2018;54:11124-11127; (d) Chauhan PS, Weinreb SM. J Org Chem. 2014;79:6389-
6393; (e) Feng Y, Majireck MM, Weinreb SM. Angew Chem, Int Ed. 2012;51:12846-12849; (f) Ortiz-
10

Marciales M, De Jesus M, Figueroa D, Hernandez J, Vazquez L, Vega R, Morales EM, Lopez JA.
Synth Commun. 2003;33:311-323.
12. Ortiz M, Cordero JF, Pinto S, Alverio I. Synth Commun. 1994;24:409-415.
13. Mohr J, Porwal D, Chatterjee I, Oestreich M. Chem - Eur J. 2015;21:17583-17586.
14. Lukevics E, Dzintara M, Pudova OA. Zh Obshch Khim. 1983;53:2054-2058.
15. Gao D, Cui C. Chem - Eur J. 2013;19:11143-11147.
16. Sridhar M, Raveendra J, Ramanaiah BC, Narsaiah C. Tetrahedron Lett. 2011;52:5980-5982.
17. Lukevics E, Abele R, Fleisher, M, Popelis J, Abele E. J Mol Catal A: Chem. 2003;198:89-98.
18. (a) Speier JL, Webster JA, Barnes GH. J Am Chem Soc. 1957;79:974-979; (b) Speier JL, Zimmerman
R, Webster J. J Am Chem Soc. 1956;78:2278-81.
19. Duke BJ, Akeroyd EN, Bhatt SV, Onyeagusi CI, Bhatt SV, Adolph BR, Fotie, J. New J Chem.
2018;42:11782-11795.
20. Lukevics E, Voronkov MG. Khim Geterotsikl Soedin. 1965;(2):171-178.
11

Highlights

Aldoximes and ketoximes are O-silylated by trisubstituted-hydrosilanes in the presence of
Speier’s catalyst



Strong electron withdrawing groups on aromatic oximes are detrimental to the reaction
The reaction works well with triethylsilane and moderately with other organosilanes
These reaction conditions are not suitable for alcohols and phenols.
12

Graphical Abstract
Pt-catalyzed O-silylation of oximes by tri-substituted organosilanes
Leave this area blank for abstract
Shreeja V. Bhatt,a Shreya V. Bhatta and Jean Fotie,a*
13