[22737-33-3]  · C7H21NOSi2  · N-Methyl-N,O-bis(trimethylsilyl)hydroxylamine  · (MW 191.47)

(bis-trimethylsilylated N-methylhydroxylamine;1-3 can convert aldehydes and ketones to N-methyl nitrones with regio- and chemoselectivity;3 source of methylnitrene by pyrolysis;4,5 source of the trimethylsilyl(methyl)aminyl radical by photolysis6)

Physical Data: bp 40-41 °C/10 mmHg;2,7,8 n20D 1.4146.2

Solubility: sol benzene, toluene, CH2Cl2, CHCl3.2

Form Supplied in: colorless liquid;2,8,9 commercially available.

Preparative Method: obtained in 52% yield by reaction of N-Methylhydroxylamine with Chlorotrimethylsilane (2.0 equiv) and Triethylamine (3.3 equiv) in ether at 25 °C.1,2

Handling, Storage, and Precautions: hydrolyzes readily upon exposure to moisture; stored without decomposition for several months in a sealed bottle at -10 to -15 °C;2 relatively thermally stable, having t1/2 of 46.5 h at 140 °C;4 dec at 180-190 °C.10

N-Methyl Nitrone Formation.

Aldehydes or ketones react with a stoichiometric amount of Me3SiN(Me)OSiMe3 (1) in benzene at 50 °C for 24 h to give N-methyl nitrones in good to excellent yields (eq 1).1 For deactivated carbonyl compounds, such as p-nitrobenzaldehyde, p-(dimethylamino)benzaldehyde, and 2-furaldehyde, addition of Trimethylsilyl Trifluoromethanesulfonate (0.03-0.04 equiv) as a catalyst is necessary for the formation of N-methyl nitrones; otherwise accumulation of hemiaminal intermediates (2) occurs. Sequential intra- and intermolecular [3 + 2] cycloadditions can be carried out in situ for substrates containing a C=C or a C=N double bond (eqs 2 and 3).

Regio- and Chemoselective Nitrone Formation.

The trimethylsilyl cationic (Me3Si+) moiety in Me3SiN(Me)OSiMe3 serves as a bulky proton,11 which enables this reagent to react selectively with carbonyl groups having different steric environments. For example, regioselective nitrone formation occurs exclusively at the C-3, instead of the sterically more crowded C-20, carbonyl group in 5a-pregnane-3,20-dione in benzene at reflux (eq 4). Also, Me3SiN(Me)OSiMe3 preferentially reacts with trimethylacetaldehyde in the presence of acetone to afford the corresponding nitrone. The selectivity offered by Me3SiN(Me)OSiMe3 is higher than that offered by MeNHOH.HCl (14:1 versus 6:1). Me3SiN(Me)OSiMe3 reacts preferentially with aldehyde functionality in the presence of chlorides. This is evidenced by the reaction of Me3SiN(Me)OSiMe3 with 5-chloropentanal (1.0 equiv) in CH2Cl2 at reflux to give a nitrone in 79% yield without any substitution product being formed.

Protection of the Carbonyl Group.

For carbonyl compounds containing a second reducible functionality, selective reduction of the latter can be accomplished by protection of the carbonyl group in its hemiaminal form by use of Me3SiN(Me)OSiMe3. An example is shown in eq 5, in which 4-cyanobenzaldehyde is first treated with 1.3 equiv of Me3SiN(Me)OSiMe3 to give a hemiaminal intermediate. In situ, 1.2 equiv of a reducing agent are added to afford terephthalaldehyde in 80-93% yields after acidic workup. The applicable reducing agents include NaBH4, Super-Hydride, L-Selectride, K-Selectride, LS-Selectride, BH3.THF, 9-BBN, DIBAL, Red-Al, and Bu3SnH.2 This method provides a way to carry out protection-reduction-deprotection in one flask.

Methylnitrene Formation.

Pyrolysis of Me3SiN(Me)OSiMe3 at 150 °C gives methylnitrene (Me&NNuml;:) through a-deoxysilylation.4,5 The nitrene intermediate can be trapped by (MeO)2MeSiH to give the insertion product (MeO)2MeSiNHMe.

Silylalkylaminyl Radical Formation.

Irradiation of Me3SiN(Me)OSiMe3 with 260-340 nm UV light gives the trimethylsilyl(methyl)aminyl radical (Me(Me3Si)N&bdot;).6 This radical is more reactive than the Me2N&bdot; radical and can be trapped by use of trialkyl phosphites to afford phosphoranyl radicals, such as &bdot;P(OEt)3N(Me)SiMe3.

1. Robl, J. A.; Hwu, J. R. JOC 1985, 50, 5913.
2. Hwu, J. R.; Robl, J. A.; Wang, N.; Anderson, D. A.; Ku, J.; Chen, E. JCS(P1) 1989, 1823.
3. Hwu, J. R.; Khoudary, K. P.; Tsay, S.-C. JOM 1990, 399, C13.
4. Chang, Y. H.; Chiu, F.-T.; Zon, G. JOC 1981, 46, 342.
5. Tsui, F. P.; Vogel, T. M.; Zon, G. JACS 1974, 96, 7144.
6. Brand, J. C.; Roberts, B. P.; Winter, J. N. JCS(P2) 1983, 261.
7. Smrekar, O.; Wannagat, U. M 1969, 100, 760.
8. West, R.; Boudjouk, P. JACS 1973, 95, 3987.
9. West, R.; Boudjouk, P.; Matuszko, A. JACS 1969, 91, 5184.
10. West, R.; Nowakowski, P.; Boudjouk, P. JACS 1976, 98, 5620.
11. Hwu, J. R.; Wetzel, J. M. JOC 1985, 50, 3946.

Jih Ru Hwu & Shwu-Chen Tsay

National Tsing Hua University, Taiwan, Republic of China

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