A facile one-pot conversion of non-enolizable aldehydes to diazirines

Article abstract of DOI:10.1016/S0040-4039(99)02213-3

A general route to monoalkyl diazirines from non-enolizable aldehydes through N-trimethylsilyl diaziridines is described. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(99)02213-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 795–796
A facile one-pot conversion of non-enolizable aldehydes to
diazirines
∗
Igor R. Likhotvorik, Eunju Lee Tae, Celine Ventre and Matthew S. Platz
Department of Chemistry, The Ohio State University, Columbus, Ohio 43210, USA
Received 14 October 1999; revised 16 November 1999; accepted 17 November 1999
Abstract
A general route to monoalkyl diazirines from non-enolizable aldehydes through N-trimethylsilyl diaziridines is
described. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: carbene sources; diazirines; aldehydes; N-trimethylsilyl imines.
Diazirines are valuable precursors of carbenes. A variety of preparations have been reported for the
1
syntheses of dialkyl diazirines from ketones, but fewer options are available for mono alkyl diazirines
2
derived from aldehydes. This is particularly true in the case of aryl aldehydes. One of the reasons for this
difficulty is the instability of the intermediate diaziridines. To overcome this problem the most widely
2
a
used general synthetic preparation, discovered by Schmitz in the early sixties, requires a large excess
3
of the aldehyde to prepare a diaziridine triazolidine intermediate. Knowles discovered that these species
hydrolyze rapidly when R=aryl resulting in poor yields of 3-aryl-3-H diazirines.
Herein, we report a new approach to diazirines whereby stabilization of the intermediate diaziridine is
achieved by substitution of one of the reactive hydrogens with a trimethylsilyl group (Scheme 1).
2 3
Scheme 1. (i) LiHMDS, THF, ice bath; (ii) NH OSO H; (iii) t-BuOCl
We found that if aldehydes 1 are converted first to the N-(trimethylsilyl) imines 2 by reaction with
4
lithium bis(trimethylsilyl)amide, then addition of the hydroxylamine-O-sulfonic acid in the presence
of base affords the corresponding N-trimethylsilyl diaziridines 3 which are sufficiently stable, for our
∗
Corresponding author: Tel: (614) 457-7513; fax (614) 292-1685; e-mail: platz.1@osu.edu (M. S. Platz)
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040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02213-3
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purposes, to the reaction conditions. Transformation of these intermediates to alkyldiazirines 4 was
achieved by oxidation with tert-butylhypochlorite or N-chlorosuccinimide.
This three-step, one-pot synthesis, is best performed on non-enolizable substrates. Relatively good
yields with tertiary alkyl aldehydes were realized when the reaction was carried out at 0°C. In the
case of benzaldehyde 1d we found that the corresponding N-trimethylsilyldiaziridine 3d was less stable
than its alkyl counterparts and required cooling to about –30°C. We observed partial decomposition of
phenyldiazirine 4d during purification on a silica gel column. However, the 12% yield of the pure product
2
b
realized in this case was comparable with the best previously reported two-step procedures (13%).
The following experimental procedure is typical: To a stirred solution of 3-noradamantanecarbaldehyde5
1a (0.150 g, 1 mmol) in dry THF under argon (1.5 mL) cooled in an ice bath, 1 M lithium
bis(trimethylsilyl) amide solution in THF (2 mL) was added dropwise via syringe. After the addition was
complete the mixture was stirred for 0.5 h at 0°C, cooled to −30°C and a solution of hydroxylamine-
O-sulfonic acid (0.126 g, 1 mmol) in dry diglyme (1 mL) was added dropwise. The mixture was
6
stirred at 0°C for 1 h, then a solution of freshly prepared tert-butylhypochlorite (0.11 mL, 1 mmol) in
tert-butanol (0.12 mL) was added dropwise. (CAUTION! When tert-butylhypochlorite was added in
one portion explosive decomposition of a 10 mmol scale reaction mixture occurred!) The mixture was
7
8
stirred for another 1 h in the ice bath, poured into water (15 mL), extracted with pentane, washed
with water, dried over sodium sulfate, concentrated with a rotory evaporator at room temperature and
purified by column chromatography on silica gel with pentane. Evaporation of the solvent afforded
(
3-noradamantyl)diazirine 4a (0.11 g, 67%).9
Acknowledgements
We thank the National Science Foundation for generous support of this work through Grant CHE-
9613861.
References
1
2
. (a) For a review, see: Schmitz, E. In Chemistry of Diazirines; CRC Press: Boca Raton, 1987. (b) Paulsen, S. R. Angew. Chem.
960, 72, 781. (c) Kirmse, W.; Meinert, T.; Modarelli, D. A.; Platz, M. S. J. Am. Chem. Soc. 1993, 115, 8918.
. (a) Schmitz, E. Chem. Ber. 1962, 95, 688. (b) Smith, R. A. G.; Knowles, R. J. Chem. Soc., Perkin Trans. 2 1975, 686. (c)
Frey, H. M.; Stevens, I. D. R. J. Chem. Soc. 1965, 3101.
1
3
4
5
. Nielsen, A. T.; Moore, D. W.; Atkins, R. L.; Mallory, D.; DiPol, J. D.; LaBerge, J. M. J. Org. Chem. 1976, 41, 3221.
. Hart, D. J.; Kanai, K.; Thomas, D. G.; Yang, T.-K. J. Org. Chem. 1983, 48, 289.
. This aldehyde was prepared in 96% yield by Swern oxidation of 3-noradamantylmethanol: Mancuso, A. J.; Huang, S.-L.;
Swern, D. J. Org. Chem. 1978, 43, 2480.
6
7
. Mintz, M. J .; Walling, C. Organic Syntheses Coll. Vol. 5, 184.
. In the case of benzaldehyde 1d hydroxylamine-O-sulfonic acid was added to the mixture at −50°C, the mixture was stirred
at −30°C for 2 h, then tert-butylhypochlorite was added dropwise, the mixture was allowed to reach 0°C and stirred for 0.5
h.
8
. For the reaction with pivalaldehyde 1c (7 mmol) N-chlorosuccinimide (8 mmol, 18 h at 0–5°C) was used as the oxidant
instead of tert-butylhypochlorite. The mixture was extracted with decane, washed with water, and dried over sodium sulfate. A
slow stream of dry argon was bubbled through the decane solution, and the gas was passed through a 0°C trap to remove most
2
c
of the solvent and hexamethyldisiloxane. Volatiles were collected in a −78°C trap. Final purification of tert-butyldiazirine
4
c was achieved by preparative GC. Yield 41%.
1
9. Diazirines 4a,b are colorless liquids: Compound 4a, yield 67%. H NMR (CDCl ) δ 0.96 (s, 1H), 1.41–1.65 (m, 10H), 2.17
3
(
m, 2H), 2.24 (m, 1H); 13C NMR (CDCl
3
) δ 26.8, 34.9, 37.0, 41.3, 43.8, 46.0, 47.9, IR 1582 cm . UV (pentane) λmax 340
−1
+
1
nm. HRMS: 134.1090 (M −N
2
); calcd: 134.1096 for C10
H
14. Compound 4b, yield 45%. H NMR (CDCl
3
) δ 0.41 (s, 1H),
) δ 28.32, 29.79, 31.80, 36.94, 39.64. IR 1588
cm . UV (pentane) λmax 340, 352 nm. HRMS: 176.1304 (M ); calcd: 176.1317 for C11 ; Compound 4d, yield 12%.
1
3
1
.29 (m, 6H), 1.51 (m, 3H), 1.60 (m, 3H), 1.86 (m, 3H); C NMR (CDCl
3
−
1
+
16 2
H N