Nonstabilised Azomethine Ylids from N-Oxides
1315
exotherm was observed. When no further heat was generated
(30 min) the reaction was cooled to 08C and a further portion of
ethylbromide (0.20 mL, 0.25 equiv.) was added and the ice bath
was removed. After stirring at r.t. for a period of a 100 min gentle
vacuum was applied to remove volatiles and the crude was
washed with acetone. After applying gentle vacuum to remove
the remaining acetone, excess solid pellets of NaOH was added
and the mixture was stirred for a period of 30 min. The crude
residue was placed under high vacuum (,0.1 Torr) and the
product was captured using a liquid nitrogen trap. When most of
the product was captured, the crude was slowly heated to 608C
for a brief period to afford the tertiary amine 13 (527 mg, 48 %)
as a colourless liquid. dH (300 MHz, CDCl3) 3.58 (dd, J 5.5, 2H),
2.55–2.44 (m, 4H), 2.24 (s, 3H), 1.06 (t, J 7.1, 3H). This material
is commercially available.
10 min (effervescence was observed over the course of few min
and the reaction became homogeneous and yellow in colour).
The reaction was allowed to slowly reach r.t. and was subse-
quently quenched (saturated aqueous solution of NH4Cl) 3 h
after addition of MDA. The aqueous phase was extracted using
EtOAc, and the combined organic phase was washed with brine
and dried over MgSO4. The crude mixture was purified by silica
column chromatography (EtOAc) to afford 6 (109 mg, 18 %) as
a colourless oil. dH (500 MHz, CDCl3) 7.31–7.14 (m, 10H), 4.29
(dd, J 12.8, 3.7, 1H), 4.11 (dq, J 9.6, 3.6, 1H), 3.88 (dd, J 12.7, 3.4,
1H), 3.85 (dd, J 11.0, 3.6, 1H), 3.78–3.72 (m,2H), 3.52(dd, J 11.2,
9.6, 1H), 3.08 (ddd, J 12.7, 8.7, 5.7, 1H), 2.97 (dt, J 12.7, 2.7, 1H).
dC (125 MHz, CDCl3) 136.9, 136.1, 135.0, 134.9, 128.6, 128.3,
128.2, 127.8, 127.4, 127.3, 68.3, 68.1, 64.3, 60.4, 48.6. HRMS
Anal. Calc. for C19H20NO: 278.1539; found: 278.1532.
N-Ethyl-2-hydroxy-N-methylethan-1-amine N-oxide (12)
1-N-(2-Hydroxyethyl)-2-methyl-3,4-diphenyl-1H-pyrrole
(7) from LDA Treatment of 6
To neat compound 13 (322 mg, 3.12 mmol) was added H2O2
(0.41 mL, 30 % aqueous solution) and the resulting mixture was
stirred overnight (20 h). Toluene was then added with vigorous
stirring, and after ,5 min the solvent was removed under high
vacuum to afford the title compound 12 (314 mg, 84 %) as a
viscous clear oil. dH (500 MHz, [D4]methanol) 4.07–3.96
(m, 2H), 3.52–3.39 (m, 4H), 3.18 (s, 3H), 1.36 (t, J 7.2, 3H).
dC (125 MHz, [D4]methanol) 70.1, 65.7, 57.2, 55.3, 8.8. HRMS
Anal. Calc. for C5H14NO2: 120.1019; found: 120.1019.
To a solution of 6 (90 mg, 0.324 mmol) in anhydrous THF
(9 mL) at 08C under an argon atmosphere, was added freshly
prepared LDA (3.0 mL, 1.14 mmol, 0.37 M THF solution) in
three portions at 30 min intervals. The reaction was quenched
15 min after the last addition using a saturated aqueous solution
of NH4Cl. The aqueous phase was extracted using EtOAc, and
the combined organic phase was dried over MgSO4. Purification
by silica column chromatography (EtOAc) afforded 7 (64 mg,
71 %, 82 % brsm) and recovered starting material 6 (12 mg).
N-Methyl-N-(2-(vinyloxy)ethyl)hydroxylamine (14)
and 2,3-dimethyloxazolidine 3-N-oxide (15)
Dimorpholinomethane (16)
A suspension of NMO (4) (137 mg, 1.17 mmol) and diphenyl
acetylene (208 mg, 1.17 mmol) in anhydrous THF (10 mL) was
treatedwithKHMDS(9.36 mL, 0.5 M intoluene)at 08Cunderan
argon atmosphere. The reaction was stirred at this temperature
for a period of 1 h and a further 24 h at r.t. after which time the
reaction was quenched using a saturated aqueous solution of
NH4Cl. The aqueous phase was extracted using EtOAc, dried
over MgSO4, and concentrated under vacuum to afford
hydroxylamine 14 as a crude oil. dH (500 MHz, [D6]benzene)
6.47 (dd, J 14.3, 6.6, 1H, 14), 4.25 (dd, J 14.3, 1.8, 1H, 14),
4.18–4.12(m, 1H, 15), 3.97(dd, J 6.6, 1.8, 1H, 14), 3.83(brs, 2H,
14), 3.71 (q, J 5.5, 1H, 15), 3.43 (ddd, J 10.5, 7.2, 3.3, 1H, 15),
3.23 (dt, J 8.1, 3.3, 1H, 15), 2.76 (br t, J 5.5, 2H, 14), 2.53 (br s,
3H, 14), 2.45 (s, 3H, 15), 2.46–2.39 (m, 1H, 15), 1.32 (d, J 5.5,
3H, 15). dC (125 MHz, [D6]benzene) 152.6 (14), 100.1 (15), 86.4
(14), 67.0 (15), 66.5 (14), 64.2 (15), 61.6 (14), 52.6 (14), 49.7
(15), 13.0(15). Compound 14 converts to 15 in chloroform-d and
[D6]benzene; thus, only a mixture could be observed by NMR.
The crude oil was dissolved in CHCl3 (used as obtained from
supplier) and stirred for a period of 20 h at r.t. after which time
the solvent was removed under vacuum and the crude material
washed with light petroleum to afford oxazolidine N-oxide 15
(110mg, 80%) as a pale solid. dH (500MHz, CDCl3) 4.64 (q, J
5.5, 1H), 4.46 (dt, J 8.6, 7.3, 1H), 4.06 (dt, J 8.6, 4.0, 1H), 3.79
(ddd, J10.9, 7.2, 3.9, 1H), 3.71–3.63(m, 1H), 3.20(s, 3H), 1.54(d,
J 5.5, 3H). dC (125 MHz, CDCl3) 100.4, 67.6, 63.9, 53.3, 12.6.
HRMS Anal. Calc. for C5H12NO2: 118.0863; found: 118.0858.
To a suspension of NMO (4) (412 mg, 3.51 mmol) in anhydrous
THF (20 mL) under an argon atmosphere, was added MDA
(7.54 mL, 5.27 mmol, 0.7 M THF solution) dropwise over a
period of 15 min. The reaction was quenched 1 h after the
addition using a saturated aqueous solution of NH4Cl. The
aqueous phase was extracted using EtOAc and the combined
organic phase was dried over MgSO4 to afford 16 in a crude
yield of ,70 %. The NMR spectra were in accordance with
those reported previously.[24]
Supplementary Material
Copies of 1H and 13C NMR spectra, further discussion of
computational studies of mechanism, and a compilation of
computational data can be found in the Supplementary Material.
Acknowledgements
We thank the Australian Research Council and the University of Queensland
for financial support. C.M.W. and E.H.K. are ARC Future Fellows supported
by grants FT110100851 and FT120100632, respectively. Computational
resources were provided by the National Facility of the National Compu-
tational Infrastructure through the Merit Allocation Scheme, and by the
University of Queensland Research Computing Centre.
References
[1] (a) I. Coldham, R. Hufton, Chem. Rev. 2005, 105, 2765. doi:10.1021/
7,8-Diphenyl-3,4,6,8a-tetrahydro-1H-pyrrolo[2,1-c]
[1,4]oxazine (6)
To a suspension of NMO (4) (252 mg, 2.15 mmol) and diphenyl
acetylene (383 mg, 2.15 mmol) in anhydrous THF (14 mL) at
08C under an argon atmosphere, was added MDA (9.22 mL,
6.45 mmol, 0.7 M THF solution) dropwise over a period of