The [2,3] sigmatropic rearrangement of N-benzyl-O-allylhydroxylamines

Article abstract of DOI:10.1039/b205323n

The rearrangement of a range of N-benzyl-O-allylhydroxylamines to the corresponding N-allylhydroxylamines upon treatment with n-BuLi in THF, followed by reduction to the corresponding N-allylamines, is described. Mechanistic studies of the transformation are consistent with an intramolecular [2,3] sigmatropic rearrangement.

Full text of DOI:10.1039/b205323n

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The [2,3] sigmatropic rearrangement of N-benzyl-O-
allylhydroxylamines
Stephen G. Davies,* John F. Fox, Simon Jones, Anne J. Price, Miguel A. Sanz,
Thomas G. R. Sellers, Andrew D. Smith and Fátima C. Teixeira
1
The Dyson Perrins Laboratory, University of Oxford, South Parks Road, Oxford,
UK OX1 3QY
Received (in Cambridge, UK) 31st May 2002, Accepted 19th June 2002
First published as an Advance Article on the web 12th July 2002
The rearrangement of a range of N-benzyl-O-allylhydroxylamines to the corresponding N-allylhydroxylamines upon
treatment with n-BuLi in THF, followed by reduction to the corresponding N-allylamines, is described. Mechanistic
studies of the transformation are consistent with an intramolecular [2,3] sigmatropic rearrangement.
reverse rearrangement of N-aryl-N-allylhydroxylamines 3 to
O-allylhydroxylamines 4 has also been recently communicated
Introduction
Sigmatropic rearrangement processes have been used exten-
(Fig. 2).15
sively within organic synthesis for a variety of synthetic
applications. Of the many rearrangement processes that exist,1
[2,3] sigmatropic rearrangements have received considerable
attention as a method for carbon–carbon and carbon–
heteroatom bond formation.2 A variety of substrates have
been shown to undergo this transformation,3 including the
Sommelet–Hauser rearrangement of quaternary ammonium
salts,4 the Meisenheimer rearrangement of tertiary amine
oxides,5 the Mislow rearrangement of allylic sulfoxides6 and the
related Wittig and aza-Wittig rearrangements of allylic ethers7
and amines8 (Fig. 1).
Fig. 2 [2,3] Sigmatropic N,O rearrangements.
The recent rediscovery16,17 of this novel N,O [2,3] sigmatropic
rearrangement protocol, which we first reported four years
ago,18 has prompted us to report herein our full mechanistic
investigations concerning the [2,3] sigmatropic rearrangement
of N-benzyl-O-allylhydroxylamines to N-benzyl-N-allyl-
hydroxylamines.
Results and discussion
Preparation of N-benzyl-O-allylhydroxylamine substrates
To investigate fully the substrate limitations of this rearrange-
ment, an efficient route for the preparation of a range of
substituted N,O-disubstituted hydroxylamines was required.
Fig. 1 [2,3] Sigmatropic rearrangements.
As a result of the synthetic utility of these transformations,9
The most widely used approach for the synthesis of such
there is an ongoing demand for novel rearrangement processes
substrates involves the reduction of O-substituted oximes,
that facilitate the preparation of highly functionalised inter-
mediates. During our investigations concerning the preparation
which in turn may be readily prepared by O-alkylation of
oximes.19 In this manner, treatment of benzaldehyde oxime
of homochiral hydroxylamine chromium tricarbonyl com-
with KOtBu in THF and subsequent alkylation with either
allyl, crotyl†, 3-methylbut-2-enyl, (E)-cinnamyl, 1-methylallyl
or 1-methylbut-2-enyl halides respectively gave the O-allyl
oximes 5–10 in good to excellent yields after purification by
distillation or chromatography.20 Although O-cinnamyl oxime
8 was isolated as a single geometric isomer using this alkylation
protocol, the crotyl and 1-methyl-but-2-enyl bromides were
plexes,10 and the continuation of our lithium amide studies11 we
noticed an unusual rearrangement of N-benzyl-O-allylhydroxyl-
amines such as 1 to the corresponding N-benzyl-N-allyl-
hydroxylamines 2. This process was assumed to arise from an
intramolecular [2,3] sigmatropic rearrangement, formally
analogous to the [2,3] Wittig rearrangement. Related processes
have been reported in the literature, notably involving the
rearrangement of allyl oxime ethers to nitrones under both
thermal12,13 and palladium() catalyzed conditions,14 while the
† The IUPAC name for crotyl is but-2-enyl.
DOI: 10.1039/b205323n
J. Chem. Soc., Perkin Trans. 1, 2002, 1757–1765
This journal is © The Royal Society of Chemistry 2002
1757

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supplied as 76 : 24 or 83 : 17 mixtures of (E) and (Z) isomers
respectively, and so 6 and 10 were isolated as a corresponding
mixture of isomers. Similar treatment of acetophenone oxime
with allyl bromide gave O-allyl oxime 11 in high yield. While a
number of reducing agents have previously been employed for
the reduction of oximes,21,22 in our hands O-allyl oximes 5–11
were readily reduced with pyridine–borane, to give the desired
N-benzyl-O-allylhydroxylamines 12–18 in excellent overall
yields (Scheme 1).
Scheme 2 Reagents and conditions: (i) n-BuLi (1.1 eq.), solvent, Ϫ78
ЊC to rt, 10 minutes; (ii) n-BuLi (2 eq.), solvent, Ϫ78 ЊC to rt, 10
minutes; (iii) n-BuLi (10 eq.), solvent, Ϫ78 ЊC to rt, 10 minutes.
Scheme 1 Reagents and conditions: (i) KOtBu, THF then alkyl halide;
(ii) pyridine–borane (3 eq.), 0 ЊC to rt.
[2,3] Sigmatropic rearrangements—initial investigations
With a range of N-benzyl-O-allylhydroxylamines 12–18 in
hand, the optimal reaction conditions required for the
rearrangement were investigated, with (E)-N-benzyl-O-(3-
phenylallyl)hydroxylamine 15 initially used for model studies.
Preliminary results used n-BuLi (1.1 eq.) at Ϫ78 ЊC to initiate
the rearrangement, and toluene as the reaction solvent. Upon
warming to rt, the total consumption of starting material was
Scheme 3 Reagents and conditions: (i) n-BuLi (1.1 eq.), solvent, Ϫ78
ЊC to rt, 10 minutes; (ii) n-BuLi (5 eq.), solvent, Ϫ78 ЊC to rt, 10
minutes; (iii) n-BuLi (10 eq.), solvent, Ϫ78 ЊC to rt, 10 minutes.
1
noted after 10 minutes. H NMR spectroscopic analysis of the
crude reaction mixture showed a 1 : 1 : 1 mixture of three
components, identified as the required rearrangement products
N-benzyl-N-(1-phenylallyl)hydroxylamine 19, cinnamyl alcohol
20 and N-benzyl-N-butylamine 21.23 N-Benzyl-N-butylamine
21 presumably arises from the direct displacement of the
alkoxide group from the intermediate lithium amide with
n-BuLi, an electrophilic amination protocol which has been
extensively studied by Beak et al.24 Indeed, treatment of
hydroxylamine 15 with an excess (2 eq. and 10 eq.) of n-BuLi in
toluene gave cinnamyl alcohol 20 and N-benzyl-N-butylamine
21 as the predominant products (71% and 83% respectively)
over the rearrangement product 19 (29% and 17% respectively).
However, exclusive formation of the rearrangement product 19
was noted if the rearrangement process was carried out with
n-BuLi (1.1 eq.) in either THF or Et2O (Scheme 2).
Similar treatment of N-benzyl-O-allylhydroxylamine 12
with 1.1 eq. n-BuLi showed predominant rearrangement to
N-benzyl-N-allylhydroxylamine 22 in either toluene, THF or
Et2O, although N-benzyl-N-butylamine 21 was the major
product observed upon addition of excess (5 eq. and 10 eq.)
of n-BuLi in toluene (Scheme 3).
Further investigations concentrated upon identification of
the optimal base required for activation of the rearrange-
ment of (E)-N-benzyl-O-(3-phenylallyl)hydroxylamine 15 to
N-benzyl-N-(1-phenylallyl)hydroxylamine 19, with MeMgBr
t
or BuOK leading to significant substrate decomposition, and
no isolable or identifiable products. n-BuLi was found to be
essential to effect total and exclusive conversion to the
rearrangement product 19, while the use of LiHMDS or
NaHMDS gave predominantly the rearrangement product
19, but also significant quantities of cinnamyl alcohol 20
(Scheme 4).
Subsequent optimisation studies therefore used n-BuLi as the
base and THF as the reaction solvent, and concentrated upon
elucidating the effect of temperature on the rearrangement,
using N-benzyl-O-allylhydroxylamine 12. Thus, treatment of
hydroxylamine 12 in THF with n-BuLi at either Ϫ78 ЊC, Ϫ61
ЊC, Ϫ43 ЊC, Ϫ20 ЊC or 0 ЊC for one hour prior to work-up
indicated that the reaction had proceeded to 0%, 20%, 78%,
>95% and >95% conversion respectively to N-benzyl-N-
allylhydroxylamine 22. Monitoring the extent of conversion
of N-benzyl-O-allylhydroxylamine 12 to N-benzyl-N-allyl-
hydroxylamine 22 with time at Ϫ43 ЊC showed that the reaction
obeyed first order kinetics, with a rate constant k = 0.024
minϪ1 corresponding to a half life of the rearrangement of
approximately 30 minutes. Further optimisation led to a more
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J. Chem. Soc., Perkin Trans. 1, 2002, 1757–1765

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of (E)-N-benzyl-N-but-2-enylhydroxylamine 25.26 This is con-
sistent with the reaction occurring via an envelope transition
state, with the C(1) methyl group preferentially occupying a
pseudo-equatorial position, consistent with that proposed for
the related [2,3] Wittig rearrangement (Fig. 3).
Scheme 4 Reagents and conditions: (i) base, THF, Ϫ78 ЊC to rt, 10
minutes.
Fig. 3
convenient general reaction protocol, whereby deprotonation
of amine 12 with n-BuLi at Ϫ78 ЊC for one hour, prior to
warming to rt for 30 minutes, then addition of water gave the
rearranged product in essentially quantitative conversion as
determined by 1H NMR spectroscopic analysis.25 Use of
this optimised experimental procedure with hydroxylamine
substrates 12–18 gave the rearranged products 19, 22–27 as
the sole reaction products in excellent conversion (>95%).
The only problematic reaction of those studied was the
attempted rearrangement of N-benzyl-O-(3-methylbut-2-
enyl)hydroxylamine 14 involving rearrangement to a tertiary
centre, which proceeded to give only 10% of the desired
product 24, even after deprotonation and stirring at rt for 48 h.
However, by heating the reaction to reflux for 2 h after the
initial addition of n-BuLi at Ϫ78 ЊC, the reaction could be
driven to complete conversion to the desired hydroxylamine 24.
Attempted Kugelröhr distillation of the product N-benzyl-N-
allylhydroxylamines resulted in extensive product decom-
position, while purification by chromatography on silica
typically gave <30% mass recovery. While unsatisfactory, the
use of silica doped with 1% NEt3 consistently furnished the best
mass return (40% to 61% yield) of the purified hydroxylamines,
although still in a noticeably lower isolated yield than that
expected from the quantitative conversion observed from the
1H NMR spectrum of the crude material (Scheme 5).
Reduction of hydroxylamine products
Although the rearrangement of hydroxylamines 12–18 had
proceeded to excellent levels of conversion, the moderate
isolated yields of compounds 19, 22–27 were inadequate for
practical preparative use. However, reduction of the N–O bond
of hydroxylamines 19, 22–27 could be easily performed using
Zn and HCl to afford the corresponding allylic amines, which
proved more amenable to purification. In this manner the
desired allylic amines 28–34 were obtained in good to excellent
yields and high purity (Scheme 6).
The success of this reduction protocol suggested that it
would be convenient to perform the hydroxylamine reduction
on the crude rearranged products. Thus, rearrangement of
hydroxylamines 12, 13 and 15 and direct reduction of the
crude reaction mixture gave allylic amines 28, 29 and 31 in
excellent yields (91%, 93% and 92% respectively) over two
steps (Scheme 7).
This ‘one-pot’ protocol involving rearrangement and
direct reduction therefore provides a versatile route to α-
functionalised allylic amines that have previously proved to
be useful synthons in organic synthesis.27
Further mechanistic investigations
Information regarding the transition state of this reaction
was obtained from the rearrangement of N-benzyl-O-(1-methyl-
allyl)hydroxylamine 16, which results in the exclusive formation
Further mechanistic investigations were performed to confirm
that the reaction was indeed a [2,3] rearrangement process, since
the related rearrangement of N,O-disubstituted hydroxylamine
Scheme 5 Reagents and conditions: (i) n-BuLi, THF, Ϫ78 ЊC then rt; (ii) n-BuLi, THF, Ϫ78 ЊC then ∆.
J. Chem. Soc., Perkin Trans. 1, 2002, 1757–1765
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isolation of the crude reaction mixture, only components 23
and 27 were observed, consistent with the respective intra-
molecular rearrangement processes, providing further con-
vincing evidence that the mechanism of the reaction was an
intramolecular [2,3] sigmatropic process (Scheme 8).
Scheme 6 Reagents and conditions: (i) Zn, HCl, 80 ЊC.
Scheme 8 Reagents and conditions: (i) n-BuLi, THF, Ϫ78 ЊC then rt.
Conclusion
In conclusion, a range of N-benzyl-O-allylhydroxylamines
can be converted to the corresponding N-allylamines by a
protocol consisting of an intramolecular [2,3] sigmatropic
rearrangement and subsequent reduction with Zn and HCl.
Further studies investigating diastereo- and enantioselective
[2,3] sigmatropic N–O rearrangements are currently underway
in our laboratory.
Scheme 7 Reagents and conditions: (i) n-BuLi, THF, Ϫ78 ЊC then rt;
(ii) Zn, HCl.
35 to N,N-disubstituted hydroxylamine 37 has been shown to
proceed via a [1,2] anionic process (Fig. 4).28
Experimental
General
All reactions described as being carried out under nitrogen
were performed using standard vacuum line techniques, using
glassware that was flame-dried. Reactions described as being
performed at Ϫ78 ЊC were cooled by means of an acetone–dry
ice bath, those at Ϫ61 ЊC by a chloroform slush bath, those at
Ϫ43 ЊC by an acetonitrile slush bath, those at Ϫ20 ЊC by an
ethylene glycol slush bath, and those at 0 ЊC by an ice bath.
THF was distilled from sodium benzophenone ketyl under
nitrogen prior to use. n-Butyllithium was used as a solution in
hexanes and was titrated against diphenylacetic acid prior to
use. All other reagents were used as supplied, without further
purification. Column chromatography was performed on silica
gel (Kieselgel 60), and neutral deactivated silica gel (Kieselgel
60, deactivated with 1% NEt3). Thin layer chromatography was
performed on Merck plates, either aluminium sheets coated
with 0.2 mm silica gel 60 F254, or glass plates coated with 0.25
mm silica gel 60 F254. Plates were visualised either by UV
light (254 nm), phosphomolybdic acid (10% in ethanol) or
potassium permanganate (1% solution in 2% aqueous acetic
acid, containing 7% potassium carbonate). Infra-red spectra
were recorded using a Perkin-Elmer Paragon 1000 FT spec-
trometer. Selected peaks are reported. NMR spectra were
recorded on Varian Gemini 200 (1H 200 MHz, 13C 50 MHz),
Bruker AC 200 (1H 200 MHz, 13C 50 MHz), Bruker DPX 400
(1H 400 MHz, 13C 100 MHz), Bruker AM 500 (1H 500 MHz,
13C 125 MHz), or Bruker AMX 500 (1H 500 MHz, 13C 125
MHz) spectrometers. Chemical shifts (δH) are reported in
parts per million and are referenced to the residual solvent
peak. Coupling constants (J) are recorded in Hz. Low
resolution mass spectra were recorded using a VG MASSLAB
20–250 instrument, with the major peaks listed with intensities
quoted as percentages of the base peak. Accurate mass
measurements were recorded on a VG Autospec instrument,
Fig. 4
However, for the rearrangement of hydroxylamines 12–18
this [1,2] type process was discounted, as the reaction of crotyl
hydroxylamine 13 gave exclusively the [2,3] rearrangement
product 23. No trace of N-benzyl-N-crotylhydroxylamine 25,
the expected product arising from a [1,2] process, was observed
in this reaction (Fig. 5).
Fig. 5
The possibility of the mechanism proceeding either via an
intermolecular rearrangement or dissociation of a radical
pair was similarly ruled out by performing a crossover
experiment with substrates 13 and 18. Thus, an equimolar
mixture of 13 and 18 was treated with 2 eq. of n-BuLi under
the standard rearrangement conditions and the reaction
mixture was analysed by 1H NMR spectroscopy. If an
intermolecular process was occurring, rather than an intra-
molecular reaction, the scrambled products of rearrangement
22 and 38 would be observed alongside 23 and 27. After
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and were conducted by Mr R. Procter of the Dyson Perrins
Laboratory. Retention times were recorded on a Pye 104
analytical GC, using nitrogen carrier gas (40 cm3 minϪ1).
Peaks were detected by flame ionisation and are reported in
minutes. Elemental analyses were obtained by Mr R. Prior of
the Dyson Perrins analytical department on a Carla Erba 1106
combustion elemental analyser. Although compounds 8, 9, 11,
12, 18, 19, 22, 29 and 33 have been noted previously in the
literature, varying degrees of experimental data have been
reported; full characterisation of these materials is described
herein.
m/z (APCI) 190 (MHϩ, 5%), 122 (100%); HRMS calculated
for C12H16NOϩ: 190.1232. Found: 190.1239.
(E )-Benzaldehyde O-(3-phenylallyl)oxime 829
From benzaldehyde oxime (2.00 g, 16.5 mmol) and cinnamyl
bromide (4.88 g, 24.8 mmol), the oxime 8 (3.25 g, 83%) was
obtained as a colourless oil after column chromatography
(1% Et2O–hexane, SiO2) which solidified on standing to give a
cream coloured solid (mp 42–43 ЊC); νmax(film)/cmϪ1 3027 (s),
1952 (w), 1879 (w), 1810 (w); δH (200 MHz, CDCl3) 5.02 (2H,
dd, J 1.1, 6.1, CH CH᎐CH), 6.59 (1H, dt, J 16.0, 6.1, CH CH᎐
᎐
᎐
2
2
CH), 6.85 (1H, d, J 16.0, CH CH᎐CH ), 7.38–7.59 (8H, m,
aromatic CH ), 7.72–7.78 (2H, m, aromatic CH ), 8.31 (1H, s,
᎐
2
General procedure for the preparation of O-allyl oximes
Potassium tert-butoxide (1 eq.) was added to a 0.1 M solution
of oxime (1.1 eq.) in THF at 0 ЊC and stirred for 20 min under
nitrogen. A solution of the allyl bromide (1.5 eq., 0.1 M in
THF) was added via cannula to the resulting white suspension
with stirring over 5 min, before warming to room temperature
and stirring for a further hour. The resulting mixture was
partitioned between distilled water and diethyl ether, the
combined organic extracts dried (MgSO4) and concentrated
in vacuo. The resulting yellow oil was purified by short path
distillation at reduced pressure, or column chromatography.
CH᎐N); δ (50 MHz, CDCl ) 75.1 (CH CH᎐CH), 125.4, 126.8,
127.2, 128.0, 128.7, 128.8, 129.9, 133.5 (aromatic and alkene
᎐
᎐
C
3
2
CH), 132.4, 136.8 (ipso-C), 149.0 (CH᎐N); m/z (APCI) 238
᎐
(MHϩ, 5%), 117 (PhCH᎐CHCH ϩ, 100%); HRMS calculated
᎐
2
for C16H15NO: C 81.0, H 6.4, N 5.9%. Found: C 80.8, H 6.4, N
5.75%.
Benzaldehyde O-(1-methylallyl)oxime 930
Benzaldehyde oxime (1.01 g, 8.34 mmol) and potassium tert-
butoxide (1.02 g, 9.09 mmol) were dissolved in THF (40 ml).
After stirring for 20 min, 3-chlorobut-1-ene (1.7 ml, 16.5 mmol)
was added in a dropwise manner over five minutes. Sodium
bromide (849 mg, 8.25 mmol) and tetrabutylammonium
chloride (115 mg, 0.41 mmol) were then added, and the mixture
refluxed for 18 h. After cooling, water (40 ml) was added, and
the mixture extracted with diethyl ether (2 × 40 ml), dried
(MgSO4), and the solvents removed in vacuo. Short path
distillation (bp 68 ЊC, 0.2 mmHg) gave the oxime 9 (980 mg,
68%) as a pale yellow oil. νmax(film)/cmϪ1 2983 (s), 1879 (w); δH
(400 MHz, CDCl3) 1.41 (3H, d, J 6.4, CH3), 4.80 (1H, app
Benzaldehyde O-allyloxime 5
From benzaldehyde oxime (5.00 g, 45.4 mmol) and allyl
bromide (7.50 g, 62.0 mmol), the oxime 5 was obtained (6.03 g,
91%) as a colourless oil after short path distillation (bp 90 ЊC, 4
mmHg; lit.,13 bp 90 ЊC, 8 mmHg); νmax/cmϪ1 (film) 2921 (s), 1956
(w), 1880 (m), 1648 (m); δH (200 MHz, CDCl3) 4.69 (2H, app dt,
J 5.8, 1.4, OCH ), 5.27 (1H, ddt, J 10.4, 1.7, 1.1, CH᎐CHH),
᎐
2
5.37 (1H, app dq, J 17.3, 1.6, CH᎐CHH ), 6.07 (1H, ddt, J
᎐
17.3, 10.4, 5.8, CH᎐CH ), 7.34–7.44 (3H, m, aromatic CH ),
᎐
2
7.55–7.63 (2H, m, aromatic CH ), 8.13 (1H, s, CH᎐N); δ
᎐
C
quintet t, J 6.4, 1.1, CH CH ), 5.19 (1H, app dt, J 10.6, 1.3, CH᎐
᎐
3
(50 MHz, CDCl ) 75.2 (CH O), 118.0 (CH ᎐CH), 127.1, 128.8,
᎐
2
3
2
CHH), 5.30 (1H, app dt, J 17.3, 1.4, CH᎐CHH ), 5.99 (1H, ddd,
᎐
129.9 (aromatic CH), 132.3 (ipso-C), 134.2 (CH ᎐CH), 148.9
᎐
2
J 17.3, 10.7, 6.2, CH᎐CH ), 7.35–7.41 (3H, m, aromatic CH ),
᎐
2
(CH᎐N); m/z (APCI) (MHϩ, 25%), 131 (65%), 106 (100%);
᎐
7.57–7.61 (2H, m, aromatic CH ), 8.11 (1H, s, CH᎐N); δ
᎐
C
HRMS calculated for C10H12NOϩ: 162.0919. Found: 162.0922.
(50 MHz, CDCl3) 19.8 (CH3), 80.1 (CH3CH), 115.8
(CH᎐CH ), 127.1, 128.7, 129.7 (aromatic CH), 132.6 (ipso-C),
᎐
2
139.5 (CH᎐CH ), 148.5 (CH᎐N); m/z (APCI) 176 (MHϩ, 10%),
Benzaldehyde O-(but-2-enyl)oxime 6
᎐
᎐
2
122 (PhCHNOH2ϩ, 100%); HRMS calculated for C11H14NOϩ:
176.1075. Found: 176.1072.
From benzaldehyde oxime (2.00 g, 16.5 mmol) and crotyl
bromide (3.35 g, 24.8 mmol), the oxime 6 (2.28 g, 86%) was
obtained as a colourless oil (E : Z 76 : 24) after short path
distillation (bp 94 ЊC, 4 mmHg; lit.,13 bp 52 ЊC, 0.5 mmHg);
νmax/cmϪ1 (film) 2917 (s), 1882 (w), 1674 (m); δH (500 MHz,
CDCl3) 1.76 (3H, dd, J 6.4, 1.2, CH3), 4.63 (2H, d, J 6.5, (E)-
Benzaldehyde O-(1-methylbut-2-enyl)oxime 10
Phosphorus tribromide (0.53 ml, 5.6 mmol) was added in a
dropwise manner to a solution of (E)-pent-3-en-2-ol (1.53 ml,
15 mmol) in diethyl ether (50 ml), cooled to 0 ЊC. The mixture
was stirred for 24 h, and then used in the next step without
purification. Benzaldehyde oxime (2.43 g, 20 mmol) and
potassium tert-butoxide were dissolved in THF (50 ml) at 0 ЊC.
After 30 min, the solution of bromide was transferred to the
mixture by cannula, and the resulting mixture heated to reflux
for 18 h. After cooling, water (50 ml) was added, the mixture
extracted with diethyl ether (3 × 50 ml), dried (MgSO4), and
the solvent removed in vacuo. Column chromatography
(10% Et2O–petrol (40–60), SiO2) gave the oxime 10 (1.22 g,
43%) as a colourless oil (E : Z 83 : 17). Data for major (E)-
isomer; νmax/cmϪ1 (film) 2979 (s), 1890 (w), 1676 (m); δH (400
MHz, CDCl3) 1.39 (3H, d, J 6.4, CH3), 1.74 (3H, app d, J 6.7,
CH3), 4.75 (1H, app quintet, J 6.5, OCH ), 5.58–5.66 (1H, m,
CH᎐CH), 5.73–5.82 (1H, m, CH᎐CH ), 7.32–7.40 (3H, m,
OCH ), 4.77 (2H, d, J 6.6, (Z)-OCH ), 5.71–5.77 (1H, m, CH᎐
᎐
2
2
CHCH ), 5.82–5.87 (2H, m, CH᎐CHCH ), 7.36–7.41 (3H, m,
᎐
3
3
aromatic CH ), 7.58–7.61 (2H, m, aromatic CH ), 8.11 (1H, s,
CH᎐N); δ (50 MHz, CDCl ) 13.1 ((Z)-CH ), 17.8 ((E)-CH ),
᎐
C
3
3
3
69.6 ((Z)-CH2), 75.1 ((E)-CH2), 125.8, 126.8, 127.1, 127.2,
128.6, 128.8, 129.2, 129.9. 131.0 ((E)- and (Z)-aromatic CH
and CH᎐CH), 132.5 (ipso-C), 148.8 (CH᎐N); m/z (APCI) 176
᎐
᎐
(MHϩ, 15%), 122 (100%); HRMS calculated for C11H14NOϩ:
176.1075. Found: 176.1074.
Benzaldehyde O-(3-methylbut-2-enyl)oxime 7
From benzaldehyde oxime (2.00 g, 18.2 mmol) and 3-
methylbut-2-enyl bromide (3.70 g, 24.8 mmol), the oxime 7
(2.78 g, 89%) was obtained as a colourless oil after short path
distillation (bp 100–102 ЊC, 1 mmHg); νmax/cmϪ1 (film) 2931 (s),
1954 (w), 1879 (w), 1812 (w), 1676 (s); δH (400 MHz, CDCl3)
1.77 (3H, s, CH3), 1.80 (3H, s, CH3), 4.70 (2H, d, J 7.2, OCH2),
5.50 (1H, tsept, J 7.2, 1.3, OCH2CH ), 7.36–7.41 (3H, m,
aromatic CH ), 7.56–7.60 (2H, m, aromatic CH ), 8.10 (1H, s,
CH᎐N); δ (50 MHz, CDCl3) 18.1 (CH3), 25.8 (CH3), 70.9
᎐
᎐
aromatic CH ), 7.57–7.60 (2H, m, aromatic CH ), 8.09 (1H, s,
CH᎐N); δ (50 MHz, CDCl3) 17.9 (CH3), 20.1 (CH3), 79.9
᎐
C
(CH CHCH᎐CH), 127.0, 127.7, 128.6, 129.5, 132.3 (CH᎐CH,
᎐
᎐
3
CH᎐CH and ArCH), 132.7 (ipso-C), 148.1 (CH᎐N); m/z
᎐
᎐
(APCI) 190 (MHϩ, 15%), 122 (PhCHNOH2ϩ, 100%), 106
(10%); HRMS calculated for C12H16NOϩ: 190.1232. Found:
190.1228.
᎐
C
(CH O), 120.1 (CH᎐C(CH ) ), 127.2, 128.9, 129.9 (aromatic
᎐
2
3 2
CH), 132.7, 138.7 (ipso-C and CH᎐C(CH ) ), 148.7 (CH᎐N);
᎐
᎐
3
2
J. Chem. Soc., Perkin Trans. 1, 2002, 1757–1765
1761

View Article Online
Acetophenone O-allyloxime 1110
(PhCH2NHOH2ϩ, 20%), 107 (100%), 106 (MHϩ Ϫ CH CH᎐
᎐
3
CHCH2OH, 70%); HRMS calculated for C11H16NOϩ:
178.1232; Found: 178.1232.
From acetophenone oxime (1.00 g, 7.40 mmol) and allyl
bromide (0.98 g, 8.14 mmol), the oxime 11 (1.21 g, 93%) was
obtained as a colourless oil after short path distillation (bp 95
ЊC, 4 mmHg; lit.,31 89 ЊC, 6 mmHg); δH (500 MHz, CDCl3) 2.28
(3H, s, CH3), 4.73 (2H, app dt, J 5.7, 1.4, OCH2), 5.25 (1H, app
N-Benzyl-O-(3-methylbut-2-enyl)hydroxylamine 14
From oxime 7 (2.50 g, 13.2 mmol) and pyridine–borane
complex (3.69 g, 39.7 mmol) using method A, 14 (2.02 g, 80%)
was obtained as a colourless oil by column chromatography
(25% Et2O–petrol (40–60), SiO2). νmax/cmϪ1 (film) 3258 (m),
2914 (s), 1949 (w), 1876 (w), 1809 (w), 1674 (s), 1604 (w); δH
(200 MHz, CDCl3) 1.67 (3H, s, CH3), 1.76 (3H, s, CH3), 4.08
(2H, s, PhCH2), 4.18 (2H, d, J 7.1, OCH2), 5.35 (1H, tsept,
J 7.1, 1.4, OCH2CH ), 5.72 (1H, br s, NH ), 7.28–7.42 (5H, m,
aromatic CH ); δC (50 MHz, CDCl3) 17.9 (CH3), 25.7 (CH3),
dq, J 10.4, 1.3, CH᎐CHH), 5.36 (1H, app dq, J 17.3, 1.6, CH᎐
᎐
᎐
CHH ), 6.09 (1H, ddt, J 17.3, 10.4, 5.7, CH᎐CH ), 7.35–7.41
(3H, m, aromatic CH ), 7.53–7.68 (2H, m, aromatic CH ).
᎐
2
General procedure for the reduction of the oxime ethers
Method A: pyridine–borane complex (3 eq.) was added to a
stirred 0.5 M solution of the allylic oxime (1 eq.) in absolute
ethanol at 0 ЊC, followed by the dropwise addition of a solution
of 10% HCl in water (4 ml per mmol of oxime) over a period of
five minutes. The mixture was warmed to room temperature
and stirred for a further 1 h after which time the mixture was
cooled to 0 ЊC, saturated aqueous sodium carbonate solution
added until the acid was neutralised, and the mixture extracted
with dichloromethane. The combined organic extracts were
dried (MgSO4), concentrated in vacuo and the resulting yellow
oil purified by reduced pressure short path distillation to give
the desired hydroxylamine.
Method B: pyridine–borane complex (3 eq.) was added to a
stirred 0.5 M solution of the allylic oxime (1 eq.) in absolute
ethanol at 0 ЊC, followed by the dropwise addition of a solution
of 20% HCl in absolute ethanol (2 ml per mmol of oxime)
over a period of five minutes. The mixture was warmed to
room temperature and stirred for a further 24 h, then cooled
and a saturated solution of sodium carbonate added until
the acid was neutralised. The mixture was extracted with
dichloromethane, the combined organic extracts dried
(MgSO4) and concentrated in vacuo, and the residue purified by
short path distillation at reduced pressure or by column
chromatography.
56.5 (PhCH ), 70.5 (CH O), 120.4 (CH᎐C(CH ) ), 127.6,
᎐
2
2
3 2
128.6, 129.2 (aromatic CH), 138.0, 138.2 (ipso-C and CH᎐
᎐
C(CH3)2); m/z (APCI) 192 (MHϩ, 60%), 179 (55%), 136 (25%),
124 (80%), 108 (100%), 106 (80%); HRMS calculated for
C12H18NOϩ: 192.1388. Found: 192.1380.
(E )-N-Benzyl-O-(3-phenylallyl)hydroxylamine 15
From oxime 8 (3.9 g, 16.5 mmol) and pyridine–borane complex
(4.7 g, 50.5 mmol) using method B, 15 (3.32 g, 84%) was
obtained as a colourless oil by column chromatography
(33% Et2O–petrol (40–60), SiO2) which solidified on standing to
give a cream solid (mp 35–36 ЊC). νmax/cmϪ1 (film) 3260 (m),
3208 (s), 1950 (w), 1878 (w), 1807 (w), 1657 (w), 1599 (m), 1578
(m); δH (400 MHz, CDCl3) 4.11 (2H, s, PhCH2), 4.33 (2H, dd,
J 6.4, 1.3, OCH2), 5.78 (1H, s, NH ), 6.27 (1H, dt, J 15.9, 6.4,
CH᎐CHCH ), 6.59 (1H, d, J 15.9, CH᎐CHCH ), 7.23–7.40
᎐
᎐
2
2
(10H, m, aromatic CH ); δC (50 MHz, CDCl3) 56.7 (PhCH2),
74.8 (CH2O), 125.7, 126.6, 127.5, 127.7, 128.5, 128.6, 129.1,
133.2 (CH᎐CH and aromatic CH), 136.8, 137.6 (ipso-C): m/z
᎐
(APCI) 240 (MHϩ, 5%), 133 (75%), 117 (30%), 105 (100%);
calculated for C16H17NO: C 80.3, H 7.2, N 5.85. Found: C 80.1,
H 7.0, N 5.65%.
N-Benzyl-O-allylhydroxylamine 1221
N-Benzyl-O-(1-methyl-allyl)hydroxylamine 16
From oxime 5 (2.0 g, 12.4 mmol) and pyridine–borane complex
(3.5 g, 37.2 mmol) using method A, 12 (1.90 g, 94%) was
obtained as a colourless oil after short path distillation (bp
110 ЊC, 4 mmHg); νmax/cmϪ1 (film) 3260, 1645, 1454, 1421; δH
(500 MHz, CDCl3) 4.08 (2H, s, PhCH2), 4.18 (2H, app dt, J
From oxime 9 (878 mg, 5.02 mmol) and pyridine–borane
complex (1.9 ml, 15 mmol) using method B, 16 (614 mg, 69%)
was obtained as a colourless oil by column chromatography
(30% Et2O–petrol (40–60), SiO2); νmax/cmϪ1 (film) 3259 (m),
2980 (s), 1950 (w), 1871 (w), 1811 (w), 1642 (w), 1604 (w); δH
(400 MHz, CDCl3) 1.20 (3H, d, J 6.7, CH3), 4.11 (2H, s,
5.9, 1.3, OCH ), 5.18 (1H, app dq, J 10.4, 1.3, CH᎐CHH), 5.26
᎐
2
(1H, app dq, J 17.3, 1.6, CH᎐CHH ), 5.70 (1H, br s, NH ), 5.91
᎐
(1H, ddt, J 17.3, 10.4 and 5.9, CH᎐CH ), 7.28–7.38 (5H, m,
PhCH ), 4.14 (1H, m, CH CH ), 5.12 (1H, d, J 10.4, CH᎐
᎐
2 3
᎐
2
aromatic CH ); δC (50 MHz, CDCl3) 56.2 (PhCH2), 74.8
CHH), 5.20 (1H, app dt, J 17.3, 1.3, CH᎐CHH ), 5.54 (1H, br s,
᎐
(OCH ), 117.3 (CH᎐CH ), 127.3, 128.2, 128.8 (aromatic CH),
NH ), 5.81 (1H, ddd, J 17.3, 10.4, 6.7, CH᎐CH ), 7.26–7.37
(5H, m, aromatic CH ); δC (50 MHz, CDCl3) 19.4 (CH3), 56.8
᎐
᎐
2
2
2
134.6 (CH᎐CH ), 137.6 (ArC); m/z (APCI) 164 (MHϩ, 100%),
᎐
2
108 (PhCH2NH3ϩ, 11%), 106 (PhCHNH2ϩ, 22%); calculated
for C10H13NO: C 73.6, H 8.0, N 8.6%. Found: C 73.9, H 8.1,
N 9.0%.
(PhCH ), 79.7 (CHCH ), 115.9 (CH᎐CH ), 127.6, 128.6,
᎐
2
3
2
129.4 (aromatic CH), 137.9 (ipso-C), 140.4 (CH᎐CH ); m/z
᎐
2
(APCI) 178 (MHϩ, 100%), 124 (PhCH2NH2OHϩ, 15%), 107
(15%); HRMS calculated for C11H16NOϩ: 178.1232. Found:
178.1229.
N-Benzyl-O-(but-2-enyl)hydroxylamine 13
From oxime 6 (1.83 g, 10.4 mmol) and pyridine–borane
complex (2.92 g, 31.2 mmol) using method A, 13 (1.56 g, 85%)
was obtained as a colourless oil (E : Z 76 : 24) by short path
distillation (bp 112 ЊC, 4 mmHg); νmax/cmϪ1 (film) 3259 (m),
2915 (s), 1950 (w), 1877 (w), 1808 (w), 1673 (m), 1604 (m); δH
(400 MHz, CDCl3) 1.64 (3H, ddt, J 6.8, 1.7, 0.8, (Z)-CH3), 1.71
(3H, app dq, J 6.4, 1.3, (E)-CH3), 4.07 (2H, s, (E)-PhCH2),
4.08 (2H, s, (Z)-PhCH2), 4.10 (2H, app dquintet, J 6.5, 1.1,
(E)-OCH2), 4.24 (2H, m, (Z)-OCH2), 5.52–5.56 (1H, m,
N-Benzyl-O-(1-methylbut-2-enyl)hydroxylamine 17
From oxime 10 (432 mg, 2.29 mmol) and pyridine–borane
complex (0.86 ml, 6.86 mmol) using method B, 17 (356 mg,
82%) was obtained as a colourless oil (E : Z 83 : 17) by column
chromatography (10% Et2O–petrol (40–60), SiO2); νmax/cmϪ1
(film) 3258 (m), 2973 (s), 1948 (w), 1878 (w), 1808 (w), 1674 (m),
1604 (m); δH (400 MHz, CDCl3) 1.16 (3H, d, J 6.4, (Z)-
OCHCH3), 1.18 (3H, d, J 6.5, (E)-OCHCH3), 1.65 (3H, dd,
(E)- and (Z)-CH᎐CHCH ), 5.56–5.76 (2H, m, (E)- and (Z)-
J 6.9, 1.8, (Z)-CH᎐CHCH ), 1.69 (3H, ddd, J 6.4, 1.5, 0.6,
᎐
3
᎐
3
CH᎐CHCH and NH ), 7.26–7.39 (5H, m, aromatic CH ); δ
(E)-CH᎐CHCH ), 4.04 (2H, s, (E)-PhCH ), 4.05 (2H, s, (Z)-
᎐
3 2
᎐
3
C
(125 MHz, CDCl3) 13.1 ((Z)-CH3), 17.8 ((E)-CH3), 56.4
(NCH2), 69.1 ((Z)-OCH2), 74.6 ((E)-OCH2), 126.0, 126.8,
PhCH2), 4.09 (1H, m, (E)-OCHCH3), 4.52 (1H, dqd, J 8.7, 6.4,
1.1, (Z)-OCHCH ), 5.35 (1H, ddq, J 11.0, 8.7, 1.8, (Z)-CH᎐
᎐
3
127.0, 127.3, 128.3, 128.5, 128.9, 130.3 (aromatic CH and CH᎐
CHCH ), 5.41 (1H, ddq, J 15.4, 7.4, 1.5, (E)-CH᎐CHCH ),
᎐
3 3
᎐
CH), 137.5 (ipso-C); m/z (APCI) 178 (MHϩ, 40%), 124
5.48 (1H, br s, NH ), 5.58 (1H, dqd, J 11.0, 6.9, 1.1, (Z)-CH᎐
᎐
1762
J. Chem. Soc., Perkin Trans. 1, 2002, 1757–1765

View Article Online
CHCH ), 5.65 (1H, dqd, J 15.4, 6.4, 0.9, (E)-CH᎐CHCH ),
7.28–7.37 (5H, m, aromatic CH ); δC (50 MHz, CDCl3) 17.8
(CH3), 19.8 (CH3), 56.7 (PhCH2), 79.1 (CH3CH), 127.3,
app quintet, J 6.9, CHCH3), 3.69 (1H, d, J 13.3, PhCHH), 3.87
(1H, d, J 13.3, PhCHH ), 5.18 (1H, d, J 17.5, CH᎐CHH), 5.20
᎐
3
3
᎐
(1H, d, J 10.4, CH᎐CHH ), 5.45 (1H, br s, OH ), 5.97 (1H, ddd,
᎐
127.4, 128.3, 129.1, 133.0 (CH᎐CH and aromatic CH), 137.7
J 17.5, 10.4, 7.5, CH᎐CH ), 7.25–7.44 (5H, m, aromatic CH );
δC (125 MHz, CDCl3) 17.5 (CH3), 60.7 (PhCH2), 64.6
᎐
᎐
2
(ipso-C); m/z (APCI) 192 (MHϩ, 10%), 179 (40%), 124
(PhCH2NH2OHϩ, 100%); HRMS calculated for C12H18NOϩ:
192.1388. Found: 192.1396.
(CHCH ), 116.8 (CH᎐CH ), 127.2, 128.2, 129.7 (aromatic
᎐
3
2
CH), 137.9 (ipso-C), 138.4 (CH᎐CH ); m/z (APCI) 178 (MHϩ,
᎐
2
100%), 176 (10%), 162 (C11H16Nϩ, 31%), 160 (C11H14Nϩ, 29%),
124 (PhCH2NH2OHϩ, 58%), 122 (PhCH2NOHϩ, 8%), 106
N-(1-Phenylethyl)-O-allylhydroxylamine 1810
ϩ
(PhCHNH2
,
46%); HRMS calculated for C11H16NOϩ:
From allyl oxime 11 (1.21 g, 6.91 mmol) and pyridine–borane
complex (2.40 g, 20.7 mmol) using method B, 18 (1.02 g, 83%)
was obtained as a colourless oil by short path distillation
(bp 104 ЊC, 4 mmHg). δH (500 MHz, CDCl3) 1.39 (3H, d, J 6.7,
CH3), 4.11 (1H, dd, J 12.6, 5.9, OCHH), 4.17 (1H, dd, J 12.6,
5.9, OCHH ), 4.17 (1H, q, J 6.7, CH3CH ), 5.16 (1H, app d, J
178.1232. Found: 178.1233.
N-Benzyl-N-(1,1-dimethylallyl)hydroxylamine 24
Addition of n-butyllithium (1.66 M, 0.79 ml, 1.31 mmol) to the
hydroxylamine 14 (250 mg, 1.31 mmol) gave, after stirring at
Ϫ78 ЊC for 1 h, then heating at reflux for 2 h, the hydroxylamine
24 (119 mg, 60%) as a yellow oil after chromatography
(10% Et2O–petrol (40–60), SiO2). νmax/cmϪ1 (film) 3536 (s), 3442
(br, m), 1640 (m), 1606 (m); δH (200 MHz, CDCl3) 1.31 (6H, s,
C(CH3)2), 3.75 (2H, s, PhCH2), 4.81 (1H, s, OH ), 5.17 (1H, d,
10.4, CH᎐CHH), 5.23 (1H, app dq, J 17.3, 1.5, CH᎐CHH ),
᎐
᎐
5.61 (1H, br s, NH ), 5.88 (1H, ddt, J 17.3, 10.4, 5.9, CH᎐CH ),
᎐
2
7.26–7.38 (5H, m, aromatic CH ).
General procedure for the rearrangement reaction
J 10.8, CH᎐CHH), 5.21 (1H, d, J 17.8, CH᎐CHH ), 5.97
᎐
᎐
n-Butyllithium (1.1–1.3 eq.) was added to a 0.1 M solution of
hydroxylamine (1 eq.) in anhydrous THF at Ϫ78 ЊC under
nitrogen. After stirring for 1 h the reaction was allowed to warm
to room temperature and was stirred for a further 30 min. The
reaction was quenched with distilled water, extracted with
diethyl ether, the combined organic extracts dried (MgSO4) and
concentrated in vacuo. The residue was purified by column
chromatography on deactivated silica gel (1% Et3N in petrol) to
give the desired hydroxylamine rearrangement product.
(1H, dd, J 17.8, 10.8, CH᎐CH ), 7.26–7.35 (5H, m, aromatic
᎐
2
CH ); δC (50 MHz, CDCl3) 22.8 (C(CH3)2), 57.1 (PhCH2), 63.1
(C(CH ) ), 113.6 (CH᎐CH ), 127.1, 128.5, 129.5 (aromatic
᎐
3
2
2
CH), 139.9 (ipso-C), 144.1 (CH᎐CH ); m/z (APCI) 192 (MHϩ,
᎐
2
15%), 159 (40%), 124 (100%); HRMS calculated for
C12H18NOϩ: 192.1388. Found: 192.1380.
(E )-N-Benzyl-N-(but-2-enyl)hydroxylamine 25
Addition of n-butyllithium (2.5 M, 0.52 ml, 1.31 mmol) and the
hydroxylamine 16 (211 mg, 1.19 mmol) gave the hydroxylamine
25 (115 mg, 55%) as a colourless oil after chromatography
(10% Et2O–petrol (40–60), SiO2); νmax/cmϪ1 (film) 3222 (s), 2917
(s), 1949 (w), 1878 (w), 1809 (w), 1671 (w), 1604 (w); δH
(400 MHz, CDCl3) 1.72 (3H, d, J 5.9, CH3), 3.33 (2H, d, J 6.2,
N-Benzyl-N-(1-phenylallyl)hydroxylamine 1933
Addition of n-butyllithium (1.66 M, 1.26 ml, 2.09 mmol) and
the hydroxylamine 15 (500 mg, 2.09 mmol) gave the hydroxy-
lamine 19 (201 mg, 40%) as a cream solid (mp 91–92 ЊC) after
chromatography (10% Et2O–petrol (40–60), SiO2). νmax/cmϪ1
(KBr disc) 3213 (m), 2866 (s); δH (400 MHz, CDCl3) 3.77
(1H, d, J 13.6, PhCHH), 3.91 (1H, br d, PhCHH ), 4.31 (1H, d,
J 8.5, NCHPh), 4.65 (1H, br s, OH ), 5.25 (1H, dd, J 10.0, 1.3,
NCH CH), 3.78 (2H, s, NCH Ph), 5.57–5.65 (2H, m, CH CH᎐
᎐
2
2
2
CH and OH ), 5.70 (1H, dq, J 15.4, 5.9, CH CH᎐CH ), 7.24–
᎐
2
7.36 (5H, m, aromatic CH ); δC (50 MHz, CDCl3) 17.8 (CH3),
61.4, 63.4 (PhCH2 and CH CH᎐CH), 126.4, 127.5, 128.4,
᎐
2
CH᎐CHH), 5.31 (1H, d, J 17.3, CH᎐CHH ), 6.18 (1H, ddd,
᎐
᎐
130.2, 130.4 (CH᎐CH and aromatic CH), 137.2 (ipso-C); m/z
᎐
J 17.3, 10.0, 8.5), 7.21–7.53 (10H, m, aromatic CH ); δC
(100 MHz, CDCl ) 61.1 (PhCH ), 75.3 (PhCH), 117.9 (CH᎐
(APCI) 178 (MHϩ, 100%), 160 (MHϩ Ϫ H2O, 15%), 147 (30%),
᎐
3
2
124 (PhCH NH OHϩ, 55%), 106 (PhCH᎐NH ϩ, 35%); HRMS
᎐
2
2
2
CH2), 127.3, 127.5, 128.2, 128.3, 128.7, 129.6 (aromatic CH),
calculated for C12H18NOϩ: 178.1232. Found: 178.1232.
137.7 (CH᎐CH ), 138.0, 141.0 (ipso-C); m/z (CI) 240 (MHϩ,
᎐
2
100%), 224 (32%), 222 (MHϩ Ϫ H O, 27%), 117 (PhCHCH᎐
᎐
2
CH2ϩ, 45%); HRMS calculated for C16H17NOϩ: 240.1388.
Found: 240.1383.
N-Benzyl-N-(1-methylbut-2-enyl)hydroxylamine 26
Addition of n-butyllithium (2.5 M, 0.76 ml, 1.90 mmol) to the
hydroxylamine 17 (330 mg, 1.73 mmol) gave the hydroxylamine
26 (183 mg, 55%) as a colourless oil after chromatography
(10% Et2O–petrol (40–60), SiO2). νmax/cmϪ1 (film) 3234 (br s),
2974 (s), 1948 (w), 1876 (w), 1809 (w), 1752 (w), 1667 (m), 1605
(m); δH (400 MHz, CDCl3) 1.24 (3H, d, J 6.5, NCHCH3), 1.74
(3H, d, J 4.9, CH᎐CHCH ), 3.28 (1H, app quintet, J 6.6,
N-Benzyl-N-allylhydroxylamine 2232
Addition of n-butyllithium (1.66 M, 0.96 ml, 1.60 mmol) to the
hydroxylamine 12 (200 mg, 1.23 mmol) gave the hydroxylamine
22 (122 mg, 61%) as a yellow oil after chromatography (10%
Et2O–petrol (40–60), SiO2); νmax/cmϪ1 (film) 3217, 1644, 1494,
᎐
3
NCHCH3), 3.65 (1H, d, J 13.2, NCHH), 3.87 (1H, d, J 13.2,
1453; δH (500 MHz, CDCl ) 3.36 (2H, d, J 6.5, NCH CH᎐),
᎐
3
2
NCHH ), 5.32–5.51 (1H, br s, OH ), 5.53–5.66 (2H, m, CH᎐
3.79 (2H, s, NCH Ph), 5.20 (1H, app d, J 10.3, CH᎐CHH), 5.24
᎐
᎐
2
CH ), 7.23–7.36 (5H, m, aromatic CH ); δC (50 MHz, CDCl3)
18.0 and 18.1 (CH3), 60.6 (PhCH2), 63.8 (CH3CH), 127.1,
(1H, app dq, J 17.2, 1.4, CH᎐CHH ), 5.95 (1H, ddt, J 17.2, 10.3,
᎐
6.5, CH᎐CH ), 7.27–7.35 (5H, m, aromatic CH ); δ (125 MHz,
᎐
2
C
128.0, 128.2, 129.7, 131.1 (CH᎐CH and aromatic CH), 138.0
CDCl ) 62.4, 63.7 (NCH Ph and NCH CH᎐), 118.7 (CH᎐
᎐
᎐
᎐
3
2
2
ϩ
(ipso-C); m/z (APCI) 192 (MHϩ, 20%), 124 (PhCH2NHOH2
,
CH ), 127.4, 128.2, 129.9 (aromatic CH), 133.7 (CH᎐CH ),
᎐
2
2
100%); HRMS calculated for C12H18NOϩ: 192.1388. Found:
192.1389.
136.9 (ipso-C); m/z (APCI) 164 (MHϩ, 100%), 148 (7%);
HRMS calculated for C10H14NOϩ: 164.1075. Found: 164.1067.
N-Benzyl-N-(1-methylallyl)hydroxylamine 23
N-(1-Phenylethyl)-N-allylhydroxylamine 2710
Addition of n-butyllithium (2.59 M, 0.48 ml, 1.24 mmol) to the
hydroxylamine 13 (200 mg, 1.13 mmol) gave the hydroxylamine
23 (118 mg, 59%) as a yellow oil after chromatography (10%
Et2O–petrol (40–60), SiO2). νmax/cmϪ1 (film) 3236, 1639, 1496,
1454; δH (500 MHz, CDCl3) 1.26 (3H, d, J 6.6, CH3), 3.33 (1H,
Addition of n-butyllithium (2.10 M, 0.60 ml, 1.24 mmol) to the
hydroxylamine 18 (200 mg, 1.13 mmol) gave the hydroxylamine
27 (105 mg, 53%) as a yellow oil after chromatography (10%
Et2O–petrol (40–60), SiO2); δH (500 MHz, CDCl3) 1.49 (3H, d,
J 6.6, CH3), 3.25–3.31 (2H, m, NCH2), 3.83 (1H, q, J 6.6,
J. Chem. Soc., Perkin Trans. 1, 2002, 1757–1765
1763

View Article Online
CH CH ), 5.18 (1H, d, J 10.9, CH᎐CHH), 5.18 (1H, d, J
obtained as a pale yellow oil. νmax/cmϪ1 (film) 3168 (br m), 2971
(s), 1947 (w), 1874 (w), 1808 (w), 1668 (w), 1604 (m); δH
(400 MHz, CDCl3) 1.16 (3H, d, J 6.6, NCHCH3), 1.71 (3H, dd,
᎐
3
17.3, CH᎐CHH ), 5.98 (1H, m, CH᎐CH ), 7.26–7.40 (5H, m,
᎐
᎐
2
aromatic CH ).
J 6.4, 1.6, CH᎐CHCH ), 3.18 (1H, app quintet, J 6.9,
᎐
3
General procedure for the reduction of the hydroxylamines
NCHCH3), 3.68 (1H, d, J 13.1, PhCHH), 3.79 (1H, d, J 13.1,
PhCHH ), 5.35 (1H, ddq, J 15.2, 7.9, 1.6, CH᎐CHCH ), 5.55
᎐
3
Hydroxylamine (1 eq.) was dissolved in 2 M HCl (10 ml) and
zinc powder added (5 eq.) cautiously. The reaction was then
heated at 80 ЊC for 1 h, cooled and neutralised with 2 M NaOH.
The white suspension obtained was extracted with Et2O and
dried (MgSO4). Evaporation afforded the allylic amine that was
determined to be >95% pure from the 1H NMR spectrum.
(1H, dqd, J 15.2, 6.4, 0.7, CH᎐CHCH ), 7.22–7.37 (5H, m,
᎐
3
aromatic CH ); δ (100 MHz, CDCl ) 17.7 (CH᎐CHCH ), 22.0
᎐
C
3
3
(NCHCH ), 51.3 (NCH ), 55.2 (NCHCH ), 125.8 (CH᎐CH),
᎐
3
2
3
126.8, 128.2, 128.4 (aromatic CH), 135.4 (CH᎐CH), 140.7
᎐
(ipso-C); m/z (APCI) 175 (MHϩ, 5%), 163 (10%), 124 (20%),
108 (PhCH2NH2ϩ, 100%); calculated for C12H18Nϩ: 176.1439.
Found: 176.1438.
N-Benzyl-N-allylamine 2834
From hydroxylamine 22 (100 mg, 0.61 mmol) and zinc powder
(200 mg, 3.1 mmol), the desired amine 28 (81 mg, 90%) was
obtained as a colourless oil. δH (200 MHz, CDCl3) 3.29 (2H, dt,
N-(1-Phenylethyl)-N-allylamine 3440
From hydroxylamine 27 (100 mg, 0.56 mmol) and zinc powder
(183 mg, 2.8 mmol), the desired amine 34 (85 mg, 94%) was
obtained as a colourless oil. δH (200 MHz, CDCl3) 1.39 (3H, d,
J 6.6, CH3), 1.92 (1H, br s, NH ), 3.11 (2H, d, J 6.0, NCH2),
J 6.0, 1.4, CH CH᎐CH ), 3.80 (2H, s, PhCH ), 5.10–5.26
᎐
2
2
2
(2H, m, CH᎐CH ), 5.95 (1H, ddt, J 17.2, 10.3, 6.0, CH᎐CH ),
᎐
᎐
2
2
7.21–7.36 (5H, m, aromatic CH ).
3.82 (1H, q, J 6.6, CHCH ), 5.08 (1H, ddt, J 10.2, 1.9, 1.3, CH᎐
᎐
3
CHH), 5.14 (1H, app dq, J 17.2, 1.6, CH᎐CHH ), 5.91 (1H, ddt,
᎐
N-Benzyl-N-(1-methylallyl)amine 2935
J 17.2, 10.2, 6.0, CH᎐CH ), 7.22–7.40 (5H, m, aromatic CH ).
᎐
2
From hydroxylamine 23 (100 mg, 0.564 mmol) and zinc powder
(183 mg, 2.82 mmol), the desired amine 29 (85 mg, 94%) was
obtained as an oil. νmax/cmϪ1 (film) 3318 (w), 2962 (s), 1640 (w),
1605 (w); δH (500 MHz, CDCl3) 1.20 (3H, d, J 6.5, CH3), 1.52,
(1H, br s, NH ), 3.24 (1H, app quintet, J 6.8, CH3CH ), 3.70
(1H, d, J 13.1, PhCHH), 3.82 (1H, d, J 13.1, PhCHH ), 5.10
Acknowledgements
The authors wish to acknowledge the support of the EPSRC
for a studentship and the SCI for a Messel scholarship
(T. G. R. S.) and New College, Oxford for a Junior Research
Fellowship (A. D. S.) and Fundação para a Ciência e a Tecno-
logia (Programa Praxis XXI) for funding (F. C. T.).
(1H, dd, J 10.2, 1.5, CH᎐CHH), 5.15 (1H, app d, J 17.2,
᎐
CH᎐CHH ), 5.74 (1H, ddd, J 17.2, 10.2, 7.7, CH᎐CH ),
᎐
᎐
2
7.23–7.36 (5H, m, aromatic CH ); δC (125 MHz, CDCl3) 21.7
(CH ), 51.3 (PhCH ), 56.0 (CHCH ), 114.7 (CH᎐CH ), 126.8,
᎐
3
2
3
2
References
128.1, 128.4 (aromatic CH), 140.5 (ipso-C), 142.4 (CH᎐CH );
᎐
2
m/z (APCI) 162 (MHϩ, 100%), 108 (5%); calculated for
1 For selected reviews concerning sigmatropic rearrangements see
K. Neuschütz, J. Velker and R. Neier, Synthesis, 1998, 227;
D. Enders, M. Knopp and R. Schiffers, Tetrahedron: Asymmetry,
1996, 7, 1847; A. W. Murray, Org. React. Mech., 1997, 473;
C. W. Spangler, Chem. Rev., 1976, 76, 187.
C11H16Nϩ: 162.1283. Found: 162.1284.
N-Benzyl-N-(1,1-dimethylallyl)amine 3036
From hydroxylamine 24 (51 mg, 0.27 mmol) and zinc powder
(88 mg, 1.36 mmol), the desired amine 30 (43 mg, 92%) was
obtained as an oil. δH (200 MHz, CDCl3) 1.25 (6H, s, C(CH3)2),
2 For reviews see T. Nakai and K. Mikami, Chem. Rev., 1986, 86, 885;
K. Mikami and T. Nakai, Synthesis, 1991, 594; R. W. Hoffmann,
Angew. Chem., Int. Ed. Engl., 1979, 18, 563; A. H. Li, L. X. Dai
and V. K. Aggarwal, Chem. Rev., 1997, 97, 2341.
3.65 (2H, s, PhCH ), 5.08–5.16 (2H, m, CH᎐CH ), 5.86 (1H, dd,
᎐
2
2
3 For related rearrangement processes see J. E. Baldwin and R. E.
Peavy, Tetrahedron Lett., 1968, 5029; J. E. Baldwin, J. DeBernardis
and J. E. Patrick, Tetrahedron Lett., 1970, 353; J. E. Baldwin and
F. J. Urban, J. Chem. Soc., Chem. Commun., 1970, 165; J. E. Baldwin
and J. E. Patrick, J. Am. Chem. Soc., 1971, 93, 3556; J. E. Baldwin
and W. F. Erickson, J. Chem. Soc., Chem. Commun., 1971, 359.
4 For selected manuscripts see C. R. Hauser, R. M. Manyik,
W. R. Brasen and P. L. Bayless, J. Org. Chem., 1955, 20, 1119;
C. L. Bumgardner, J. Am. Chem. Soc., 1963, 85, 73; S. H. Pine,
Tetrahedron Lett., 1967, 3393; W. Q. Beard and C. R. Hauser, J. Org.
Chem., 1960, 25, 334; W. Q. Beard and C. R. Hauser, J. Org. Chem.,
1961, 26, 371; G. C. Jones, W. Q. Beard and C. R. Hauser, J. Org.
Chem., 1963, 28, 199; S. J. Campbell and D. Darwish, Can. J. Chem.,
1976, 54, 193; M. Nakano and Y. Sato, J. Org. Chem., 1987, 52,
1844; H. Sugiyama, Y. Sato and N. Shirai, Synthesis, 1988, 988;
T. Tanaka, N. Shirai, J. Sugimori and Y. Sato, J. Org. Chem., 1992,
57, 5034.
J 17.8, 10.4, CH᎐CH ), 7.23–7.34 (5H, m, aromatic CH ); δ
᎐
2
C
(50 MHz, CDCl3) 26.8 (2 × CH3), 47.5 (PhCH2), 54.7
(C(CH ) ), 112.5 (CH᎐CH ), 127.0, 128.4, 128.5 (aromatic
᎐
3
2
2
CH), 141.3 (ipso-C), 146.2 (CH᎐CH ).
᎐
2
N-Benzyl-N-(1-phenylallyl)amine 3137
From hydroxylamine 19 (100 mg, 0.42 mmol) and zinc powder
(140 mg, 2.1 mmol), the desired amine 31 (85 mg, 91%) was
obtained as a yellow oil. δH (400 MHz, CDCl3) 1.69 (1H, s,
NH ), 3.73 (1H, d, J 13.3, PhCHH), 3.76 (1H, d, J 13.3,
PhCHH ), 4.24 (1H, d, J 7.1, CHCH᎐CH ), 5.14 (1H, d, J 10.1,
᎐
2
CH᎐CHH), 5.24 (1H, d, J 17.1, CH᎐CHH ), 5.97 (1H, ddd, J
᎐
᎐
17.1, 10.1, 7.1, CH᎐CH ), 7.24–7.54 (10H, m, aromatic CH ).
᎐
2
5 For [2,3] Meisenheimer rearrangements see A. Guarna, E. G.
Occhiato, M. Pizzetti, D. Scarpi, S. Sisi and M. van Sterkenburg,
Tetrahedron: Asymmetry, 2000, 11, 4227; J. Blanchet, M. Bonin,
L. Micouin and H.-P. Husson, Tetrahedron Lett., 2000, 41, 8279;
D. Enders and H. Kempen, Synlett, 1994, 969; R. Nordmann and
P. Gull, Helv. Chim. Acta, 1986, 69, 246 . For [1,2] Meisenheimer
rearrangements see H. Sashida and T. Tsuchiya, Chem. Pharm. Bull.,
1984, 32, 4117; T. Tsuchiya and H. Sashida, Heterocycles, 1980, 14,
1925.
6 P. Bickart, F. W. Carson, J. Jacobus, E. G. Miller and K. Mislow,
J. Am. Chem. Soc., 1968, 90, 4869; R. Tang and K. Mislow, J. Am.
Chem. Soc., 1970, 92, 2100; T. Sato, J. Otera and H. Nozaki, J. Org.
Chem., 1989, 54, 2779.
(E )-N-Benzyl-N-(but-2-enyl)amine 3238
From hydroxylamine 25 (109 mg, 0.615 mmol) and zinc powder
(201 mg, 3.08 mmol), the desired amine 32 (69 mg, 70%)
was obtained as a pale yellow oil. δH (400 MHz, CDCl3) 1.70
(3H, d, J 5.6, CH ), 3.22 (2H, d, J 5.4, CH CH᎐CH), 3.79
᎐
3
2
(2H, s, PhCH ), 5.55–5.66 (2H, m, CH᎐CH ), 7.25–7.33 (5H, m,
᎐
2
aromatic CH ); δC (125 MHz, CDCl3) 17.7 (CH3), 51.0, 53.1
(CH2NCH2), 126.8, 127.4, 128.1, 128.3, 129.2 (aromatic and
alkene CH), 140.2 (ipso-C).
N-Benzyl-N-(1-methylbut-2-enyl)amine 3339
7 For examples see G. Wittig and E. Stahnecker, Liebigs Ann. Chem.,
1957, 69, 605; Y. Makisumi and S. Notzumoto, Tetrahedron Lett.,
1966, 7, 6393; G. Wittig, Angew. Chem., 1954, 66, 10; U. Schöllkopf,
Angew. Chem., Int. Ed. Engl., 1970, 9, 763.
From hydroxylamine 26 (181 mg, 0.948 mmol) and zinc powder
(310 mg, 4.74 mmol), the desired amine 33 (137 mg, 83%) was
1764
J. Chem. Soc., Perkin Trans. 1, 2002, 1757–1765

View Article Online
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26 H NMR homonuclear decoupling indicated a coupling constant J
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