Regioselective aminobromination of terminal alkenes

Article abstract of DOI:10.1016/S0040-4020(03)00907-4

The addition of t-butyl N,N-dibromocarbamate (BBC) to a variety of terminal alkenes has been studied. The reaction was spontaneously initiated and proceeded smoothly in refluxing dichloromethane. The N-bromo adducts, formed upon addition, could be reduced

Full text of DOI:10.1016/S0040-4020(03)00907-4

Tetrahedron 59 (2003) 5927–5934
Regioselective aminobromination of terminal alkenesq
´
Anna Sliwinska and Andrzej Zwierzak
*
´
´ ´
Institute of Organic Chemistry, Technical University (Politechnika), Zeromskiego 116, 90-924 Łodz, Poland
Received 20 March 2003; revised 13 May 2003; accepted 5 June 2003
Abstract—The addition of t-butyl N,N-dibromocarbamate (BBC) to a variety of terminal alkenes has been studied. The reaction was
spontaneously initiated and proceeded smoothly in refluxing dichloromethane. The N-bromo adducts, formed upon addition, could be
reduced in situ with aqueous sodium sulfite to give the corresponding 2-bromo-N-Boc-amines. Immediate deprotection of these compounds
with gaseous HCl or p-toluenesulfonic acid afforded 2-bromoamine hydrochlorides or tosylates in pure state and good overall yields. The
observed regioselectivity for anti-Markovnikov addition, as proven by NMR and MS, is fully consistent with the radical-chain mechanism
proposed for the reaction.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
bromine addition products. All these facts prompted us to
investigate a new, phosphorus free reagent, t-butyl N,N-
dibromocarbamate (BBC) 3 as a better substitute of DBPA
for aminobromination of terminal alkenes.
A plethora of synthetic procedures leading to aziridines has
been described.1 However, there is still a need for a new,
simple and economic synthesis of this class of compounds
due to their interesting chemistry dominated by ring-
opening reactions. Among the methods used for the
preparation of aziridines, spontaneous cyclization of
2-bromoamines is practically meaningless because these
starting materials are almost inaccessible.
2. Results and discussion
2.1. Preparation of t-butyl N,N-dibromocarbamate
(BBC) 3
Some years ago we reported2,3 a simple two-step procedure
leading to 2-bromoamine hydrochlorides involving the free-
radical or ionic addition of diethyl N,N-dibromophosphor-
amidate (DBPA) 1 to alkenes and cycloalkenes followed by
degradation of the adducts with gaseous hydrogen chloride
(Scheme 1).
The title compound could be readily obtained in high yield
by bromination of crude t-butyl carbamate 24 contaminated
with ca. 10% of an unidentified impurity. The reaction was
carried out at room temperature by adding bromine to the
aqueous solution of t-butyl carbamate 2 containing 10%
excess of potassium carbonate. t-Butyl N,N-dibromocarba-
mate 3, isolated by extraction with dichloromethane in ca.
90% yield, was an orange solid contaminated with ca. 9% of
This approach to 2-bromoamines remained practically
unnoticed by the chemical community possibly due to the
necessary use of an organophosphorus reagent of unknown
toxicity. Moreover, the addition of DBPA 1 to less reactive
alkenes afforded rather low yields of products and often
inevitably led to complex and intractable mixtures of
compounds containing mainly allylic bromination and/or
1
t-butyl N-bromocarbamate 3a as determined by H NMR
spectroscopy (Scheme 2). Analytically pure samples of 3
(mp 93–958C) could be prepared by bromination of pure 2
(mp 107–1088C) and washing the product with cold
pentane.
Scheme 1.
q Preliminary communication: Klepacz, A.; Zwierzak, A. Tetrahedron Lett. 2001, 42, 4539–4540.
Keywords: alkenes; amines; radicals and radical reactions; deblocking.
*
Corresponding author. Tel.: þ48-42-6313146; fax: þ48-42-6365530
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00907-4

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A. Sliwinska, A. Zwierzak / Tetrahedron 59 (2003) 5927–5934
5928
isobutylene, 2-methylbut-1-ene, 3-methylbut-1-ene, pent-1-
ene, hex-1-ene, hept-1-ene, oct-1-ene, and 2,4,4-trimethyl-
pent-1-ene has been studied.
All reactions were carried out in refluxing dichloromethane
by adding dropwise the solution of BBC 3 to an equimolar
amount of the alkene. After a short induction period the
reaction was practically complete after 20 min in the case of
phenylethylenes, isobutylene and 2-methylbut-1-ene. Less
reactive alkenes added BBC 3 relatively slowly in refluxing
dichloromethane but all reactions were complete after 2 h,
which could be tested visually by reduction in the dark-red
BBC color. All additions were performed under dispersed
light and did not need any UV irradiation. In all cases except
styrene and 3-methylbut-1-ene the reactions proceeded
according to the same general course outlined in Scheme 3.
Scheme 2.
The formation of 1:1 adducts was always observed. The
reactions proceeded regioselectively in an anti-
Markovnikov fashion (see proof of structure below)
affording N-Boc-N-bromo-2-bromoalkylamines 4. Upon
reduction with 12% aqueous sodium sulfite at 5–108C the
initially formed N-bromoadducts 4 were quantitatively
transformed in situ into N-Boc-2-bromoalkylamines 5a–i.
Some crude N-Boc-2-bromoalkylamines 5b–g,i formed in
high yields could be easily purified by column chromato-
graphy, analyzed, and characterized spectroscopically.
Compounds 5a and 5h were deprotected by means of
hydrogen chloride in dichloromethane to give the corre-
sponding hydrochlorides 9a and 9h (vide infra). The adducts
of BBC 3 to (E)- and (Z)-1-phenylpropene were found to be
Scheme 3.
Scheme 4.
Scheme 5.
t-Butyl N,N-dibromocarbamate 3 was perfectly stable at
þ58C and could be stored when refrigerated for indefinite
periods of time without any signs of decomposition. The
removal of t-butyl N-bromocarbamate 3a from crude 3
before use for addition to alkenes was neither necessary nor
desirable because 3a upon reduction with aqueous sodium
sulfite was transformed into t-butyl carbamate 2, easily
removable by washing with water.
75:25 diastereomeric mixtures of erythro- and threo-
isomers† in both cases (see Section 2.5, stereochemistry of
BBC addition).
Addition of BBC 3 to styrene was disturbed by relatively
fast consecutive cyclization of the primarily formed N-Boc-
2-bromo-2-phenylethylamine 5i to 5-phenyl-oxazolidin-2-
one 6 (Scheme 4). This reaction, not observed for other
BBC-alkene adducts, involved an intramolecular SN2
displacement of the benzylic bromine in 5i. The analogous
2.2. Addition of t-butyl N,N-dibromocarbamate (BBC) 3
to terminal alkenes
†
erythro (RS and SR) and threo (RR and SS) configurations were ascribed
to both racemic diastereomeric adducts on the basis of Cahn, Ingold and
Prelog convention.5
The addition of BBC 3 to several straight and branched-
chain terminal alkenes, namely styrene, 2-phenylpropene,

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A. Sliwinska, A. Zwierzak / Tetrahedron 59 (2003) 5927–5934
´
5929
Scheme 6.
conversion of some 2-mesyloxy-N-Boc-amines into oxazo-
lidinones has been reported recently.6
Table 1. 2-Bromoalkylamine hydrochlorides (9a–i) and tosylates (10a–i)
Entry
R1
R2
(9) Yield (%)a
(10) Yield (%)a
Addition of BBC 3 to low-boiling 3-methylbut-1-ene was
performed by adding large excess (ca. 4 equiv.) of
hydrocarbon dissolved in dichloromethane to the refluxing
solution of BBC in this solvent. The reaction (Scheme 5)
which was complete in 30 min, afforded ca. 1:1 mixture of
N-Boc-2-bromo-3-methylbutylamine 7 and N-Boc-2,3-
dibromo-3-methylbutylamine 8 as determined by H NMR
spectroscopy of the respective tosylates obtained by
deprotection (vide infra).
a
b
c
d
e
f
g
h
i
Ph
Me
Me
Pr
Me
Me
Et
H
H
H
H
H
H
51
78
80
60
54.5
54
52
55
–
76
75
66
60
60
58
44
86
Bu
C5H11
C6H13
Neo-C5H11
Ph
1
88
a
Yields of crude, analytically pure products.
Compound 8 was probably produced by allylic bromination
of the tertiary hydrogen atom in the starting hydrocarbon
followed by BBC addition to 3-bromo-3-methylbut-1-ene
thus formed.
2.4. Proof of structure of BBC (3) adducts of terminal
alkenes
All BBC 3 adducts of terminal alkenes 5a–i and/or their
degradation products 9,10b–i were satisfactorily analyzed
for C, H, and N. Regioisomeric purity was evident from 1H
NMR spectra examination and could be further confirmed
by detailed analysis of these spectra (see Section 4). The
anti-Markovnikov orientation of the adducts 5a–i was
unequivocally established by mass spectrometry of
2-bromoalkylamine hydrochlorides 9a–i and tosylates
10b–i. The mass spectra of 9a–i and 10b–i showed
distinct a-cleavage fragmentation giving [CH2 vNH2]%
ions, m/z¼30, in accord with the regioselectivity shown in
Scheme 7.
2.3. Deprotection of N-Boc-2-bromoalkylamines (5a–i).
Preparation of 2-bromo-alkylamine hydrochlorides
(9a–i) and tosylates (10b–i)
All crude BBC adducts to terminal alkenes 5a–i could be
easily and effectively deprotected to the corresponding
2-bromoalkylamine hydrochlorides 9a–i by treatment with
gaseous hydrogen chloride in dichloromethane at room
temperature for 24 h. Alternative degradation with
p-toluenesulfonic acid in boiling dichloromethane was
faster (1 h) and more convenient (Scheme 6). The
hydrochlorides 9a–i and tosylates 10b–i obtained on
evaporation of solvent and addition of ether to the residue
separated from the solution in pure state leaving all
impurities in the mother liquor. Overall yields of 2-bromo-
alkylamine hydrochlorides 9a–i and tosylates 10b–i were
within the range 50–85%. All compounds were analytically
pure. Their yields are collected in the Table 1. All melting
points of 2-bromoalkylamine hydrochlorides 9a–i were
substantially higher than described previously.2
Such a pattern would not be obtained for the salts 9 and 10
with the amino function at the non-terminal, secondary or
tertiary position. The anti-Markovnikov orientation of the
adducts 5a–i could be also corroborated by the absence in
MS spectra of 9a–i and 10b–i characteristic peaks at
m/z¼M2CH2Br, corresponding to the expected preferential
a-cleavage fragmentation of the regioisomeric
Markovnikov adducts.
Scheme 7.

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5930
2.5. Stereochemistry of BBC (3) addition to 1-
phenylpropenes
Diastereomeric (E)- and (Z)-1-phenylpropenes7 were
selected as model compounds for studying the stereo-
chemical course of BBC 3 addition. Both crude BBC
adducts to (E)- and (Z)-1-phenylpropene 11a and 11b have
1
superimposable H NMR spectra, suggesting that they are
identical mixtures of erythro- and threo-isomers. The
assignment of stereochemistry could not be arrived at by
1H NMR due to the complex multiplicity patterns of the
spectra. Detailed analysis was, however, possible for the 1H
NMR spectra of the respective 2-bromoamine hydro-
chlorides 12 obtained upon degradation of the crude adducts
11a and 11b with hydrogen chloride in dichloromethane.
This treatment does not change the configuration of both
chiral centers. The 1H NMR spectrum of the hydrochloride
12 obtained from (E)-1-phenylpropene adduct 11a exhibited
the presence of two doublets of different intensities centered
at d¼5.53 ppm (JHH¼5.0 Hz; higher intensity signal)
and d¼5.22 ppm (JHH¼10.0 Hz; lower intensity signal)
which could be assigned to the benzylic protons HB and
HB, in both diastereoisomers on the basis of integration,
multiplicity and chemical shifts. It is feasible to assume
the synclinal arrangement of vicinal protons HA and HB
in the preferred conformation of erythro-isomer 12a.
This would account for a smaller vicinal coupling
constant of the lower field doublet according to Karplus
relationship. The antiperiplanar arrangement of vicinal
Scheme 8.
is more stable and hence more abundant due to lesser
crowding between the methyl and phenyl groups.
2.6. Mechanism of BBC addition to terminal alkenes
0
protons HA and HB, in the preferred conformation of
All BBC additions to terminal alkenes exhibit characteristic
features indicative of spontaneously initiated8,9 free-radical
chain reactions: (i) they follow totally regioselectively
affording solely anti-Markovnikov adducts; (ii) they start
with a short induction period; (iii) the addition to non-terminal
alkenes, e.g. 1-phenylpropene is nonstereospecific. All these
phenomena can be plausibly explained by assuming a free-
radical reaction pathway presented in Scheme 9.
the threo-isomer 12b is in turn fully compatible with a
higher value of the respective coupling constant
according to Karplus equation (Scheme 8).
Almost identical spectral assignments were found for the
mixture of diastereomeric 2-bromoamine hydrochlorides 12
obtained from (Z)-1-phenylpropene adduct 11b (dHB¼5.48
ppm, JHH¼5.25 Hz; dHB¼5.19 ppm, JHH¼10.25 Hz).
Preferential formation of the erythro- adduct from both
diastereomeric alkenes can be interpreted in terms of the
existence of dynamic equilibrium between the inter-
mediately formed benzyl type radicals 12a0 and 12b0 (see
below). The radical 12a0 leading to the erythro- adduct (12a)
3. Conclusion
In conclusion we have developed a simple, two-step, and
Scheme 9.

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A. Sliwinska, A. Zwierzak / Tetrahedron 59 (2003) 5927–5934
´
5931
efficient method for regioselective aminobromination of
terminal alkenes using the new reagent-t-butyl N,N-
dibromocarbamate (3). The procedure offers an operation-
ally simple and convenient synthesis of 2-bromoamines. As
a potential route to aziridines and N-Boc-aziridines it can
successfully compete with other available protocols
involving activation of the hydroxyl group in 2-amino-
alcohols by converting into tosylates or mesylates and
subsequent ring closure by means of strong bases.10
sulphite (5 mL) was added slowly at this temperature.
Dichloromethane (15 mL) was then added, the organic layer
was separated, washed with water (3£5 mL), dried
(MgSO4) and the solvent evaporated in vacuo. The residual
crude adducts (5b–g) were purified by column chromato-
graphy using CH2Cl2 as eluent. Compounds (5a) and (5h)
decomposed on attempted purification.
4.2.1. N-Boc-2-bromo-2-methylpropylamine (5b). Yield
77%, colorless needles, mp 51–538C; [Found: C, 42.9; H,
7.4; N, 5.7. C9H18BrNO2 requires C, 42.87; H, 7.20; N,
5.55%]; Rf (CH2Cl2) 0.58; nmax (CCl4 soln) 3336, 2980,
2965, 1716, 1508, 1460, 1392, 1368, 1168, 1128 cm21; dH
5.06 (1H, bs, NH), 3.39 (2H, d, J¼6.25 Hz, CH2), 1.74 (6H,
s, Me2C), 1.46 (9H, s, Me3C); FAB/MS: 252 (14, Mþ1), 250
(14, M21) 154 (18), 152 (18), 116 (74), 73 (56), 57 (100%).
4. Experimental
4.1. General
Melting points (determined in open capillary tubes) are
uncorrected. IR spectra (liquid films or KBr discs) were
1
4.2.2. N-Boc-2-bromo-2-methylbutylamine (5c). Yield
87%, colorless solid, mp 30–328C; [Found: C, 45.0; H,
7.7; N, 5.4. C10H20BrNO2 requires C, 45.12; H, 7.58; N,
5.26%]; Rf (CH2Cl2) 0.54; nmax (film) 3300, 2980, 2935,
1708, 1515, 1450, 1400, 1375, 1255, 1175, 1135 cm21; dH
4.99 (1H, bs, NH), 3.43 (2H, d, J¼6.4 Hz, CH2NH), 1.91
(1H, q, J¼7.3 Hz, MeCH2), 1.76 (1H, q, J¼7.3 Hz,
MeCH2), 1.64 (3H, s, MeC(Br), 1.44 (9H, s, Me3C), 1.04
(3H, t, J¼7.3 Hz, MeCH2); FAB/MS: 265 (3, Mþ1), 264 (4,
M21), 168 (21), 166 (26), 136 (38), 69 (47), 57 (100%).
measured using a specord M 80 (C.Zeiss) instrument. H
NMR spectra were recorded on a Bruker AVANCE DPX-
250 spectrometer operating at 250 MHz, using CDCl3
solutions unless otherwise stated. FAB/MS were measured
on an APO Electron (Ukraine) Model MI 12001 mass
spectrometer equipped with a FAB ion source (thioglycerol
matrix). Xenon was used as ionized gas. The beam energy
was set to 5 keV. Column chromatography was performed
on silica gel 60 (Baker, 200–400 mesh). All commercially
available starting materials were purchased from Fluka and
used without additional purification.
4.2.3. N-Boc-2-bromopentylamine (5d). Yield 61%, color-
less oil; [Found: C, 45.3; H, 7.6; N, 5.1. C10H20BrNO2
requires C, 45.12; H, 7.58; N, 5.26%]; Rf (CH2Cl2) 0.74;
4.1.1. Preparation of t-butyl N,N-dibromocarbamate
(BBC, 3). Bromine (35.16 g, 0.22 mol) was added dropwise
with efficient stirring for 40 min to a solution of crude
t-butyl carbamate4 (prepared in CH2Cl2, mp 90–938C, yield
ca. 100%, purity ,90%; 12.9 g, 0.11 mol) and K2CO3
(15.2 g, 0.11 mol) in water (200 mL) at room temperature.
The resulting mixture was stirred for 2 h, CH2Cl2 (100 mL)
was then added and stirring was continued for further
15 min. The organic layer was separated, and the aqueous
phase was extracted with CH2Cl2 (3£30 mL). Combined
extracts were washed with water (30 mL), dried (MgSO4),
and the solvent evaporated in vacuo to give the title
compound 3 (24.6 g, 90%) as an orange solid. Crude 3 was
contaminated (1H NMR) with ca. 9% of t-butyl N-bromo-
carbamate. Analytically pure sample of 3 (prepared from
pure t-butyl carbamate, mp 107–1088C and washed with
cold pentane) had mp 93–958C; [Found: C, 21.7; H, 3.4; N,
5.2. C5H9O2NBr requires C, 21.84; H, 3.30; N, 5.09%]; nmax
(KBr) 2992, 1696, 1368, 1280, 1264, 1248, 1144, 872,
744 cm21; dH 1.50 (9H, s, CH3); dC 156.2, 86.2, 27.3; m/z
(CI) 274 (41, Mþ1), 276 (96, Mþ3), 278 (40, Mþ5).
n
max (film) 3360, 2990, 2960, 1710, 1520, 1465, 1400, 1380,
1255, 1175 cm21; dH 5.01 (1H, bs, NH), 4.06–4.15 (1H, m,
CHBr), 3.63 (1H, ddd, J¼14.3, 6.8, 3.8 Hz, CHBr–CH2–
NH), 3.33 (1H, ddd, J¼14.3, 7.9, 5.7 Hz, CHBr–CH2–NH),
1.79 (2H, q, J¼7.25 Hz, CH2–CH2–CHBr), 1.46 (9H, s,
Me3C), 1.38–1.63 (2H, m, CH3CH2), 0.94 (3H, t,
J¼7.25 Hz, CH3–CH2); FAB/MS: 266 (2, Mþ1), 264 (2,
M21), 168 (65), 166 (71), 57 (56), 41 (74%).
4.2.4. N-Boc-2-bromohexylamine (5e). Yield 62%, color-
less oil; [Found: C, 47.3; H, 8.1; N, 5.2. C11H22BrNO2
requires C, 47.18; H, 7.91; N, 5.00%]; Rf (CH2Cl2) 0.79;
n
max (film) 3360, 2980, 2940, 2890, 1700, 1520, 1465, 1400,
1380, 1260, 1180 cm21; dH 4.99 (1H, bs, NH), 4.04–4.14
(1H, m, CHBr–CH2), 3.63 (1H, ddd, J¼14.4, 6.6, 3.8 Hz,
CHBr–CH2–NH), 3.33 (1H, ddd, J¼14.4, 7.9, 5.5 Hz,
CHBr–CH2–NH), 1.76–1.86 (2H, m, CH2–CHBr–
CH2NH), 1.45 (9H, s, Me3C), 1.25–1.62 (4H, m,
CH3(CH2)2), 0.91 (3H, t, J¼7.1 Hz CH3CH2); FAB/MS:
182 (42), 180 (49), 144 (38), 57 (100), 43 (47), 29 (55%).
4.2. Addition of BBC (3) to terminal alkenes. General
procedure
4.2.5. N-Boc-2-bromoheptylamine (5f). Yield 58%, color-
less oil; [Found: C, 49.1; H, 8.3; N, 4.0. C12H24BrNO2
requires C, 48.99; H, 8.22; N, 4.76%]; Rf (CH2Cl2) 0.60;
A solution of BBC (3) (1.38 g, 5 mmol) in CH2Cl2 (7 mL)
was added dropwise with stirring to the solution of terminal
alkene (5 mmol) in refluxing CH2Cl2 (7 mL) for 20 min.
Stirring was then continued if necessary until pale-yellow
coloration of the solution was obtained (ca. 2 h for
compounds 5d–g). In the case of isobutylene a solution of
alkene in CH2Cl2 was added to 3 dissolved in CH2Cl2 until
disappearance of an orange color. The resulting solution
was cooled to 5–108C and 12% aqueous solution of sodium
n
max (film) 3370, 2985, 2950, 2890, 1705, 1520, 1465, 1400,
1380, 1210, 1180 cm21; dH 4.97(1H, bs, NH), 4.08–4.14(1H,
m, CHBr–CH2), 3.58–3.68 (1H, m, CHBr–CH2–NH), 3.33
(1H, ddd, J¼14.6, 8.0, 5.4 Hz, CHBr–CH2–NH), 1.76–1.85
(2H, m, CH2–CHBr–CH2NH), 1.45 (9H, s, Me3C), 1.27–
1.56 (6H, m, CH3(CH2)3), 0.89 (3H, t, J¼6.25 Hz, CH3–
CH2); FAB/MS: 296 (3, Mþ3), 294 (4, Mþ1), 292 (4, M21),
196 (82), 194 (84), 73 (32), 57 (100), 29 (43%).

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5932
4.2.6. N-Boc-2-bromooctylamine (5g). Yield 65%, color-
less oil; [Found: C, 50.5; H, 8.6; N, 4.4. C13H26BrNO2
requires C, 50.65; H, 8.50; N, 4.55%]; Rf (CH2Cl2) 0.73;
1500, 1450, 1330, 1260, 1090, 972, 948, 768, 750, 700,
656 cm21; dH (D2O) 7.33–7.49 (5H, m, Ph), 3.82 (1H, d,
J¼9.25 Hz, CH2–N) 3.77 (1H, d, J¼9.25 Hz, CH2–N),
1.79 (3H, s, Me); FAB/MS: 216 (6, MKþ2), 214 (18, MK),
178 (100), 134 (71), 91 (34), 57 (36), 30 (13%).
n
max (film) 3350, 2960, 2950, 2865, 1725, 1510, 1450, 1400,
1375, 1248, 1170 cm21; dH 4.98 (1H, bs, NH), 4.04–4.14
(1H, m, CHBr), 3.63 (1H, ddd, J¼14.4, 6.6, 3.5 Hz, CHBr–
CH2–NH), 3.32 (1H, ddd, J¼14.4, 7.9, 5.5 Hz, CHBr–
CH2–NH), 1.76–1.82 (2H, m, CH2–CHBr), 1.45 (9H, s,
Me3C), 1.28–1.52 (8H, m, CH3(CH2)4), 0.88 (3H, t,
J¼6.25 Hz, CH3–CH2); FAB/MS: 308 (6, Mþ1), 306 (4,
M21), 254 (92), 252 (100), 210 (16), 208 (24), 172 (64),
128 (22), 57 (100%).
4.5.2. 2-Bromo-2-methylpropylamine hydrochloride
(9b). Yield 78%, colorless solid, mp 157–1598C (dec.)
(EtOH–Et20); [Found: C, 25.7; H, 6.0; N, 7.6. C4H11BrClN
requires C, 25.49; H, 5.88; N, 7.43%]; nmax (KBr) 2960,
2680, 2600, 1590, 1520, 1408, 1165, 1105 cm21; dH (D2O)
3.35 (2H, s, CH2–N), 1.84 (6H, s, Me); FAB/MS: 154 (41,
MKþ2), 152 (44, MK), 137 (27), 135 (27), 72 (76), 55 (100),
41 (59), 30 (44%).
4.3. Addition of BBC (3) to styrene
The reaction was performed as described above (Section
4.2). Crude adduct was found (1H NMR) to be the mixture
containing ca. 93% of N-Boc-2-bromo-2-phenylethylamine
(5i) and 7% of 5-phenyl-oxazolidin-2-one (6). Compound
(5i) was isolated in pure state, by crystallization from
pentane. Yield 87%, colorless solid, mp 63–648C; [Found:
C, 51.9; H, 6.2; N, 4.8. C13H18BrNO2 requires C, 52.01; H,
6.04; N, 4.67%]; nmax (KBr) 3430, 3000, 1700, 1525, 1385,
1320, 1280, 1180, 1075, 950, 775, 710, 640, 600 cm21; dH
7.32–7.40 (5H, m, Ph), 5.06 (1H, t, J¼6.75 Hz, CHBr–
CH2), 4.91 (1H, bs, NH), 3.73 (2H, t, J¼6.75 Hz, CHBr–
CH2), 1.43 (9H, s, Me3C); FAB/MS: 302 (1, Mþ3), 300
(1.5, Mþ1), 246 (13), 244 (16), 202 (5), 200 (6), 164 (41),
120 (19), 91 (29), 57 (100%). The residue insoluble in hot
pentane afforded pure (6) after crystallization from water.
Colorless leaflets, mp 87–888C (Lit.,11 mp 87–898C); dH
7.37–7.42 (5H, m, Ph), 6.56 (1H, bs, NH), 5.61 (1H, dd,
J¼8.75, 7.75 Hz, CH(O)–CH2), 3.98 (1H, dt, J¼8.75,
0.75 Hz, CH(O)–CH2–NH), 3.54 (1H, ddd, J¼8.75, 7.75,
0.75 Hz, CH(O)–CH2–NH).
4.5.3. 2-Bromo-2-methylbutylamine hydrochloride (9c).
Yield 80%, colorless solid, mp 149–1508C (dec.) (EtOH–
Et2O); [Found: C, 29.8; H, 6.7; N, 7.1. C5H13BrClN requires
C, 29.65; H, 6.47; N, 6.92%]; nmax (KBr) 2950, 1588, 1514,
1450, 1420, 1395, 1152, 1105, 880 cm21; dH (D2O) 3.41
(1H, d, J¼13.8 Hz, CH2–N), 3.33 (1H, d, J¼13.8 Hz, H2,
CH2–N), 2.02 (1H, dq, J¼15.0, 7.4 Hz, CH3CH2), 1.90
(1H, dq, J¼15.0, 7.4 Hz, CH3CH2), 1.06 (3H, t, J¼7.4 Hz,
H2, CH3CH2).
4.5.4. 2-Bromopentylamine hydrochloride (9d). Yield
60%, colorless solid, mp 175–1778C (EtOH–Et2O);
[Found: C, 29.5; H, 6.5; N, 7.1. C5H13BrClN requires C,
29.65; H, 6.47; N, 6.92%]; nmax (KBr) 3160, 3065, 2010,
1600, 1508, 1410, 630 cm21; dH (D2O) 4.32 (1H, ddt,
J¼9.6, 7.0, 2.9 Hz, CH2–CH–Br–CH2), 3.50 (1H, dd,
J¼14.0, 2.9 Hz, CHBrCH2–N), 3.32 (1H, dd, J¼14.0,
9.6 Hz, CHBr–CH2–N), 1.86 (2H, q, J¼7.0 Hz, CH2CH2-
CHBr), 1.38–1.64 (2H, m, CH3CH2CH2), 0.92 (3H, t,
J¼7.4 Hz, CH3CH2); FAB/MS: 168 (83, MKþ2), 166 (87,
MK), 69 (68), 41 (100), 30 (70), 27 (50%).
4.4. Addition of BBC (3) to 3-methylbut-1-ene
4.5.5. 2-Bromohexylamine hydrochloride (9e). Yield
54.5%, colorless solid, mp 183–1858C (EtOH–Et2O);
[Found: C, 33.4; H, 7.1; N, 6.6. C6H15BrClN requires C,
33.28; H, 6.98; N, 6.47%]; nmax (KBr) 3160, 2950, 2020,
1600, 1510, 1470, 1415, 1250 cm21; dH (D2O) 4.29 (1H,
ddt, J¼9.25, 6.9, 3.25 Hz, CH2CHBrCH2), 3.50 (1H, dd,
J¼14.0, 3.25 Hz, CHBrCH2–N) 3.32 (1H, dd, J¼14.0,
9.25 Hz, CHBrCH2–N), 1.89 (2H, q, J¼6.9 Hz, CH2CH2-
CHBr), 1.31–1.53 (4H, m, CH3(CH2)2CH2), 0.89 (3H, t,
J¼7.1 Hz, CH3CH2).
The reaction was carried out by adding hydrocarbon
(40 mmol) dissolved in CH2Cl2 (20 mL) to the solution of
BBC (3, 2.76 g, 10 mmol) in the same solvent (15 mL) for
20 min at 408C. Crude adduct obtained after reduction with
sodium sulphite was a mixture containing ca. 54% of
N-Boc-2-bromo-3-methylbutylamine (7) and ca. 46% of
N-Boc-2,3-dibromo-3-methylbutylamine (8) as determined
1
by H NMR after immediate degradation with p-toluene-
sulfonic acid (vide infra).
4.5. Deprotection of (5a–i) with hydrogen chloride.
General procedure
4.5.6. 2-Bromoheptylamine hydrochloride (9f). Yield
54%, colorless leaflets, mp 181–1838C (dec.) (Me2CO);
[Found: C, 36.6; H, 7.3; N, 6.2. C7H17BrClN requires C,
35.46; H, 7.43; N, 6.08%]; nmax (KBr) 2952, 2015, 1600,
1510, 1472, 1404, 1240, 1165, 675 cm21; dH (D2O) 4.30
(1H, ddt, J¼9.5, 6.9, 3.0 Hz, CH2CHBrCH2), 3.49 (1H, dd,
J¼14.0, 3.0 Hz, CHBrCH2–N), 3.31 (1H, dd, J¼14.0,
9.5 Hz, CHBrCH2–N), 1.88 (2H, q, J¼6.9 Hz, CH2CH2-
CHBr), 1.30–1.56 (6H, m, CH3(CH2)3CH2), 0.87 (3H,
dist.t, J¼6.0 Hz, CH3CH2); FAB/MS: 196 (97, MKþ 2), 194
(100, MK), 114 (21), 55 (19), 40 (33), 30 (24), 27 (35%).
A solution of crude adduct (5a–i) prepared as described
above (Section 4.2) in CH2Cl2 (30 mL) was saturated with
gaseous hydrogen chloride at 08C and then left overnight at
room temperature. The solvent was evaporated in vacuo and
ether (30 mL) was added to the residue. Colorless crystals of
(9a–i) obtained on refrigeration for 1 h were filtered off and
washed with ether.
4.5.1. 2-Bromo-2-phenylpropylamine hydrochloride
(9a). Yield 51%, colorless plates, mp 145–1478C (EtOH–
Et20); [Found: C, 43.3; H, 5.3; N, 5.7. C9H13BrClN requires
C, 43.14; H, 5.23; N, 5.59%]; nmax (KBr) 3264, 3000, 2900,
4.5.7. 2-Bromooctylamine hydrochloride (9g). Yield
52%, colorless solid, mp 194–1968C (dec.) (EtOH–Et2O);
[Found: C, 39.1; H, 7.7; N, 5.8. C8H19BrClN requires C,

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A. Sliwinska, A. Zwierzak / Tetrahedron 59 (2003) 5927–5934
´
5933
39.28; H, 7.83; N, 5.73]; nmax (KBr) 3150, 2970, 2020,
1600, 1508, 1468, 1412, 1228, 1164, 620 cm21; dH (D2O)
4.30 (1H, ddt, J¼9.5, 7.2, 3.0 Hz, CH2CHBrCH2), 3.49 (1H,
dd, J¼14.0, 3.0 Hz, CHBrCH2–N), 3.31 (1H, dd, J¼14.0,
9.5 Hz, CHBrCH2–N), 1.87 (2H, q, J¼7.2 Hz, CH2CH2-
CHBr), 1.28–1.55 (8H, m, CH3(CH2)4CH2), 0.86 (3H,
dist.t, J¼6.8 Hz, CH3CH2).
CH3CH2); FAB/MS: 340 (7, Mþ3), 338 (8, Mþ1), 168 (96,
MKþ2), 166 (100, MK), 86 (72), 69 (50), 30 (34%).
4.6.3. 2-Bromopentylamine tosylate (10d). Yield 66%,
colorless solid, mp 125–1278C (dec.) (EtOH–Et2O);
[Found: C, 42.4; H, 6.1; N, 4.3. C12H20BrNO3S requires
C, 42.61; H, 5.96; N, 4.14%]; nmax (KBr) 3070, 1604, 1500,
1470, 1450, 1210, 1160, 1132, 1036, 1008, 822, 684,
568 cm21; dH 7.92 (3H, bs, NH3), 7.16–7.79 (4H, AA0BB0
system, C6H4), 4.03–4.19 (1H, m, CHBr–CH2), 3.24–3.33
(1H, m, CH2NH3), 2.95–3.11 (1H, m, CH2NH3), 2.36 (3H,
s, CH3C6H4), 1.61 (2H, q, J¼7.2 Hz, CH2CHBr), 1.41–1.25
(2H, nm, CH3CH2); FAB/MS: 340 (4, Mþ3), 338 (4, Mþ1),
168 (95, MKþ2), 166 (100, MK), 86 (68), 69 (71), 41 (64),
30 (69%).
4.5.8. 2-Bromo-2,4,4-trimethylpentylamine hydro-
chloride (9h). Yield 55%, colorless solid, mp 110–1128C
(EtOH–Et2O); [Found: C, 39.1; H, 7.6; N, 5.5. C8H19BrClN
requires C, 39.28; H, 7.38; N, 5.73%]; nmax (KBr) 3150,
3070, 2020, 1404, 630 cm21; dH (D2O) 3.48 (1H, d,
J¼13.9 Hz, CH2–N), 3.39 (1H, d, J¼13.9 Hz, CH2–N),
2.19 (1H, d, J¼15.5 Hz, Me3C–CH2), 2.07 (1H, d,
J¼15.5 Hz, Me3C–CH2), 2.19, 2.07 (2H, 2d, J¼15.5 Hz,
Me3C–CH2), 1.94 (3H, s, CH3–C(Br)), 1.07 (9H, s, Me3C);
FAB/MS: 210 (2, MKþ2), 208 (2, MK), 164 (18), 128 (100),
111 (46), 57 (66), 30 (54%).
4.6.4. 2-Bromohexylamine tosylate (10e). Yield 60%,
colorless solid, mp 129–1318C (EtOH–Et2O); [Found: C,
44.1; H, 6.5; N, 4.1. C13H22BrNO3S requires C, 44.32; H,
6.30; N, 3.98%]; nmax (KBr) 3090, 2940, 1604, 1516, 1460,
1220, 1160, 1136, 1038, 1008, 820, 684, 572 cm21; dH 7.95
(3H, bs, NH3), 7.17–7.80 (4H, AA0BB0 system C6H4),
4.02–4.13 (1H, m, CHBrCH2), 3.05–3.33 (2H, m,
CH2NH3), 2.36 (3H, s, CH3C6H4), 1.53–1.73 (2H, m,
CH2CHBr), 1.11–1.42 (4H, m, CH3(CH2)2), 0.82 (3H, t,
J¼7.1 Hz, CH2); FAB/MS: 254 (9, Mþ3), 252 (10, Mþ1),
182 (93, MKþ2), 180 (100, MK), 100 (31), 30 (19 %).
4.5.9. 2-Bromo-2-phenylethylamine hydrochloride (9i).
Yield 88%, colorless plates, mp 165–1678C (dec.) (EtOH–
Et2O); [Found: C, 40.4; H, 4.7; N, 6.1. C8H11BrClN requires
C, 40.62; H, 4.69; N, 5.92%]; nmax (KBr) 2880, 2660, 1610,
1515, 1460, 930, 890, 770, 705, 690 cm21; dH (D2O) 7.43–
7.60 (5H, m, Ph), 5.35 (1H, dd, J¼9.25, 5.75 Hz, CHBr–
CH2–N), 3.80 (1H, dd, J¼13.8, 9.25 Hz, CHBr–CH2–N),
3.69 (1H, dd, J¼13.8, 5.75 Hz, CHBrCH2–N); FAB/MS:
202 (34, MKþ2), 200 (35, MK), 156 (23), 120 (100), 104
(80), 77 (45), 30 (64%).
4.6.5. 2-Bromoheptylamine tosylate (10f). Yield 60%,
colorless solid, mp 195–1968C (dec.) (EtOH–Et2O);
[Found: C, 46.1; H, 6.7; N, 3.9. C14H24BrNO3S requires
C, 45.91; H, 6.61; N, 3.82%]; nmax (KBr) 3190, 3088, 2090,
1830, 1600, 1470, 1450, 1164, 1136, 1040, 1012, 816, 0684,
572 cm21; dH 7.95 (3H, bs, NH3), 7.17–7.80 (4H, AA BB0
system C6H4), 4.02–4.13 (1H, m, CHBrCH2), 3.05–3.32
(2H, m, CH2NH3), 2.36 (3H, s, CH3C6H4), 1.53–1.73
(2H, m, CH2CHBr), 1.06–1.44 (6H, m, CH3(CH2)3),
0.83 (3H, t, J¼6.9 Hz, CH3CH2); FAB/MS: 368 (5,
Mþ3), 366 (6, Mþ1), 196 (MKþ2), 194 (100, MK), 55
(45), 30 (40%).
4.6. Deprotection of BBC adducts (9b–i) with
p-toluenesulfonic and. Preparation of 2-bromoalkyl-
amine tosylates (10b–i)
A solution of p-toluenesulfonic acid monohydrate (0.95 g,
5 mmol) in EtOH (2 mL) was added to the solution of crude
BBC adduct (9b–i) in CH2Cl2 (30 mL) and the mixture was
refluxed gently for 1 h. The solvent was evaporated in vacuo
and ether (30 mL) was added to the residue. The
precipitated tosylates (10b–i) were filtered and washed
with ether.
4.6.6. 2-Bromooctylamine tosylate (10g). Yield 58%,
colorless solid, mp 180–1818C (dec.) (EtOH–Et2O);
[Found: C, 47.1; H, 7.0; N, 3.5. C15H26BrNO3S requires
C, 47.37; H, 6.89; N, 3.68%]; nmax (KBr) 3090, 2940, 1618,
1520, 1460, 1230, 1165, 1136, 1038, 1008, 816, 684,
568 cm21; dH 7.95 (3H, bs, NH3), 7.16–7.79 (4H, AA0BB0
system, C6H4), 4.02–4.12 (1H, m, CHBr), 2.93–3.32 (2H,
m, CHBrCH2), 2.36 (3H, s, CH3C6H4), 1.11–1.53 (2H, m,
CH2CHBr), 1.18–1.39 (8H, m, CH3(CH2)4), 0.85 (3H, t,
J¼6.75 Hz, CH3CH2); FAB/MS: 382 (4, Mþ3), 380 (4,
Mþ1), 210 (93, MKþ2), 208 (100, MK), 128 (63), 69 (49),
41 (72), 30 (66%).
4.6.1. 2-Bromo-2-methylpropylamine tosylate (10b).
Yield 76%, colorless solid, mp 140–1418C (EtOH–Et2O);
[Found: C, 40.9; H, 5.7; N, 4.4. C11H18BrNO3S requires C,
40.75; H, 5.60; N, 4.32%]; nmax (KBr) 2950, 2640, 1625,
1540, 1500, 1464, 1408, 1384, 1234, 1172, 1040, 1014, 820,
680, 630, 572 cm21; dH 8.02 (3H, bs, NH3), 7.17–7.79 (4H,
AA0BB0 system, C6H4), 3.11 (2H, q, J¼5.75 Hz, CH2–
NH3), 2.36 (3H, s, CH3–C6H4), 1.72 (6H, s, Me2C); FAB/
MS: 326 (13, Mþ3), 324 (14, Mþ1) 154 (98, MKþ2), 152
(100, MK), 137 (19), 135 (19), 72 (95), 55 (46), 30 (27%).
4.6.2. 2-Bromo-2-methylbutylamine tosylate (10c). Yield
75%, colorless solid, mp 140–1438C (EtOH–Et2O);
[Found: C, 42.4; H, 6.0; N, 4.3. C12H20BrNO3S requires
C, 42.61; H, 5.96; N, 4.14%]; nmax (KBr) 3080, 2940, 1630,
1558, 1500, 1475, 1452, 1170, 1136, 1040, 1014, 822, 0684,
572 cm21; dH 8.01 (3H, bs, NH3), 7.18–7.79 (4H, AA BB0
system, C6H4), 3.09 (2H, q, J¼5.9 Hz, CH2–NH3), 2.36
(3H, s, CH3–C6H4), 1.84, 1.74 (2H, 2q, J¼7.25 Hz,
CH3CH2), 1.68 (3H, s, MeC(Br), 0.94 (3H, t, J¼7.25 Hz,
4.6.7. 2-Bromo-2,4,4-trimethylpentylamine tosylate
(10h). Yield 55%, colorless solid, mp 155–1568C (dec.)
(EtOH–Et2O); [Found: C, 47.1; H, 7.0; N, 3.5. C15H26-
BrNO3S requires C, 47.37; H, 6.89; N, 3.68%]; nmax (KBr)
3190, 3084, 1646, 1604, 1472, 1454, 1200, 1164, 1136,
1050, 1012, 820, 690, 634, 625, 572 cm21; dH 8.03 (3H,
bs, NH3), 7.17–7.81 (4H, AA0BB0 system, C6H4), 3.13–
3.20 (2H, m, CH2NH3), 2.36 (s, 3H, CH3C6H4), 1.99
(1H, d, J¼5.55 Hz, t-Bu-CH2), 1.86 (1H, d, J¼15.55 Hz,

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A. Sliwinska, A. Zwierzak / Tetrahedron 59 (2003) 5927–5934
5934
t-Bu-CH2), 1.83 (3H, s, CH3CHBr), 0.96 (9H, s, Me3C);
FAB/MS: 382 (3, Mþ3), 380 (3, Mþ1), 210 (76, MKþ2),
208 (73, MK) 128 (95), 57 (100), 41 (47), 30 (27%).
Acknowledgements
Financial support by a grant 4T09A 047 23 from the State
Committee of Scientific Researches (KBN) is gratefully
acknowledged.
4.6.8. 2-Bromo-2-phenylethylamine tosylate (10i). Yield
86%, colorless solid, mp 130–1328C (dec.) (EtOH–Et2O);
[Found: C, 48.2; H, 4.9; N, 3.9. C15H18BrNO3S requires C,
48.40; H, 4.88; N, 3.76%]; nmax (KBr) 3030, 2900, 1604,
1512, 1460, 1220, 1170, 1128, 1040, 1008, 868, 820, 760,
680, 600, 572 cm21; dH 8.04 (3H, bs, NH3), 7.14–7.78 (4H,
AA0BB0 system, C6H4, 5.15 (1H, dd, J¼8.75, 6.0 Hz,
CHBrCH2), 3.31–3.37 (2H, m, CHBrCH2), 2.34 (3H, s,
CH3C6H4); FAB/MS: 374 (8, Mþ3), 372 (8, Mþ1), 202
(85, MKþ2), 200 (91, MK), 185 (26), 183 (25), 120 (100),
104 (79), 91 (24), 30 (41%).
References
1. (a) Tanner, D. Angew. Chem. Int. Ed. Engl. 1994, 33,
599–619, and references cited therein. (b) Mc Coull, W.;
Davis, F. A. Synthesis 2000, 1347–1365. (c) Sweeney, J. B.
Chem. Soc. Rev. 2002, 247–258.
2. Zawadzki, S.; Zwierzak, A. Tetrahedron 1981, 37,
2675–2681.
4.7. Addition of BBC (3) to (E)-1-phenylpropene
followed by deprotection with HCl
3. Osowska-Pacewicka, K.; Zwierzak, A. Tetrahedron 1985, 41,
4717–4725.
4. Loev, B.; Kormendy, M. F. J. Org. Chem. 1963, 28,
3421–3426.
Addition and deprotection were carried out as described for
other hydrocarbons. Yield 70%, colorless solid, mp 161–
1658C (dec.); [Found: C, 43.0; H, 5.3; N, 5.7. C9H13BrClN
requires C, 43.14; H, 5.23; N, 5.59%]; dH 8.72 (3H, bs, NH3),
7.11–7.59(5H,m, Ph), 5.53(1H, d,J¼5.0 Hz, CHBrerythro),
5.22 (1H, d, J¼10.0 Hz, CHBr threo), 3.62–3.83, 3.88–4.10
(1H, 2m, CHCH3), 1.33, 1.54 (3H, 2d, J¼6.5 Hz, CH3CH).
5. (a) Hanack, M. Conformation Theory; Academic: New York,
1965; p 333. See also: Cahn, R. S.; Ingold, C. K.; Prelog, V.
Experientia 1956, 12, 81–100.
6. Benedetti, F.; Norbedo, S. Tetrahedron Lett. 2000, 41,
10071–10074.
7. Mixer, R. Y.; Heck, R. F.; Winstein, S.; Young, W. Y. J. Am.
Chem. Soc. 1953, 75, 4094–4096.
4.8. Addition of BBC (3) to (Z)-1-phenylpropene
followed by deprotection with HCl
8. Walling, C.; Heaton, L. D.; Tanner, D. D. J. Am. Chem. Soc.
1965, 87, 1715–1721.
9. Poutsma, M. L. J. Am. Chem. Soc. 1965, 87, 2161–2171, pp
2172–2183.
Addition and deprotection were carried out as described for
other hydrocarbons. Yield 57%, colorless solid, mp 168–
1718C (dec.); [Found: C, 43.2; H, 5.4; N, 5.8. C9H13BrClN
requires C, 43.14; H, 5.23; N, 5.59%]; dH 8.77 (3H, bs, NH3),
7.26–7.55 (5H, m, Ph), 5.48 (1H, J¼5.25 Hz, CHBr erythro),
5.19 (1H, d, J¼10.25 Hz, CHBr threo), 3.67–3.81, 3.91–4.08
(1H, 2m, CHCH3), 1.33, 1.55 (3H, 2d, J¼6.5 Hz, CH3CH).
10. Wessig, P.; Schwarz, J. Synlett 1997, 893–894, and references
cited therein.
´
11. Mieczkowski, J. B. Bull. Acad. Polon. Sci., Ser. Sci. Chim.
1986, 34, 109–113.