Ionic addition of t-butyl N,N-dibromocarbamate (BBC) to alkenes and cycloalkenes

Article abstract of DOI:10.1016/j.tetlet.2003.10.040

The addition of t-butyl N,N-dibromocarbamate (BBC) to alkenes and cycloalkenes in the presence of BF₃·Et₂O proceeds smoothly at -20°C in CH₂Cl₂ affording upon reduction with aqueous Na₂SO₃ the corresponding β-bromo-N-Boc- amines. Immediate deprotection of these adducts with gaseous HCl yields β-bromoamine hydrochlorides in moderate yields. The regioselectivity typical for Markovnikov addition was observed for styrene. Stereospecific anti-addition of BBC to cyclohexene and (E)-hex-3-ene, as proven by ¹H NMR evidence, is compatible with an ionic addition pathway and can be rationalized by assuming the intermediate complex formation between BBC and BF₃.

Full text of DOI:10.1016/j.tetlet.2003.10.040

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 9323–9325
Ionic addition of t-butyl N,N-dibromocarbamate (BBC) to
alkenes and cycloalkenes
´
Anna Sliwin´ska and Andrzej Zwierzak*
:
Institute of Organic Chemistry, Technical University (Politechnika), Zeromskiego 116, 90-924 Ło´dz; , Poland
Received 1 August 2003; revised 30 September 2003; accepted 10 October 2003
Abstract—The addition of t-butyl N,N-dibromocarbamate (BBC) to alkenes and cycloalkenes in the presence of BF3·Et2O
proceeds smoothly at −20°C in CH2Cl2 affording upon reduction with aqueous Na2SO3 the corresponding b-bromo-N-Boc-
amines. Immediate deprotection of these adducts with gaseous HCl yields b-bromoamine hydrochlorides in moderate yields. The
regioselectivity typical for Markovnikov addition was observed for styrene. Stereospecific anti-addition of BBC to cyclohexene
1
and (E)-hex-3-ene, as proven by H NMR evidence, is compatible with an ionic addition pathway and can be rationalized by
assuming the intermediate complex formation between BBC and BF3.
© 2003 Elsevier Ltd. All rights reserved.
While free-radical addition of various N,N-
dihaloamides to carbonꢀcarbon double bonds has been
extensively studied,1 the available information regard-
ing ionic reactions of such systems with unsaturated
compounds still remains scarce.2
stoichiometric amount of BF3·Et2O using the pre-
formed BBC-BF3 complex (vide infra) as a source of
electropositive bromine. The reaction was carried out in
CH2Cl2 by dropwise addition of the hydrocarbon to an
equimolar mixture of BBC 1 and BF3·Et2O at −20°C.
The reaction was rapid and was virtually complete
within 1 h. Upon reduction with 12% aqueous Na2SO3
at 5–10°C the initially formed N-bromo adduct was
We have recently proved the efficiency of t-butyl N,N-
dibromocarbamate (BBC) 1 for free-radical regioselec-
tive aminobromination of terminal alkenes.3 Homolytic
addition of BBC 1 to non-terminal alkenes and
cycloalkenes occurs, however, sluggishly leading
inevitably to complex and often intractable mixtures of
compounds. This observation prompted us to investi-
gate the possibility of heterolytic addition of BBC to
double bonds with the hope of extending the prepara-
tive applicability of this reagent.
reduced into N-Boc-2-bromo-1-phenylethylamine
3
(Scheme 1). The Markovnikov orientation of this com-
pound was confirmed by comparing its mp and spectral
data with those of the regioisomer prepared by free-
radical addition of BBC 1 to styrene.4 The addition
procedure elaborated for styrene could be then
extended to other unsaturated hydrocarbons.5
Cycloalkenes 5a–c added BBC 1 easily and cleanly
affording the corresponding N-Boc-b-bromocycloalkyl-
amines 6a–c in moderate yields (Scheme 2).6 In contrast
to free-radical additions the reactions of BBC-BF3
It was found that clean heterolytic addition of BBC 1
to styrene 2 could be accomplished in the presence of a
Scheme 1.
Keywords: alkenes; amines; cycloalkenes; ionic addition.
* Corresponding author. Tel.: +48-42-6313146; fax: +48-42-6365540.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.10.040

´
A. Sliwin´ska, A. Zwierzak / Tetrahedron Letters 44 (2003) 9323–9325
9324
Scheme 2.
anti-addition of BBC-BF3 to cyclohexene 5b could be
corroborated by detailed analysis of the 1H NMR
spectra of 6b and 7b.9 The configurations and confor-
mations of these compounds follow from the splitting
patterns and the large vicinal methine proton coupling
constants (J=10.1 and 11.1 Hz, respectively) which are
typical for the axial arrangement.
The ionic mechanism of BBC-BF3 addition can be
rationalized by assuming formation of the BBC-BF3
intermediate complex 11a–c (Scheme 4) leading to sub-
sequent ionization of the BBC molecule. It was found
that addition of an equimolar amount of BF3·Et2O to
the solution of BBC in CH2Cl2 changes the IR spec-
trum of the reagent. The CꢁO absorption band at 1724
cm−1 is shifted to 1655 and 1630 cm−1 suggesting a
considerably diminished bond order of the carbonyl
group consistent with the two contributing structures
11b and 11c.
Scheme 3.
with terminal alkenes, such as pent-1-ene and hex-1-ene
were not regioselective affording ca. 1:1 mixtures of
both regioisomers as determined by 1H NMR. All
N-Boc-adducts 3, 6a–c, and 9 could be immediately
deprotected without purification to the corresponding
b-bromoamine hydrochlorides 4, 7a–c, and 10 by
means of gaseous HCl in CH2Cl2 at 0°C (1 h) and then
at room temperature (24 h).3
In conclusion we have demonstrated the possibilities of
heterolytic BBC 1 addition to alkenes and cycloalkenes
as a convenient route to some N-Boc-b-bromoamines
and b-bromoamine hydrochlorides (Table 1).
(E)-Hex-3-ene 8 was used as a model compound for
studying the stereochemistry of the BBC-BF3 addition.
Pure erythro diastereoisomer
9 was obtained by
stereospecific anti-addition under heterolytic conditions
(Scheme 3).7 The stereochemical assignment could be
1
arrived at by H NMR after deprotection of 9 into the
Acknowledgements
b-bromoamine hydrochloride 10. The synclinal
arrangement of vicinal methine protons in the preferred
conformation of the erythro-isomer 108 is fully compat-
ible with the low value (J=2.9 Hz) of the respective
coupling constant according to Karplus equation. The
Financial support by a grant 4 T09 A 04723 from the
State Committee for Scientific Research (KBN) is
gratefully acknowledged.
Scheme 4.

´
A. Sliwin´ska, A. Zwierzak / Tetrahedron Letters 44 (2003) 9323–9325
9325
Table 1. Preparation of b-bromo-N-Boc-amines (3, 6a–c, 9)
and b-bromoamine hydrochlorides (4, 7a–c, 10)a
CH2Cl2 (6 mL) was added over 15 min at −20°C and
stirring was continued at this temperature for 1 h. The
resulting pale yellow solution was warmed to 5–10°C and
a 12% aqueous solution of Na2SO3 (10 mL) was added
slowly at this temperature. Dichloromethane (20 mL) was
then added, the organic layer was separated and washed
with water (3×10 mL). After drying (MgSO4) the solvent
was removed under reduced pressure and the residue was
purified by silica gel chromatography using CHCl3 as
eluent to give the pure isolated products 3, 6, and 9.
Compounds 3 and 6 were recrystallized from hexane.
6. Selected data for compounds 6a–c. Compounds 6a: 1H
NMR (250 MHz, CDCl3): 4.58 (1H, bs, CH-NH), 4.11–
4.17 (2H, m, CHNH and CHBr); 2.17–2.36 (2H, m,
CH2), 1.67–2.11 (4H, m, CH2), 1.46 (9H, s, Me3C).
Compound no
Yield (%)
Mp (°C)
Lit.10 mp (°C)
e
e
e
e
e
3
70
63
55
48
106–108c
73–74c
6a
6b
6c
9
98–99c
79–81c
–
63
4
65b
65b
60b
50b
57b
178–180d
192–194d
198–200d
164–166d
178–180d
176–178
182–184
187–189
152–154
157–159
7a
7b
7c
10
a All new compounds were fully characterized by MS, IR, and 1H
NMR spectroscopy.
1
Compound 6b: H NMR (250 MHz, CDCl3): 4.63 (1H,
bs, NH), 3.87 (1H, dt, J=10.1, 4.25 Hz, CHBr), 3.61
(1H, ddt, J=10.1, 8.5, 3.75 Hz, CH-NH), 2.31–2.41 (2H,
m, CH2), 2.17–2.24 (2H, m, CH2), 1.81–1.97 (2H, m,
CH2), 1.65–1.76 (2H, m, CH2), 1.46 (9H, s, Me3C).
MS/CI: 280 (60, M+3), 278 (63, M+1), 224 (95), 222
b Overall yield after immediate deprotection of the crude adduct.
c Crystallized from hexane.
d Crystallized from ethanol–ether.
e Not reported previously.
1
(100). Compound 6c: H NMR (250 MHz, CDCl3): 4.76
(bs, 1H, NH), 4.12 (1H, ddd, J=8.5, 8.25, 4.0 Hz,
CHBr), 3.78–3.88 (1H, m, CHNH), 1.99–2.42 (3H, m,
CH2), 1.45–1.82 (7H, m, CH2), 1.45 (9H, s, Me3C).
7. Selected data for compound 9: 1H NMR (250 MHz,
CDCl3): 4.68 (1H, d, J=9.0 Hz, NH), 4.14 (1H, dt,
J=7.1, 3.0 Hz, CHBr), 3.50–3.60 (1H, m, CHNH), 1.85
(2H, qt, J=7.1 Hz, CH2-CHBr), 1.60–1.77 (2H, m, CH2-
CHNH), 1.45 (9H, s, Me3C), 1.07 (3H, t, J=7.1 Hz,
CH3-CH2-CHBr), 0.97 (3H, t, J=7.3 Hz, CH3-CH2-
CHNH). MS/CI: 226 (1.1, M+4-C4H9), 224 (1.6, M+2-
C4H9), 182 (92, M+4-Boc), 180 (100, M+2-Boc).
8. Selected data for compound 10: IR (KBr) wmax 3460,
2980, 2950, 1592, 1520, 1465, 1390, 1312, 1200, 1150, 792,
630, 620 cm−1. 1H NMR (250 MHz, D2O): 4.32 (1H, ddd,
J=9.6, 4.5, 2.9 Hz, CH-Br), 3.48 (1H, ddd, J=9.25, 4.5,
2.9 Hz, CH-NH3), 1.65–1.98 (4H, m, 2×CH2), 1.06 (3H,
t, J=6.9 Hz, CH3), 1.03 (3H, t, J=7.1 Hz, CH3).
9. Selected data for compound 7b: 1H NMR (250 MHz,
D2O), 4.10 (1H, dt, J=11.1, 4.4 Hz, CH-Br), 3.41 (1H,
dt, J=11.1, 4.2 Hz, CH-NH3), 2.39–2.46 (1H, m, CH2),
2.10–2.21 (1H, m, CH2), 1.66–1.97 (3H, m, CH2), 1.26–
1.59 (3H, m, CH2).
References
1. Neale, R. S. Synthesis 1971, 1–15 and references cited
therein.
2. Zwierzak, A.; Osowska, K. Angew. Chem., Int. Ed. Engl.
1976, 15, 302–303.
3. (a) Klepacz, A.; Zwierzak, A. Tetrahedron Lett. 2001, 42,
´
4539–4540; (b) Sliwin´ska, A.; Zwierzak, A. Tetrahedron
2003, 59, 5927–5934.
4. Selected data for the compound 3: IR (KBr), wmax 3400,
2990, 1680, 1512, 1392, 1368, 1280, 1248, 1168, 1048,
1
1024, 700, 660, 640 cm−1. H NMR (250 MHz, CDCl3):
7.28–7.41 (5H, m, Ph), 5.13 (1H, bs, NH), 5.01 (1H, bs,
CH-NH), 3.63–3.75 (2H, m, CH2Br), 1.44 (9H, s, Me3C).
MS/CI: 302 (49, M+3), 300 (51, M+1), 246 (98), 244
(100). [Found: C, 52.0; H, 6.1; N, 4.7. C13H18BrNO2
requires C, 52.01; H, 6.04; N, 4.67%].
5. General procedure for the preparation of compounds 3,
6, and 9: To
a solution of crude t-butyl N,N-
dibromocarbamate3 (BBC, 1, 2.75 g, 10 mmol) in CH2Cl2
(28 mL), BF3·Et2O (1.40 g, 10 mmol) dissolved in CH2Cl2
(6 mL) was added with stirring and cooling at −20°C.
After 15 min the solution of hydrocarbon (10 mmol) in
10. Osowska-Pacewicka, K.; Zwierzak, A. Tetrahedron 1985,
41, 4717–4725.