Regioselective copper(II)-mediated bromoamination of unfunctionalized olefins: An efficient route to N-heterocyclic compounds

Article abstract of DOI:10.1002/adsc.201301125

Bromoamination of unfunctionalized olefins was realized under mild conditions using copper(II) bromide (CuBr₂) as both reaction promoter and bromine source. The reactions could be carried out under open air at ambient temperature, and both N-alkylated and N-tosylated substrates could be converted to the corresponding N-heterocyclic compounds in high regioselectivity and good isolated yields. A variety of biologically important structures could be obtained via subsequent nucleophilic substitution reactions.

Full text of DOI:10.1002/adsc.201301125

Supporting Information
©
Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2013

Supporting Information for:
Highly Regioselective Copper(II)-mediated Bromoamination of Unfunctionalized
Olefins: An Efficient Route to N-Heterocyclic Compounds
Gong-Qing Liu, Zhen-Ying Ding, Li Zhang, Ting-Ting Li, Lin Li, Lili Duan and Yue-Ming Li*
College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, 94 Weijin Road,
Tianjin 300071, People’s Republic of China. Fax: 86 22 2350 7760; E-mail: ymli@nankai.edu.cn
Table of Contents
1. General information...................................................................................................1
2. Derivatization of Chloramination Product.................................................................1
3. Investigation of Solvent Effect ..................................................................................2
4. Synthesis and Characterization of Aminoalkene Substrates......................................2
5. General Procedures for Bromoamination ................................................................11
6. Derivatization of Bromoamination Product.............................................................20
7. Copies of NMR Spectra...........................................................................................24
8. X-ray Crystal Structure and Data of 5b ...................................................................95
9. References..............................................................................................................101

1. General information
Reactions were carried out using commercially available reagents in oven-dried
1
13
apparatus. H and C NMR spectra were recorded on a Bruker DRX 400
spectrometer at 298 K using deuterated chloroform as solvent and TMS as the internal
reference. Column chromatography was performed employing 200-300 mesh silica
gel unless otherwise noted. Thin layer chromatography (TLC) was performed on
silica gel GF . High resolution mass spectral analyses (HRMS) analyses were
2
54
carried out with Varian FTICR-MS 7.0T. Unless otherwise indicated, starting
materials and reagents used in reactions were purchased from J&K Chemicals
(
Beijing) or Aladdin Reagents (Shanghai) and were used as received without further
purification.
2
. Derivatization of Chloramination Product
Table 1. Derivatization of N-benzyl-2-chloromethyl-4,4-diphenylpyrrolidine.
a
a
Entry
Nucleophile
BnNH
Sa'
31
43
36
45
40
Sa''
45
1
2
3
4
5
2
KOAc
NaN3
32
32
NaCN
PhSNa
40
34
a: Isolated Yield.
Table 2. Derivatization of N-benzyl-3-chloro-5,5-diphenylpiperidine.
a
a
Entry
Nucleophile
BnNH
Sb'
10
14
13
6
Sb''
1
2
61
68
78
83
66
2
KOAc
NaN3
3
4
NaCN
PhSNa
5
21
a: Isolated Yield.
1

3
. Investigation of Solvent Effect
Table 3. Optimization of reaction conditions.
a
Entry
solvent
Hexane
Conversion
52
1
2
3
4
5
6
7
8
9
CH
3
CN
>99
56
Acetone
CHCl
THF
3
60
79
Benzene
83
Toluene
80
Dioxane
87
DCE
88
1
0
1
DMSO
65
1
DMF
86
b
1
2
3
CH CN
>99
>99
>99
50
3
3
3
3
3
3
c
1
1
1
CH CN
d
4
CH CN
e
5
CH CN
f
1
6
CH CN
31%
g
1
7
CH CN
Unresolved complex
mixture
a: Determined by crude NMR analysis. b: in the presence of 1 equiv. of K . c: in the presence
2
CO
3
of 1 equiv. of Cs CO . d: 50 mol% CuBr , 5 d, open air. e: 50 mol% CuBr , 5 d, under argon
2
3
2
2
atmosphere. f: isolated yield, in the presence of
N-benzyl-5-penten-1-amine was used as substrate.
1
equiv. of TEMPO. g:
1
4
. Synthesis and Characterization of Aminoalkene Substrates
A solution of diphenylacetonitrile (9.65 g, 50 mmol) in DMF (20 mL) was added
slowly to a suspension of NaH (1.32 g, 55 mmol) in DMF (50 mL) and the resulting
2

mixture was stirred at room temperature for 1 hour. The resulting bright yellow
suspension was cooled to 0°C, treated with allyl bromide (6.66 g, 55 mmol), warmed
to room temperature and stirred at room temperature for 12 hours. The resulting
solution was poured into ice/water (200 mL) and was extracted with CH Cl (3100
2
2
mL). The combined organic layer was washed with water (250 mL), dried with
MgSO , and concentrated to give 2,2-diphenyl-4-pentenenitrile (S1) (10.83 g, 93%),
4
which was used in the subsequent step without further purification.
To a suspension of LiAlH (1.52 g, 40 mmol) in THF (130 mL) was added S1 (2.33 g,
4
1
0 mmol) at 0°C. The mixture was slowly warmed to room temperature and stirred
overnight. The resulting suspension was cooled to 0°C and quenched by slow addition
of 6 M NaOH (50 mL). The resulting mixture was extracted with CH Cl (4100 mL)
and the combined ether extracts were dried (MgSO ) and concentrated to give
2
2
4
2
,2-diphenyl-diphenyl-4-pentenylamine (S2) (2.01g, 85%) as a pale yellow, viscous
oil.
A solution of S2 (1.19 g, 5 mmol) and benzaldehyde (0.54 g, 5.1mmol) in MeOH (20
mL) was stirred at room temperature for 5 h, then treated with NaBH (0.29g, 7.5
4
mmol) and the mixture was stirred overnight. The resulting mixture was treated with
water (50 mL), 1 M NaOH (20 mL) and then was extracted with CH Cl (3100 mL).
2 2
The combined organic layer was dried (MgSO ) and concentrated. The resulting oily
4
residue was chromatographed to give 4a (1.32 g, 86%) as a viscous oil.
The N-substituted 4-penten-1-amines 4b-4g, were synthesized via reductive amination
of S2 with the corresponding aldehydes or ketones via procedures similar to that used
to synthesize 4a.
1
2
1
,2-Diphenylpent-4-enenitrile (S1) H NMR (400 MHz, CDCl
3
) δ = 7.46-7.19 (m,
1
3
0H), 5.70 (ddt, J=17.1, 10.2, 7.0, 1H), 5.31-5.05 (m, 2H), 3.12 (d, J=7.0, 2H). C
) δ = 139.81, 131.84, 128.90, 127.99, 127.10, 121.94, 120.43,
1.85, 43.98. Spectral data was consistent with the known aminoalkene.
NMR (100 MHz, CDCl
5
3
1
1
2
1
2
5
,2-Diphenylpent-4-en-1-amine (S2) H NMR (300 MHz, CDCl
3
) δ = 7.37-6.91 (m,
0H), 5.51-5.27 (m, 1H), 5.17-4.83 (m, 2H), 3.31 (s, 2H), 2.92 (d, J=7.0, 2H), 0.77 (s,
H). C NMR (75 MHz, CDCl ) δ = 146.33, 134.69, 128.24, 128.11, 126.10, 117.72,
3
1.50, 48.62, 41.17. Spectral data was consistent with the known aminoalkene.
1
3
1
1
N-Benzyl-2,2-diphenylpent-4-en-1-amine (4a) H NMR (300 MHz, CDCl
3
) δ =
7
.21-7.07 (m, 15H), 5.40-5.12 (m, 1H), 4.86 (m, 2H), 3.64 (s, 2H), 3.12 (s, 2H), 2.96
1
3
(
d, J=7.0, 2H), 0.91(brs, 1H). C NMR (75 MHz, CDCl
3
) δ = 147.05, 140.92, 135.07,
1
4
28.40, 128.27, 128.17, 128.12, 126.91, 126.18, 117.87, 55.45, 54.37, 50.34,
1.81.Spectral data was consistent with the known aminoalkene.
1
3

1
N-(4-Methylbenzyl)-2,2-diphenylpent-4-en-1-amine (4b) H NMR (400 MHz,
CDCl ) δ = 7.26-7.05 (m, 14H), 5.39-5.23 (m, 1H), 5.03-4.83 (m, 2H), 3.66 (s, 2H),
3
1
3
3
.19 (s, 2H), 3.03 (d, J=7.1, 2H), 2.30 (s, 3H), 0.81 (brs, 1H). C NMR (100 MHz,
3
CDCl ) δ = 146.94, 137.76, 136.24, 135.00, 128.94, 128.15, 128.00, 127.91, 126.00,
+
1
18.23, 55.38, 53.99, 50.25, 41.72, 21.14. HRMS–ESI (m/z): [M+H] calcd for
25
C H27N: 342.2222; found: 342.2220.
1
N-(4-Methoxybenzyl)-2,2-diphenylpent-4-en-1-amine (4c) H NMR (400 MHz,
CDCl ) δ = 7.29-7.07 (m, 12H), 6.80 (d, J=7.6, 2H), 5.33 (m, 1H), 4.93 (m, 2H), 3.77
3
1
3
(
s, 3H), 3.64 (s, 2H), 3.18 (s, 2H), 3.02 (d, J=7.0, 2H), 0.98 (brs, 1H). C NMR (100
MHz, CDCl ) δ =158.58, 146.82, 134.95, 132.78, 129.08, 128.11, 127.97, 125.93,
3
1
17.70, 113.63, 55.28, 55.24, 53.61, 50.19, 41.69.Spectral data was consistent with
2
the known aminoalkene.
1
N-(4-Fluorobenzyl)-2,2-diphenylpent-4-en-1-amine (4d) H NMR (400 MHz,
CDCl ) δ = 7.35-7.20 (m, 12H), 7.01 (t, J=8.4, 2H), 5.50-5.32 (m, 1H), 5.00 (m, 2H),
3
1
3
3
.73 (s, 2H), 3.24 (s, 2H), 3.09 (d, J=7.0, 2H), 0.95 (brs, 1H). C NMR (100 MHz,
3
CDCl ) δ =163.14, 160.73, 146.84, 134.89, 129.50, 129.42, 128.11, 128.04, 126.07,
1
9
1
-
3
17.67, 115.09, 114.88, 55.26, 53.47, 50.20, 41.68. F NMR (376 MHz, CDCl ) δ=
2
116.20. Spectral data was consistent with the known aminoalkene.
1
N-(4-Nitrobenzyl)-2,2-diphenylpent-4-en-1-amine (4e) H NMR (400 MHz, CDCl
3
)
δ = 8.16 (d, J = 8.7 Hz, 2H), 7.40 (d, J = 8.7 Hz, 2H), 7.30 (d, J = 7.6 Hz, 4H), 7.24 (d,
J = 7.2 Hz, 2H), 7.20 (d, J = 7.4 Hz, 4H), 5.44-5.23 (m, 1H), 5.00 (dd, J = 37.2, 13.6
1
3
Hz, 2H), 3.84 (s, 2H), 3.22 (s, 2H), 3.09 (d, J = 7.0 Hz, 2H). 0.96(brs,1H). C NMR
100 MHz, CDCl ) δ = 148.57, 146.55, 134.73, 128.50, 128.10, 128.01, 126.57,
26.19, 123.49, 117.77, 55.38, 53.42, 50.14, 41.55. Spectral data was consistent with
(
3
1
1
the known aminoalkene.
1
N-Isobutyl-2,2-diphenylpent-4-en-1-amine(4f) H NMR (300 MHz, CDCl
3
) δ =
.43-7.17 (m, 10H), 5.44 (dt, J = 17.1, 8.5 Hz, 1H), 5.05 (dd, J = 37.5, 13.3 Hz, 2H),
.24 (s, 2H), 3.09 (d, J = 7.0 Hz, 2H), 2.39 (d, J = 6.8 Hz, 2H), 1.79-1.63 (m, 1H),
7
3
0
1
1
3
.83 (d, J = 6.6 Hz, 6H), 0.47 (s, 1H). C NMR (100 MHz, CDCl
28.13, 127.97, 125.96, 117.58, 58.52, 55.96, 50.21, 41.68, 27.85, 20.56.Spectral data
3
) δ = 147.06, 135.14,
2
was consistent with the known aminoalkene.
4

1
N-Isopropyl-2,2-diphenylpent-4-en-1-amine (4g) H NMR (300 MHz, CDCl
3
) δ =
7
2
.19-7.03 (m, 10H), 5.28 (ddt, J=17.1, 10.0, 7.1, 1H), 4.99-4.70 (m, 2H), 3.11 (s, 2H),
1
3
.91 (d, J=7.1, 2H), 2.54 (hept, J=6.2, 1H), 0.84 (d, J=6.3, 6H), 0.26 (brs, 1H). C
) δ = 147.07, 135.02, 128.11, 127.93, 125.90, 117.55, 53.64,
9.97, 49.26, 41.61, 23.13. Spectral data was consistent with the known
NMR (75 MHz, CDCl
4
aminoalkene.
3
3
N-Benzyl-2,2-dimethylpent-4-en-1-amine (4h) Isobutyronitrile (50 mmol) was
added to a solution of LDA [generated in situ from n-BuLi and diisopropylamine
(12.4 g,123 mmol) in THF (300 mL)] at -78°C and the mixture was stirred at this
temperature for 1h. To the resulting solution was added allyl bromide (21.5 mL, 248
mmol). The solution was warmed to room temperature and was stirred overnight.
CH Cl (75 mL) was added and the resulting biphasic mixture was washed with water
2
2
(
3100 mL), dried (MgSO ), and carefully concentrated, due to the volatility of the
4
cyanide,
to
give
2,2-dimethyl-4-pentenenitrile.
Conversion
of
2,
2
-dimethyl-4-pentenenitrile to 4h was accomplished in a manner similar to that
1
employed for the conversion of S2 to 4a-4g. H NMR (400 MHz, CDCl
3
) δ =
7
2
.58-7.13 (m, 5H), 5.99-5.74 (m, 1H), 5.11 (d, J = 13.6 Hz, 2H), 3.88 (s, 2H), 2.47 (s,
1
3
H), 2.13 (d, J = 7.4 Hz, 2H), 1.29 (s, 1H), 1.00 (d, J = 1.0 Hz, 6H). C NMR (100
) δ = 141.10, 135.68, 128.36, 128.05, 126.83, 116.86, 59.76, 54.80, 44.73,
MHz, CDCl
3
3
1
4.46, 25.64. Spectral data was consistent with the known aminoalkene.
1
-(1-Allylcyclohexyl)-N-benzylmethanamine (4i) Compound 4i was synthesized
employing procedure similar to that used to synthesize 4h starting from
1
cyclohexanenitrile. H NMR (400 MHz, CDCl
3
) δ =7.37-6.88 (m, 5H), 5.76 (ddd, J =
1
7.6, 10.1, 5.1 Hz, 1H), 5.08-4.87 (m, 2H), 3.76 (s, 2H), 2.41 (s, 2H), 2.11 (d, J = 7.5
1
3
Hz, 2H), 1.44-1.20 (m, 10H), 0.91 (brs, 1H). C NMR (100 MHz, CDCl
3
) δ =141.18,
1
2
35.43, 128.33, 128.10, 126.82, 116.74, 55.96, 54.76, 40.79, 36.77, 34.15, 26.57,
1.73. Spectral data was consistent with the known aminoalkene.
1
N-Benzylpent-4-en-1-amine (4j) To a solution of benzylamine (5 mmol) and
-bromo-1-pentene (1 mmol) in ethanol (30 mL) was added NaI (0.1 mmol,).The
5
mixture was stirred overnight at 75 °C and the solvent was removed in vacuo. The
resulting oily residue was chromatographed (Petroleum ether : Ethyl acetate= 5:1) to
1
give 4j (0.09g, 53%) as a clear oil. H NMR (400 MHz, CDCl
3
) δ = 7.21-7.13 (m, 5H),
5
2
.70 (m, 1H), 4.98-4.80 (m, 2H), 3.67 (s, 2H), 2.53 (t, J=7.2, 2H), 2.02 (brs, 1H),
.01-1.95 (m, 2H), 1.58-1.43 (m, 2H). C NMR (100 MHz, CDCl ) δ = 140.24,
3
1
3
5

1
38.44, 128.41, 128.19, 126.97, 114.71, 53.93, 48.80, 31.56, 29.15. Spectral data was
3
consistent with the known aminoalkene.
4
2
,2-diallyl-N-benzylpent-4-en-1-amine (4k) A flask was charged with acetonitrile
(
(
30 mmol) and THF (50 mL). This solution was cooled to -78 °C. A solution of LDA
32 mmol) was added slowly to the acetonitrile solution. After 30 minutes of stirring
at -78 °C, allyl bromide (32mmol) was added. The reaction mixture was warmed to
room temperature with stirring for 1hour before being cooled to -78 °C again. Another
equivalent of LDA solution was added, followed by 30 minutes of stirring, followed
by the addition of another equivalent of allyl bromide. The reaction was again
warmed to room temperature with stirring for 1 hour before being cooled to -78 °C.
The third LDA solution was added, followed by 30 minutes of stirring, followed by
the addition of a third equivalent of allyl bromide. Then the reaction was allowed to
warm to room temperature with stirring overnight. CH Cl (75 mL) was added and the
2
2
resulting biphasic mixture was washed with water (3100 mL), dried (MgSO
concentrated to give 2,2-diallylpent-4-enenitrile. Conversion
4
), and
of
2
,2-diallylpent-4-enenitrile to 4k was accomplished in a manner similar to that
1
employed for the conversion of S2 to 4a-4g. H NMR (400 MHz, CDCl
3
) δ = 7.44 –
6
2
1
.93 (m, 5H), 6.06 – 5.52 (m, 3H), 4.96 (dd, J = 7.6, 6.9 Hz, 6H), 3.65 (s, 2H), 2.30 (s,
13
H), 1.97 (d, J = 7.5 Hz, 6H), 1.11 (brs, 1H). C NMR (100 MHz, CDCl
3
) δ = 141.05,
34.82, 128.31, 128.08, 126.82, 117.42, 54.78, 54.70, 40.16, 39.81. HRMS–ESI (m/z):
+
[M+H] calcd for C18H25N, 256.2065; found: 256.2061.
Compounds 6a-6g was synthesized via procedures similar to that used to synthesize
a-4i starting from 4-bromo-1-butene.
4
1
N-benzyl-2,2-diphenylhex-5-en-1-amine (6a) H NMR (400 MHz, CDCl
.09 (m, 15H), 5.75 (tt, J = 16.5, 6.4 Hz, 1H), 4.97 – 4.83 (m, 2H), 3.68 (s, 2H), 3.18
s, 2H), 2.32 (dd, J = 9.9, 6.1 Hz, 2H), 1.64 (dd, J = 15.5 6.7 Hz, 2H), 1.64 (d, J = 5.2
3
) δ =7.34 –
7
(
1
3
Hz, 2H), 0.84 (brs, 1H). C NMR (100 MHz, CDCl
3
) δ = 147.27, 139.32, 129.35,
1
2
28.40, 128.21, 128.16, 128.04, 127.88, 126.12, 114.31, 55.28, 50.40, 42.70, 36.42,
8.83.Spectral data was consistent with the known aminoalkene.
5
1
N-(4-methylbenzyl)-2,2-diphenylhex-5-en-1-amine (6b) H NMR (400 MHz,
CDCl
3
) δ = 7.34 – 7.03 (m, 14H), 5.76 (ddt, J = 16.8, 10.1, 6.5 Hz, 1H), 5.21 – 4.58
(
m, 2H), 3.89 – 3.37 (m, 2H), 3.19 (s, 2H), 2.52 – 2.12 (m, 5H), 1.66 (dd, J = 15.4, 7.1
1
3
Hz, 2H), 1.27 (s, 1H). C NMR (100 MHz, CDCl
3
) δ = 147.04, 139.18, 136.29,
128.92, 128.06, 127.97, 127.95, 127.84, 125.93, 114.04, 55.15, 53.75, 50.27, 36.33,
6

+
2
8.65, 21.07. HRMS–ESI (m/z): [M+H] calcd for C26
H29N, 356.2378; found:
3
56.2375.
1
N-(4-methoxybenzyl)-2,2-diphenylhex-5-en-1-amine (6c) H NMR (400 MHz,
CDCl
3
) δ = 7.27 – 7.21 (m, 4H), 7.20 – 7.07 (m, 8H), 6.81 (d, J = 8.6 Hz, 2H), 5.86 –
5
2
.61 (m, 1H), 4.91 (dd, J = 23.7, 6.2 Hz, 2H), 3.77 (s, 3H), 3.65 (s, 2H), 3.18 (s, 2H),
.37 – 2.25 (m, 2H), 1.72 – 1.60 (m, 2H), 1.31 (s, 1H). C NMR (100 MHz, CDCl3)
1
3
δ = 147.08, 139.19, 129.01, 128.48, 128.05, 127.96, 126.55, 125.91, 114.04, 113.62,
+
5
5.25, 55.08, 53.42, 50.25, 36.32, 28.63. HRMS–ESI (m/z): [M+H] calcd for
26
C H29NO, 372.2327; found: 372.2318.
1
N-(4-fluorobenzyl)-2,2-diphenylhex-5-en-1-amine (6d) H NMR (400 MHz, CDCl
3
)
δ = 7.27 – 7.00 (m, 12H), 6.85 (t, J = 8.6 Hz, 2H), 5.66 (tt, J = 10.5, 6.5 Hz, 1H), 5.10
–
=
4.50 (m, 2H), 3.57 (s, 2H), 3.08 (s, 2H), 2.21 (dd, J = 22.0, 13.7 Hz, 2H), 1.55 (d, J
7.8 Hz, 2H), 0.82 (brs, 1H). C NMR (100 MHz, CDCl ) δ =161.95, 159.53, 145.95,
3
1
3
1
38.03, 135.29, 135.26, 128.32, 128.25, 126.96, 126.94, 124.92, 114.01, 113.80,
19
3
113.06, 54.01, 52.18, 49.17, 35.16, 27.56. F NMR (376 MHz, CDCl ) δ =
+
-116.33.HRMS–ESI (m/z): [M+H] calcd for C25
H26FN, 360.2128; found: 360.2121.
1
N-(4-chlorobenzyl)-2,2-diphenylhex-5-en-1-amine (6e) H NMR (400 MHz, CDCl
3
)
δ = 7.37 – 6.90 (m, 14H), 5.66 (ddt, J = 13.2, 10.2, 6.4 Hz, 1H), 4.81 (dd, J = 18.2, 9.1
Hz, 2H), 3.57 (s, 2H), 3.07 (s, 2H), 2.22 (dd, J = 10.0, 6.4 Hz, 2H), 1.55 (d, J = 5.3 Hz,
1
3
2
H), 0.80 (brs, 1H). C NMR (100 MHz, CDCl
3
) δ =145.90, 138.14, 138.00, 131.30,
1
28.15, 127.27, 126.95, 124.94, 113.09, 54.05, 52.20, 49.18, 35.14, 27.57. HRMS–
+
ESI (m/z): [M+H] calcd for C25H26ClN, 376.1832; found: 376.1828.
N-benzyl-2,2-dimethylhex-5-en-1-amine (6f). Compound 6f was synthesized from
isobutyronitrile and 4-bromobut-1-ene employing a procedure similar to that used to
1
synthesize 4h
.
H NMR (400 MHz, CDCl
3
) δ = 7.39 – 7.05 (m, 5H), 5.81 (ddt, J =
1
2
6.8, 10.1, 6.6 Hz, 1H), 4.94 (dd, J = 23.2, 5.9 Hz, 2H), 3.79 (s, 2H), 2.36 (s, 2H),
1
3
.01 – 1.92 (m, 2H), 1.37 – 1.31 (m, 2H), 1.15 (brs, 1H), 0.89 (s, 6H). C NMR (100
) δ = 141.06, 139.74, 128.27, 127.96, 126.74, 113.78, 59.72, 54.72, 39.34,
MHz, CDCl
3.93, 28.49, 25.62. Spectral data was consistent with the known aminoalkene.
3
5
3
N-benzyl-1-(1-(but-3-enyl)cyclohexyl)methanamine (6g) Compound 6g was
synthesized from cyclohexanenitrile and 4-bromobut-1-ene employing a procedure
1
similar to that used to synthesize 4i. H NMR (400 MHz, CDCl ) δ = 7.35 – 7.00 (m,
3
5
H), 5.90 – 5.70 (m, 1H), 4.94 (dd, J = 30.9, 13.6 Hz, 2H), 3.74 (d, J = 6.0 Hz, 2H),
7

2
.37 (dd, J = 6.4, 4.0 Hz, 2H), 1.85 (d, J = 6.4 Hz, 2H), 1.48 – 1.19 (m, 12H), 0.88
1
3
(
brs, 1H). C NMR (100 MHz, CDCl ) δ = 141.07, 139.91, 128.34, 128.09, 126.84,
3
1
13.88, 55.48, 54.74, 36.02, 35.15, 34.34, 27.61, 26.60, 21.68. Spectral data was
5
consistent with the known aminoalkene.
tert-Butyl
2,2-diphenylpent-4-enylcarbamate
To
a
solution
of
the
2
,2-diphenylpent-4-en-1-amine (2 mmol) in THF (20 mL) at 0 ˚C was added Et
3
N (12
mmol), followed by DMAP (about 0.01 g). To the reaction mixture was added
di-tert-butyl dicarbonate (2.4 mmol) and the solution was stirred at this temperature
for 6 h. At this time the reaction mixture was quenched with ice and water (30 mL)
2 2
and extracted with CH Cl (3×30 mL). The combined organic phases were washed
with brine (20 mL), dried (MgSO ), and concentrated. Chromatography afforded a
4
1
white solid. H NMR (400 MHz, CDCl ) δ = 7.31-7.16 (m, 10H), 5.42 (td, J = 16.4,
3
7
.4 Hz, 1H), 5.07-4.82 (m, 2H), 4.14 (s, 1H), 3.85 (d, J = 5.4 Hz, 2H), 2.86 (d, J = 6.8
1
3
Hz, 2H), 1.38 (s, 9H). C NMR (100 MHz, CDCl
3
) δ = 155.76, 145.50, 133.88,
1
28.24, 128.07, 126.40, 118.48, 79.01, 49.96, 47.18, 41.79, 28.83. Spectral data was
6
consistent with the known aminoalkene.
Benzyl 2,2-diphenylpent-4-enylcarbamate Benzyl chloroformate (2 mmol) was
added slowly to a mixture of 2,2-diphenyl-4-pentenylamine (S2) (2 mmol) and
NaHCO
suspension was stirred for 1 h and treated with water (40 mL). The resulting mixture
was extracted with CH Cl (3×30 mL) and the combined CH Cl extracts were
dried (MgSO ) and concentrated. Chromatography afforded the as a white solid. H
NMR (400 MHz, CDCl
3
(3 mmol) in ethanol/water (3:2, 20 mL) at room temperature. The resulting
2
2
2
2
1
4
3
) δ = 7.54 – 7.36 (m, 9H), 7.34 – 7.26 (m, 6H), 5.69 – 5.53
(
(
m, 1H), 5.17 (s, 2H), 5.14 – 5.10 (m, 2H), 4.59 (s, 1H), 4.09 (d, J = 6.0 Hz, 2H), 3.01
d, J = 7.1 Hz, 2H). Spectral data was consistent with the known aminoalkene.
7
(
9
9H-fluoren-9-yl)methyl 2,2-diphenylpent-4-enylcarbamate
-fluorenylmethyl chloroformate (2 mmol), 2,2-diphenyl-4-pentenylamine (S2) (2.1
mmol), and Et N (3.5 mmol) in CH Cl (20 mL) was stirred for 1 h at room
temperature, treated with water (30 mL), and extracted with CH Cl (3×30 mL).
The combined CH Cl extracts were dried (MgSO ), and concentrated under
vacuum. Chromatography afforded the a white solid. H NMR (400 MHz, CDCl ) δ =
.68 (d, J = 7.3 Hz, 2H), 7.41 (d, J = 7.1 Hz, 2H), 7.31 (t, J = 7.3 Hz, 2H), 7.27 – 7.07
A
solution of
3
2
2
2
2
2
2
4
1
3
7
(
m, 12H), 5.50 – 5.30 (m, 1H), 5.02 – 4.76 (m, 2H), 4.26 (d, J = 6.5 Hz, 3H), 4.09 (d,
8

J = 6.5 Hz, 1H), 3.85 (d, J = 5.0 Hz, 2H), 2.76 (d, J = 6.7 Hz, 2H). Spectral data was
7
consistent with the known aminoalkene.
8
Compounds 8a-8k were synthesized via reported procedures. To a solution of
alkeneamine (1.0 mmol) in 10 mL of dry toluene was added sulfonyl chloride (1.0
mmol) and pyridine (0.5 mL, 2 mmol). The mixture was stirred at 25 °C for 24 h,
diluted with 5 mL of 1 N HCl and was extracted with Et O (330 mL). The combined
2
4
organic layer was dried over MgSO , filtered and concentrated in vacuo. The resulting
oily residue was chromatographed to give desired products.
1
N-(2,2-diphenylpent-4-enyl)methanesulfonamide (8a) H NMR (400 MHz, CDCl )
3
δ = 7.59 – 6.75 (m, 10H), 5.41 – 5.20 (m, 1H), 5.09 – 4.80 (m, 2H), 4.02– 3.97 (d m,
1
3
1
H), 3.69 (d, J = 6.6 Hz, 2H), 2.86 (d, J = 7.0 Hz, 2H), 2.51 (s, 3H). C NMR (100
MHz, CDCl ) δ = 144.91, 133.49, 128.48, 127.95, 126.81, 119.05, 49.73, 49.69, 41.21,
9.78. Spectral data was consistent with the known aminoalkene.
3
9
3
1
N-(2,2-Diphenylpent-4-enyl)-4-methylbenzenesulfonamide (8b) H NMR (400
MHz, CDCl ) δ = 7.59 (d, J=8.2, 2H), 7.39-7.13 (m, 8H), 7.08-7.00 (m, 4H),
.35-5.14 (m, 1H), 5.01-4.86 (m, 2H), 3.88 (t, J=6.5, 1H), 3.52 (d, J=6.5, 2H), 2.89 (d,
3
5
1
3
J=7.1, 2H), 2.41 (s, 3H). C NMR (100 MHz, CDCl
3
) δ = 144.54, 143.37, 136.33,
1
33.16, 129.68, 128.40, 127.71, 127.13, 126.70, 119.08, 49.45, 49.32, 41.27, 21.55.
8
Spectral data was consistent with the known aminoalkene.
1
N-(2,2-diphenylpent-4-enyl)benzenesulfonamide (8c) H NMR (400 MHz, CDCl
3
)
δ = 7.41 (dd, J = 15.4, 7.5 Hz, 2H), 7.35 – 7.09 (m, 8H), 7.06 – 6.81 (m, 5H), 5.36 –
.02 (m, 1H), 4.84 (d, J = 12.2 Hz, 2H), 3.82 (s, 1H), 3.47 (d, J = 6.4 Hz, 2H), 2.81 (d,
5
1
3
J = 7.1 Hz, 2H). C NMR (100 MHz, CDCl
3
) δ = 144.50, 139.25, 133.09, 132.66,
1
29.11, 128.46, 127.75, 127.10, 126.79, 119.10, 49.44, 49.32, 41.26. Spectral data
9
was consistent with the known aminoalkene.
1
N-(2,2-diphenylpent-4-enyl)-4-nitrobenzenesulfonamide (8d) H NMR (400 MHz,
CDCl ) δ = 8.21 (d, J = 8.6 Hz, 2H), 7.76 (d, J = 8.6 Hz, 2H), 7.34 – 7.12 (m, 6H),
.98 (d, J = 6.8 Hz, 4H), 5.23 – 5.13 (m, 1H), 5.01 – 4.72 (m, 2H), 4.02 (t, J = 6.1 Hz,
3
6
1
1
3
3
H), 3.53 (d, J = 6.1 Hz, 2H), 2.82 (d, J = 7.0 Hz, 2H). C NMR (100 MHz, CDCl ) δ
9

=
148.99, 144.16, 143.11, 131.89, 127.54, 127.26, 126.65, 125.97, 123.31, 118.24,
1
0
4
8.53, 48.47, 40.35. Spectral data was consistent with the known aminoalkene.
1
N-(2,2-diphenylpent-4-enyl)-1,1,1-trifluoromethanesulfonamide (8e) H NMR
(
2
400 MHz, CDCl ) δ = 7.62 – 6.79 (m, 10H), 5.41 – 5.19 (m, 1H), 5.01 – 4.88 (m,
3
1
3
H), 4.32 (s, 1H), 3.83 (d, J = 5.0 Hz, 2H), 2.85 (d, J = 7.0 Hz, 2H). C NMR (100
) δ = 143.89, 132.68, 129.24, 128.74, 128.29, 127.79, 127.20, 119.65,
MHz, CDCl
5
(
3
1
9
0.67, 49.73, 42.62, 40.98. F NMR (376 MHz, CDCl ) δ = - 76.53. HRMS–ESI
m/z): M calcd for C18
3
+
H
17
F
3
NO
2
S, 369.1010; found: 369.1063.
1
N-(2,2-dimethylpent-4-enyl)-4-methylbenzenesulfonamide (8f) H NMR (400
MHz, CDCl ) δ = 7.67 (d, J = 8.2 Hz, 2H), 7.23 (d, J = 8.2 Hz, 2H), 5.65 (ddt, J =
3
1
2
1
7.6, 10.3, 7.5 Hz, 1H), 5.06 – 4.75 (m, 2H), 4.66 (s, 1H), 2.60 (d, J = 6.9 Hz, 2H),
1
3
.35 (s, 3H), 1.88 (d, J = 7.5 Hz, 2H), 0.78 (s, 6H). C NMR (100 MHz, CDCl
3
) δ =
43.29, 137.05, 134.29, 129.69, 127.07, 117.87, 52.86, 44.04, 34.12, 24.85, 21.51.
8
Spectral data was consistent with the known aminoalkene.
1
N-((1-allylcyclohexyl)methyl)-4-methylbenzenesulfonamide (8g) H NMR (400
MHz, CDCl ) δ = 7.66 (d, J = 8.2 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 5.80 – 5.47 (m,
H), 5.09 – 4.79 (m, 2H), 4.48 (s, 1H), 2.67 (d, J = 6.9 Hz, 2H), 2.36 (s, 3H), 1.96 (d,
3
1
1
3
J = 7.5 Hz, 2H), 1.46 – 1.09 (m, 10H). C NMR (100 MHz, CDCl
3
) δ = 143.26,
1
2
36.97, 134.13, 129.67, 127.07, 117.82, 49.44, 40.49, 36.35, 33.30, 25.99, 21.51,
1.25. Spectral data was consistent with the known aminoalkene.
8
1
4
7
1
2
-methyl-N-(pent-4-enyl)benzenesulfonamide (8h) H NMR (400 MHz, CDCl ) δ =
3
.68 (d, J = 8.2 Hz, 2H), 7.22 (d, J = 8.2 Hz, 2H), 5.61 (ddt, J = 16.9, 10.2, 6.7 Hz,
H), 5.05 (d, J = 5.2 Hz, 1H), 4.96 – 4.77 (m, 2H), 2.84 (dd, J = 13.5, 6.8 Hz, 2H),
.34 (s, 2H), 1.95 (q, J = 7.1 Hz, 3H), 1.53 – 1.43 (m, 2H). C NMR (100 MHz,
1
3
CDCl ) δ = 143.31, 137.30, 137.02, 129.69, 127.09, 115.43, 42.60, 30.62, 28.65,
3
8
2
1.49.Spectral data was consistent with the known aminoalkene.
1
N-(2,2-diphenylhex-5-enyl)-4-methylbenzenesulfonamide (8i) H NMR (400 MHz,
CDCl ) δ = 7.50 (d, J = 8.3 Hz, 2H), 7.18 – 6.86 (m, 12H), 5.64 – 5.46 (m, 1H), 4.78
dd, J = 11.6, 6.3 Hz, 2H), 3.91 (t, J = 6.4 Hz, 1H), 3.47 (d, J = 6.5 Hz, 2H), 2.29 (s,
3
(
3
1
3
3
H), 2.14 – 2.02 (m, 2H), 1.56 (dd, J = 15.8, 7.2 Hz, 2H). C NMR (100 MHz, CDCl )
δ = 144.91, 143.46, 138.31, 129.79, 128.48, 127.80, 127.14, 126.72, 126.63, 114.63,
10

4
9.69, 49.49, 35.95, 28.33, 21.56. Spectral data was consistent with the known
9
aminoalkene.
1
4
-methyl-N-(5-methyl-2,2-diphenylhex-4-enyl)benzenesulfonamide (8j) H NMR
(
400 MHz, CDCl ) δ = 7.49 (d, J = 8.3 Hz, 2H), 7.27 – 7.08 (m, 8H), 6.98 (dd, J = 8.1,
3
1
2
.3 Hz, 4H), 4.65 (t, J = 7.2 Hz, 1H), 3.77 (t, J = 6.1 Hz, 1H), 3.43 (d, J = 6.3 Hz, 2H),
.73 (d, J = 7.2 Hz, 2H), 2.34 (s, 3H), 1.47 (s, 3H), 1.30 (s, 3H). C NMR (100 MHz,
1
3
CDCl ) δ = 144.76, 143.37, 136.17, 135.50, 129.66, 128.31, 127.93, 127.16, 126.62,
3
1
18.51, 50.16, 49.73, 35.57, 25.95, 21.52, 17.89. Spectral data was consistent with the
11
known aminoalkene.
1
4
-methyl-N-(2-phenylpent-4-enyl)benzenesulfonamide (8k) H NMR (400 MHz,
3
CDCl ) δ = 7.57 (d, J = 8.2 Hz, 2H), 7.33 – 7.11 (m, 5H), 6.95 (d, J = 7.0 Hz, 2H),
5
3
2
1
.52 (ddt, J = 14.0, 10.2, 7.0 Hz, 1H), 4.90 (dd, J = 26.8, 18.0 Hz, 2H), 4.20 (s, 1H),
.33 – 3.12 (m, 1H), 3.04 – 2.84 (m, 1H), 2.78 – 2.62 (m, 1H), 2.39 – 2.30 (m, 3H),
1
3
.30 – 2.17 (m, 2H). C NMR (100 MHz, CDCl
3
) δ = 143.39, 140.99, 136.93, 135.41,
29.70, 128.88, 127.72, 127.18, 127.09, 117.04, 47.76, 45.29, 38.03, 21.53. Spectral
3
data was consistent with the known aminoalkene.
5. General Procedures for Bromoamination
The reaction was carried out in open air system. To a 100 mL flask was added 1
mmol alkenylamine, 1equiv. CuBr
stirred at room temperature for a specified period. Then 30 mL of CH
and the reaction mixture was washed with EDTA (25 mL × 3), dried over MgSO
2
and 20 mL of CH
3
CN. The reaction mixture was
Cl was added
and
2
2
4
was concentrated to give an oil. In most of the reactions, the product obtained was
NMR pure; further silica gel chromatography was not necessary.
1
1
7
3
2
1
-benzyl-5-bromo-3,3-diphenylpiperidine (5a) Oil. H NMR (400 MHz, CDCl
3
) δ =
.26 – 6.98 (m, 15H), 3.87 (ddd, J = 15.3, 8.0, 4.0 Hz, 1H), 3.49 (q, J = 13.2 Hz, 3H),
.18 (dd, J = 10.4, 3.8 Hz, 1H), 3.01 (d, J = 12.5 Hz, 1H), 2.40 (t, J = 12.4 Hz, 1H),
3
) δ = 147.36, 144.80, 137.63, 129.37,
28.71, 128.45, 128.19, 127.54, 126.48, 126.06, 62.57, 62.00, 49.23, 46.80, 45.52.
1
3
.30-2.18 (m, 2H). C NMR (100 MHz, CDCl
+
HRMS–ESI (m/z): [M+H] calcd for C24H24BrN, 406.1170; found: 406.1161.
11

5
1
1
2
-bromo-1-(4-methylbenzyl)-3,3-diphenylpiperidine (5b) White solid. M.p. =
o
1
35-137 C. H NMR (400 MHz, CDCl
3
) δ = 7.44 – 6.89 (m, 15H), 4.09 – 3.79 (m,
H), 3.54 (d, J = 12.4 Hz, 1H), 3.49 (s, 2H), 3.20 (dd, J = 10.5, 4.3 Hz, 1H), 3.08 –
13
.97 (m, 1H), 2.42 (t, J = 12.4 Hz, 1H), 2.28 (s, 3H), 2.29 – 2.21 (m, 2H). C NMR
) δ = 147.41, 144.87, 137.07, 134.50, 129.34, 129.11, 128.75,
(100 MHz, CDCl
3
1
28.44, 128.16, 126.48, 126.46, 126.02, 62.29, 61.98, 61.92, 49.22, 46.85, 45.59,
+
21.32. HRMS–ESI (m/z): [M+H] calcd for C H BrN, 420.1327; found: 420.1226.
2
5
26
5
8
2
3
-bromo-1-(4-methoxybenzyl)-3,3-diphenylpiperidine (5c) White solid. M.p. =
o
8-91 C. H NMR (400 MHz, CDCl ) δ = 7.41 – 6.92 (m, 12H), 6.78 (d, J = 7.7 Hz,
3
1
H), 3.87 (t, J = 11.3 Hz, 1H), 3.71 (s, 3H), 3.51 (d, J = 12.1 Hz, 1H), 3.44 (s, 2H),
.21 – 3.16 (m, 1H), 3.01 (d, J = 12.3 Hz, 1H), 2.40 (t, J = 12.4 Hz, 1H), 2.30 – 2.14
1
3
(
m, 2H). C NMR (100 MHz, CDCl
3
) δ = 159.00, 147.37, 144.80, 130.52, 129.27,
1
4
28.68, 128.41, 128.14, 127.80, 126.44, 125.99, 113.73, 61.97, 61.88, 61.74, 55.34,
9.17, 46.81, 45.59. HRMS–ESI (m/z): [M+H] calcd for C25H26BrNO, 436.1276;
+
found: 436.1263.
5
1
1
1
-bromo-1-(4-fluorobenzyl)-3,3-diphenylpiperidine (5d) White solid. M.p. =
o
1
04-107 C. H NMR (400 MHz, CDCl
3
) δ = 7.46 – 6.62 (m, 14H), 3.83 (dtt, J = 18.5,
0.8, 3.8 Hz, 1H), 3.48 (t, J = 9.1 Hz, 1H), 3.44 (s, 2H), 3.14 (dd, J = 10.4, 4.1 Hz,
1
3
H), 3.01 (d, J = 12.6 Hz, 1H), 2.39 (t, J = 12.4 Hz, 1H), 2.30 – 2.19 (m, 2H). C
NMR (100 MHz, CDCl ) δ = 163.50, 161.06, 147.27, 144.69, 133.37, 133.35, 130.88,
3
1
6
30.80, 128.60, 128.48, 128.23, 126.53, 126.45, 126.11, 115.39, 115.17, 61.98, 61.90,
1
9
3
1.71, 49.21, 46.75, 45.32. F NMR (376 MHz, CDCl ) δ = -114.95. HRMS–ESI
+
(
m/z): [M+H] calcd for C H BrFN, 424.1076; found: 424.1078.
24 23
5
1
-bromo-1-(4-nitrobenzyl)-3,3-diphenylpiperidine (5e) White solid. M.p. =
o
49-151 C. H NMR (400 MHz, CDCl ) δ = 8.10 (d, J = 8.6 Hz, 2H), 7.36 (d, J = 8.6
3
1
Hz, 2H), 7.29 – 7.06(m, 8H), 7.04(d, J = 7.3 Hz, 2H), 3.92 (tt, J = 11.9, 4.0 Hz, 1H),
.66 – 3.50 (m, 3H), 3.12 (dd, J = 10.2, 4.6 Hz, 1H), 3.06 (d, J = 12.8 Hz, 1H), 2.43 –
3
12

1
3
2
3
.29 (m, 3H). C NMR (100 MHz, CDCl ) δ = 146.34, 145.82, 144.40, 143.27,
1
4
28.60, 127.39, 127.26, 127.20, 125.49, 125.23, 125.14, 122.59, 61.15, 60.80, 60.51,
+
8.11, 45.34, 43.56. HRMS–ESI (m/z): [M+H] calcd for C H BrN O , 451.1021;
2
4
23
2
2
found: 451.1010.
o
1
5
-bromo-1-isobutyl-3,3-diphenylpiperidine (5f) White solid. M.p. = 83-85 C.
H
NMR (400 MHz, CDCl ) δ = 7.35 – 7.31 (m, 2H), 7.21 – 7.04 (m, 8H), 3.93 – 3.82
3
(
=
1
m, 1H), 3.50 (d, J = 12.2 Hz, 1H), 3.23 – 3.18 (m, 1H), 3.00 – 2.92 (m, 1H), 2.41 (t, J
12.3 Hz, 1H), 2.21 – 2.14 (m, 2H), 2.09 (dd, J = 5.1, 2.5 Hz, 2H), 1.86 – 1.70 (m,
1
3
H), 0.86 (d, J = 4.4 Hz, 3H), 0.84 (d, J = 4.4 Hz, 3H). C NMR (100 MHz, CDCl
3
)
δ = 147.55, 145.17, 128.82, 128.38, 128.02, 126.46, 126.38, 125.91, 66.68, 63.58,
+
6
2.16, 49.26, 46.98, 45.86, 25.66, 21.19, 20.91. HRMS–ESI (m/z): [M+H] calcd for
26BrN, 372.1327; found: 372.1313.
21
C H
1
5
-bromo-1-isopropyl-3,3-diphenylpiperidine (5g) Oil. H NMR (400 MHz, CDCl
3
)
δ = 7.61 – 7.24 (m, 10H),4.04 – 3.89 (m, 1H), 3.69 (d, J=12.1, 1H), 3.32 (d, J=6.3,
1
3
1
H), 3.18 – 3.07 (m, 2H), 2.63 – 2.40 (m, 3H), 1.25 (d, J=6.6, 3H), 1.22 (d, J=6.6,
1
3
H). C NMR (100 MHz, CDCl
24.8, 56.7, 56.1, 53.6, 53.5, 47.0, 45.4, 16.8, 16.5. HRMS–ESI (m/z): [M+H] calcd
24BrN, 358.1170; found: 358.1167.
3
) δ = 146.7, 144.3, 127.5, 127.3, 127.0, 125.4, 125.3,
+
for C20
H
1
1
-benzyl-5-bromo-3,3-dimethylpiperidine (5h) Oil. H NMR (400 MHz, CDCl ) δ
3
=
7.29 – 7.16 (m, 5H), 4.16 (ddd, J = 15.7, 10.0, 4.5 Hz, 1H), 3.48 (d, J = 13.4 Hz, 1H),
3
=
.35 (d, J = 13.4 Hz, 1H), 3.15 (d, J =6.6 Hz, 1H), 2.35 (d, J = 11.1 Hz, 1H), 2.07 (t, J
10.8 Hz, 1H), 1.99 – 1.94 (m, 1H),1.70 (d, J = 11.0 Hz, 1H), 1.46 (t, J = 12.5 Hz,
13
1
H), 0.99 (s, 3H), 0.80 (s, 3H). C NMR (100 MHz, CDCl
3
) δ = 137.44, 127.61,
1
27.21, 126.01, 63.41, 61.37, 61.20, 48.23, 45.35, 33.36, 28.23, 23.83. HRMS–ESI
+
(
m/z): [M+H] calcd for C14
H20BrN, 282.0857; found: 282.0854.
1
2
-benzyl-4-bromo-2-azaspiro[5.5]undecane (5i) Oil. H NMR (400 MHz, CDCl
3
) δ
=
7.23 – 7.15 (m, 5H), 4.17 (tt, J = 12.0, 4.4 Hz, 1H), 3.48 (d, J = 13.4 Hz, 1H), 3.35
13

(
dd, J = 13.4, 5.4 Hz, 1H), 3.15 (dd, J = 10.5, 4.3 Hz, 1H), 2.65 (d, J = 11.3 Hz, 1H),
2
1
1
.19 (dd, J = 11.0, 1.8 Hz, 1H), 2.12 (t, J = 10.8 Hz, 1H), 1.57 (d, J = 11.3 Hz, 2H),
1
3
.36 – 1.08 (m, 10H). C NMR (100 MHz, CDCl ) δ = 137.56, 127.54, 127.18,
3
25.98, 62.11, 61.28, 45.29, 37.31, 36.07, 31.65, 25.56, 20.50, 20.47. HRMS–ESI
+
(
m/z): [M+H] calcd for C H BrN, 322.1170; found: 322.1168.
1
7
24
1
1
-benzyl-3-bromopiperidine (5j) H NMR (400 MHz, CDCl
3
) δ = 7.46 – 7.02 (m,
5
H), 4.05 (ddd, J = 13.7, 9.6, 4.0 Hz, 1H), 3.46 (s, 2H), 3.01 (d, J = 9.7 Hz, 1H), 2.66
(
1
d, J = 11.2 Hz, 1H), 2.28 (t, J = 10.4 Hz, 1H), 2.22 – 2.11 (m, 1H), 2.04 (t, J = 9.9 Hz,
1
3
H), 1.77 – 1.50 (m, 3H). C NMR (100 MHz, CDCl
3
) δ = 136.84, 127.95, 127.23,
1
26.10, 61.60, 60.76, 51.77, 47.34, 34.63, 24.85. Spectral data was consistent with the
1
2
known compound.
1
3
7
3
2
3
,3-diallyl-1-benzyl-5-bromopiperidine (5k) Oil. H NMR (400 MHz, CDCl ) δ =
.52 – 6.91 (m, 5H), 5.74 – 5.56 (m, 2H), 5.12 – 4.87 (m, 4H), 3.49 – 3.34 (m, 2H),
.11 (ddd, J = 25.1, 10.5, 4.4 Hz, 1H), 2.51 (d, J = 11.5 Hz, 1H), 2.28 – 2.18 (m, 2H),
.07 (dd, J = 13.7, 7.9 Hz, 1H), 2.02 – 1.88 (m, 1H), 1.91 – 1.79 (m, 2H), 1.73 (d, J =
1
3
1
1.3 Hz, 1H), 1.54 – 1.42 (m, 1H), 1.31 – 1.20 (m, 1H). C NMR (100 MHz, CDCl
3
)
δ = 137.27, 133.10, 132.22, 127.78, 127.25, 126.12, 117.20, 116.93, 61.34, 61.29,
+
6
0.12, 44.77, 44.06, 41.82, 39.14, 36.95. HRMS–ESI (m/z): [M+H] calcd for
18
C H14BrN, 334.1170; found: 334.1165.
1
1
-benzyl-2-(bromomethyl)-5,5-diphenylpiperidine (7a) Oil. H NMR (400 MHz,
CDCl ) δ = 7.67 – 7.13 (m, 15H), 4.09 (d, J = 13.1 Hz, 1H), 3.69 – 3.58 (m, 2H), 3.35
dd, J = 17.1, 12.9 Hz, 2H), 2.75 (s, 1H), 2.63 (d, J = 12.4 Hz, 1H), 2.50 (d, J = 13.0
3
(
13
Hz, 1H), 2.39 – 2.18 (m, 1H), 1.86 – 1.67 (m, 2H). C NMR (100 MHz, CDCl ) δ =
3
1
1
47.79, 146.52, 138.41, 129.54, 129.25, 128.31, 128.27, 128.06, 127.79, 127.20,
25.88, 125.63, 60.46, 60.08, 58.95, 46.31, 34.66, 33.10, 26.32. HRMS–ESI (m/z):
+
[M+H] calcd for C25
H26BrN, 420.1327; found: 420.1225.
14

1
2
-(bromomethyl)-1-(4-methylbenzyl)-5,5-diphenylpiperidine（7b）Oil. H NMR
(
400 MHz, CDCl ) δ = 7.45 – 7.01 (m, 14H), 3.98 (d, J = 13.1 Hz, 1H), 3.57 (d, J =
3
4
8
2
1
6
.9 Hz, 2H), 3.30 (dd, J = 12.4, 1.2 Hz, 1H), 3.24 (d, J = 13.1 Hz, 1H), 2.67 (td, J =
.9, 4.7 Hz, 1H), 2.56 (d, J = 12.4 Hz, 1H), 2.47 – 2.38 (m, 1H), 2.36 (s, 3H), 2.28 –
1
3
.19 (m, 1H), 1.79 – 1.64 (m, 2H). C NMR (100 MHz, CDCl ) δ = 147.82, 146.59,
3
36.82, 135.21, 129.40, 128.91, 128.31, 127.99, 127.73, 127.21, 125.80, 125.56,
+
0.35, 59.97, 58.60, 46.29, 34.56, 33.07, 26.26, 21.18. HRMS–ESI (m/z): [M+H]
calcd for C26H28BrN, 434.1483; found: 4354.1478.
1
2
-(bromomethyl)-1-(4-methoxybenzyl)-5,5-diphenylpiperidine (7c) Oil. H NMR
(
400 MHz, CDCl ) δ = 7.22 (d, J = 8.5 Hz, 2H), 7.18 – 7.08 (m, 6H), 7.06 – 6.96 (m,
3
4
2
H), 6.82 (d, J = 8.5 Hz, 2H), 3.90 (d, J = 13.0 Hz, 1H), 3.75 (s, 3H), 3.56 – 3.45 (m,
H), 3.22 (d, J = 12.4 Hz, 1H), 3.14 (d, J = 13.0 Hz, 1H), 2.65 – 2.55 (m, 1H), 2.47 (d,
13
J = 12.4 Hz, 1H), 2.41 – 2.31 (m, 1H), 2.22 – 2.10 (m, 1H), 1.70 – 1.60 (m, 2H). C
NMR (100 MHz, CDCl ) δ = 158.88, 147.81, 146.56, 130.61, 130.32, 128.29, 128.00,
27.73, 127.19, 125.80, 125.55, 113.59, 60.32, 59.77, 58.13, 55.28, 46.27, 34.58,
3
1
3
4
+
3.08, 26.28. HRMS–ESI (m/z): [M+H] calcd for C26
H28BrNO, 450.1433; found:
50.1420.
1
2
-(bromomethyl)-1-(4-fluorobenzyl)-5,5-diphenylpiperidine (7d) Oil. H NMR
3
(400 MHz, CDCl ) δ = 7.41 (dd, J = 8.2, 5.8 Hz, 2H), 7.30 – 7.22 (m, 6H), 7.20 –
7
1
2
1
1
1
.05 (m, 6H), 4.06 (d, J = 13.1 Hz, 1H), 3.67 (dd, J = 10.6, 6.8 Hz, 1H), 3.60 (dd, J =
0.6, 2.5 Hz, 1H), 3.35 (dd, J = 12.3, 1.1 Hz, 1H), 3.26 (d, J = 13.1 Hz, 1H), 2.80 –
.68 (m, 1H), 2.60 (d, J = 12.3 Hz, 1H), 2.50 (dt, J = 7.9, 3.5 Hz, 1H), 2.36 – 2.26 (m,
H), 1.87 – 1.73 (m, 2H). C NMR (100 MHz, CDCl ) δ = 164.12, 161.68, 148.43,
3
47.09, 134.83, 134.80, 131.77, 131.70, 128.95, 128.81, 128.52, 127.82, 126.65,
1
3
26.38, 115.89, 115.68, 61.14, 60.67, 58.72, 46.98, 35.35, 33.83, 27.08. 19F NMR
+
(376 MHz, CDCl
3
) δ = -115.52. HRMS–ESI (m/z): [M+H] calcd for C25
H25BFrN,
4
38.1233; found: 438.1227.
1
2
-(bromomethyl)-1-(4-chlorobenzyl)-5,5-diphenylpiperidine (7e) Oil. H NMR
) δ = 7.32 (s, 4H), 7.24 – 7.15 (m, 6H), 7.14 – 7.06 (m, 4H), 3.99 (d,
J = 13.3 Hz, 1H), 3.59 (dd, J = 10.6, 6.7 Hz, 1H), 3.53 (dd, J = 10.6, 2.7 Hz, 1H), 3.29
dd, J = 12.3, 1.4 Hz, 1H), 3.21 (d, J = 13.3 Hz, 1H), 2.72 – 2.63 (m, 1H), 2.55 (d, J =
(400 MHz, CDCl
3
(
15

1
3
1
2.3 Hz, 1H), 2.49 – 2.39 (m, 1H), 2.31 – 2.20 (m, 1H), 1.79 – 1.69 (m, 2H). C
NMR (100 MHz, CDCl ) δ = 147.63, 146.27, 136.97, 133.01, 130.75, 128.38, 128.19,
3
1
28.07, 127.79, 127.05, 125.91, 125.65, 60.50, 60.16, 58.14, 46.27, 34.51, 33.08,
+
26.36. HRMS–ESI (m/z): [M+H] calcd for C25
H25BrClN, 454.0937; found: 454.0934.
1
1
-benzyl-2-(bromomethyl)-5,5-dimethylpiperidine (7f) Oil. H NMR (400 MHz,
CDCl ) δ = 7.36 (d, J = 7.4 Hz, 2H), 7.29 (t, J = 7.4 Hz, 2H), 7.26 – 7.20 (m, 1H),
3
3
1
1
1
1
2
.97 (d, J = 13.5 Hz, 1H), 3.66 (dd, J = 10.6, 6.5 Hz, 1H), 3.52 (dd, J = 10.6, 2.0 Hz,
H), 3.19 (d, J = 13.5 Hz, 1H), 2.49 (s, 1H), 2.32 (d, J = 11.3 Hz, 1H), 1.91 (ddd, J =
3.2, 11.1, 4.3 Hz, 1H), 1.80 (d, J = 11.4 Hz, 1H), 1.72 – 1.62 (m, 1H), 1.46 – 1.36 (m,
1
3
H), 1.28 – 1.17 (m, 1H), 0.93 (s, 3H), 0.83 (s, 3H). C NMR (100 MHz, CDCl ) δ =
3
39.61, 128.49, 128.13, 126.74, 62.38, 60.56, 57.96, 35.77, 35.29, 30.61, 28.07, 26.60,
+
5.50. HRMS–ESI (m/z): [M+H] calcd for C H BrN, 296.1014; found: 296.1013.
1
5
22
1
2
-benzyl-3-(bromomethyl)-2-azaspiro[5.5]undecane (7g) Oil. H NMR (400 MHz,
) δ = 7.49 – 7.09 (m, 5H), 3.97 (d, J = 13.4 Hz, 1H), 3.67 (dd, J = 10.6, 6.4 Hz,
H), 3.51 (dd, J = 10.6, 1.9 Hz, 1H), 3.15 (d, J = 13.4 Hz, 1H), 2.50 (d, J = 11.3 Hz,
H), 1.95 – 1.84 (m, 1H), 1.79 (d, J = 11.5 Hz, 1H), 1.69 – 1.49 (m, 2H), 1.47 – 1.11
CDCl
1
2
3
1
3
(
m, 11H). C NMR (100 MHz, CDCl
3
) δ = 139.73, 128.53, 128.10, 126.75, 61.23,
5
7.98, 36.85, 35.59, 33.68, 32.92, 26.81, 25.85, 21.58, 21.55. HRMS–ESI (m/z):
+
[M+H] calcd for C18H26BrN, 336.1327; found: 336.1325.
2
-(bromomethyl)-1-(methylsulfonyl)-4,4-diphenylpyrrolidine (9a) White solid.
o
1
M.p. = 143-145 C. H NMR (400 MHz, CDCl
11.0, 1.7 Hz, 1H), 4.09 (d, J = 11.0 Hz, 1H), 3.97 (ddd, J = 14.7, 7.9, 2.6 Hz, 1H),
.68 (dd, J = 10.1, 2.9 Hz, 1H), 3.35 (dd, J = 10.1, 8.3 Hz, 1H), 3.15 (ddd, J = 13.3,
3
) δ = 7.41 – 6.91 (m, 10H), 4.22 (dd, J
=
3
6
1
3
.9, 1.6 Hz, 1H), 2.53 (dd, J = 13.4, 8.3 Hz, 1H), 2.30 (s, 3H). C NMR (100 MHz,
) δ = 144.60, 144.12, 129.01, 128.81, 127.22, 126.92, 126.84, 126.46, 59.85,
CDCl
3
+
59.49, 53.25, 42.69, 36.72, 36.58. HRMS–ESI (m/z): [M+H] calcd for C18
2
H20BrNO S,
3
94.0476; found: 394.0468.
16

1
2
-(bromomethyl)-4,4-diphenyl-1-tosylpyrrolidine (9b) H NMR (400 MHz, CDCl
δ = 7.53 (d, J = 8.0 Hz, 2H), 7.25 – 6.85 (m, 12H), 4.33 (d, J = 10.2 Hz, 1H), 3.96 –
.81 (m, 1H), 3.72 (dd, J = 9.7, 3.1 Hz, 1H), 3.63 (d, J = 10.2 Hz, 1H), 2.86 (t, J = 9.9
3
)
3
1
3
Hz, 1H), 2.67 (qd, J = 13.2, 6.5 Hz, 2H), 2.30 (s, 3H). C NMR (100 MHz, CDCl )
3
δ= 144.70, 144.44, 143.76, 133.82, 129.85, 128.77, 128.70, 127.45, 126.84, 126.61,
+
1
26.56, 126.36, 60.08, 58.87, 52.29, 42.04, 35.90, 21.59. HRMS–ESI (m/z): [M+H]
calcd for C24
with the known compound.
H
2
24BrNO S, 470.0789; found: 470.0789. Spectral data was consistent
1
3
2
-(bromomethyl)-4,4-diphenyl-1-(phenylsulfonyl)pyrrolidine (9c) White solid.
o
1
M.p. = 162-163 C. H NMR (400 MHz, CDCl
.4 Hz, 1H), 7.36 (t, J = 7.7 Hz, 2H), 7.25 – 7.17 (m, 4H), 7.16 – 6.98 (m, 6H), 4.32
d, J = 10.2 Hz, 1H), 3.94 – 3.80 (m, 1H), 3.80 – 3.60 (m, 2H), 2.89 (t, J = 9.9 Hz,
3
) δ = 7.70 – 7.64 (m, 2H), 7.46 (t, J =
7
(
1
1
5
1
3
H), 2.78 – 2.57 (m, 2H). C NMR (100MHz, CDCl
3
) δ = 144.55, 144.34, 137.10,
32.91, 129.18, 128.76, 128.71, 127.39, 126.86, 126.76, 126.59, 126.30, 60.03, 58.81,
+
2
2.30, 42.11, 35.69. HRMS–ESI (m/z): [M+H] calcd for C23H22BrNO S, 456.0633;
found: 456.0625.
2
-(bromomethyl)-1-(4-nitrophenylsulfonyl)-4,4-diphenylpyrrolidine (9d) White
o
1
solid. M.p. = 165-167 C. H NMR (400 MHz, CDCl
3
) δ = 8.04 (d, J = 8.8 Hz, 2H),
7
1
3
.69 (d, J = 8.8 Hz, 2H), 7.29 – 6.91 (m, 10H), 4.26 (d, J = 10.8 Hz, 1H), 4.04 (d, J =
0.8 Hz, 1H), 3.96 (ddd, J = 10.3, 7.9, 2.9 Hz, 1H), 3.79 (dd, J = 10.1, 2.9 Hz, 1H),
.31 (dd, J = 9.9, 8.8 Hz, 1H), 3.00 (dd, J = 13.4, 7.1 Hz, 1H), 2.50 (dd, J = 13.5, 7.7
1
3
Hz, 1H). C NMR (100 MHz, CDCl ) δ =149.93, 144.50, 143.49, 143.30, 128.82,
3
1
3
5
28.76, 128.10, 126.99, 126.78, 126.41, 126.33, 124.20, 60.09, 59.99, 52.77, 42.48,
6.16. HRMS–ESI (m/z): [M+H] calcd for C23H21BrN O S, 501.0484; found:
2 4
01.0464.
+
17

1
2
-(bromomethyl)-4,4-dimethyl-1-tosylpyrrolidine (9f) H NMR (400 MHz, CDCl
3
)
δ = 7.67 (d, J = 8.2 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 3.86 (dd, J = 9.6, 3.0 Hz, 1H),
3
2
0
.80 (ddd, J = 15.9, 8.3, 3.0 Hz, 1H), 3.45 (t, J = 9.1 Hz, 1H), 3.10 (q, J = 10.9 Hz,
H), 2.36 (s, 3H), 1.81 (dd, J = 12.9, 7.2 Hz, 1H), 1.63 (dd, J = 12.9, 8.2 Hz, 1H),
1
3
.98 (s, 3H), 0.46 (s, 3H). C NMR (100 MHz, CDCl ) δ=143.73, 134.88, 129.73,
3
1
27.53, 61.88, 60.02, 45.86, 37.52, 37.47, 26.09, 25.79, 21.56. Spectral data was
1
4
consistent with the known compound.
1
3
-(bromomethyl)-2-tosyl-2-azaspiro[4.5]decane (9g) H NMR (400 MHz, CDCl
3
) δ
=
7.67 (d, J = 8.2 Hz, 2H), 7.25 (d, J = 8.1 Hz, 2H), 3.86 (dd, J = 9.7, 3.0 Hz, 1H),
3
3
1
0
.73 (ddd, J = 16.1, 8.4, 3.0 Hz, 1H), 3.46 – 3.40 (m, 1H), 3.27 (d, J = 10.9 Hz, 1H),
.07 (d, J = 10.9 Hz, 1H), 2.36 (s, 3H), 1.86 (dt, J = 49.9, 24.9 Hz, 1H), 1.56 (dd, J =
3.1, 8.4 Hz, 1H), 1.35 – 0.98 (m, 8H), 0.73 (ddd, J = 13.0, 9.2, 3.8 Hz, 1H), 0.64 –
1
3
.53 (m, 1H). C NMR (100 MHz, CDCl ) δ = 143.69, 134.75, 129.70, 127.49, 59.29,
3
5
9.09, 44.08, 41.43, 37.72, 36.16, 34.01, 25.77, 23.69, 22.79, 21.54. Spectral data was
1
4
consistent with the known compound.
1
2
-(bromomethyl)-1-tosylpyrrolidine (9h) H NMR (400 MHz, CDCl
3
) δ = 7.65 (d, J
=
8.3 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 3.75 (ddd, J = 11.6, 7.6, 3.6 Hz, 1H), 3.68 (dd,
J = 9.9, 3.1 Hz, 1H), 3.42 – 3.35 (m, 1H), 3.29 (t, J = 9.7 Hz, 1H), 3.08 (dt, J = 9.9,
.1 Hz, 1H), 2.36 (s, 3H), 1.90 – 1.81 (m, 1H), 1.76 (dt, J = 18.7, 5.9 Hz, 1H), 1.67
7
1
3
(
ddd, J = 12.4, 7.6, 4.2 Hz, 1H), 1.56 – 1.36 (m, 1H). C NMR (100 MHz, CDCl
3
) δ
=
143.87, 133.98, 129.87, 127.51, 60.37, 49.83, 36.15, 30.26, 23.80, 21.55. Spectral
1
4
data was consistent with the known compound.
2
-(bromomethyl)-5,5-diphenyl-1-tosylpiperidine (9i) White solid. M.p. = 134-135
o
1
C. H NMR (400 MHz, CDCl
.21 – 7.06 (m, 10H), 4.54 (d, J = 13.4 Hz, 1H), 4.03 – 3.94 (m, 1H), 3.45 (t, J = 10.8
Hz, 1H), 3.26 (dd, J = 9.9, 3.2 Hz, 1H), 3.08 (d, J = 13.4 Hz, 1H), 2.40 (dd, J = 14.1,
3
) δ = 7.49 (d, J = 8.2 Hz, 2H), 7.27 (d, J = 7.9 Hz, 2H),
7
2
1
1
5
.4 Hz, 1H), 2.33 (s, 3H), 2.17 (td, J = 14.0, 2.9 Hz, 1H), 2.07 (dd, J = 14.2, 1.8 Hz,
1
3
H), 1.59 (t, J = 12.0 Hz, 1H). C NMR (100 MHz, CDCl ) δ = 145.86, 142.76,
3
42.24, 135.54, 128.84, 127.54, 127.44, 126.77, 126.43, 125.61, 125.29, 125.10,
+
2.09, 47.55, 44.56, 27.61, 27.37, 20.74, 20.52. HRMS–ESI (m/z): [M+H] calcd for
25 2
C H26BrNO S, 484.0946; found: 484.0937.
18

2
8
2
5
1
3
1
4
-(2-bromopropan-2-yl)-4,4-diphenyl-1-tosylpyrrolidine (9j) White solid. M.p. =
9-90 C. H NMR (400 MHz, CDCl ) δ = 7.46 (d, J = 7.6 Hz, 2H), 7.33 (t, J = 7.7 Hz,
3
o
1
H), 7.21 (dt, J = 12.3, 6.3 Hz, 3H), 7.17 – 7.11 (m, 5H), 7.01 (d, J = 8.1 Hz, 2H),
.16 (dd, J = 13.8, 2.6 Hz, 1H), 4.09 (dd, J = 13.0, 3.7 Hz, 1H), 3.55 (d, J = 13.8 Hz,
H), 3.15 (dt, J = 14.0, 3.2 Hz, 1H), 2.65 (t, J = 13.5 Hz, 1H), 2.28 (s, 3H), 1.33 (s,
1
3
H), 1.30 (s, 3H). C NMR (100 MHz, CDCl ) δ = 146.11, 143.12, 142.78, 140.10,
3
29.49, 129.02, 128.71, 127.93, 127.20, 126.79, 126.61, 125.96, 61.82, 58.17, 49.97,
8.80, 42.98, 27.87, 21.42, 16.29. HRMS–ESI (m/z): [M+H]+ calcd for
26 2
C H28BrNO S, 498.1102; found: 498.1101.
o
2
-(bromomethyl)-4-phenyl-1-tosylpyrrolidine (9k) White solid. M.p. = 114-116 C.
1
H NMR (400 MHz, CDCl
.23 – 7.10 (m, 3H), 7.06 – 6.96 (m, 2H), 3.90 (tt, J = 16.5, 8.1 Hz, 1H), 3.82 – 3.75
m, 2H), 3.52 (dd, J = 9.7, 8.4 Hz, 1H), 3.30 (t, J = 11.4 Hz, 1H), 2.57 (ddd, J = 18.4,
3
) δ = 7.70 (d, J = 8.2 Hz, 2H), 7.27 (d, J = 8.1 Hz, 2H),
7
(
1
13
1.6, 7.0 Hz, 1H), 2.46 – 2.33 (m, 4H), 1.92 (td, J = 12.3, 9.0 Hz, 1H). C NMR (100
3
MHz, CDCl ) δ = 144.04, 138.83, 134.90, 130.03, 128.73, 127.52, 127.26, 127.01,
6
0.51, 55.66, 43.10, 39.09, 37.57, 21.62. S–ESI (m/z): [M+H]+ calcd for
C
18
H
20BrNO
2
S, 393.0476; found: 394.0476.
Table 4. Bromoamination of carbamate substrates.
a
a
Entry
R
Conversion
>99
Selectivity(9:9’)
1
2
3
Boc
Cbz
Fmoc
1.1:1
1:0.8
1:1
90
>99
1
a: Determined by H NMR analysis.
19

6
. Derivatization of Bromoamination Product
6.1 Nucleophilic substitution reaction of 7a
Ph
Ph
Ph
Ph
Nucleophile
Br
CH CN
reflux
3
Nu
N
N
Bn
Bn
7a
10-15
1
-benzyl-2-(bromomethyl)-5,5-diphenylpiperidine (7a) was dissolved in 20 ml of
acetonitrile, the nucleophile of interest was added, and the reaction mixture was
heated to reflux overnight. Then 30 mL of CH Cl was added and reaction mixture
2
2
was washed with water, dried over MgSO , and concentrated. The resulting residue
4
was isolated by silica gel chromatography.
1
N-benzyl-1-(1-benzyl-5,5-diphenylpiperidin-2-yl)methanamine (10) Oil. H NMR
(400 MHz, CDCl
3
) δ = 7.39 – 6.72 (m, 20H), 3.98 (d, J = 13.3 Hz, 1H), 3.68 – 3.60
(
m, 2H), 3.34 (dd, J = 12.2, 1.7 Hz, 1H), 3.04 (d, J = 13.3 Hz, 1H), 2.80 (dd, J = 11.9,
5
1
.6 Hz, 1H), 2.70 (dd, J = 11.9, 2.8 Hz, 1H), 2.40 (d, J = 10.1 Hz, 2H), 2.33 (d, J =
1
3
2.3 Hz, 1H), 2.13 – 1.98 (m, 1H), 1.84 (brs, 1H), 1.71 – 1.56 (m,2H). C NMR (100
) δ = 148.50, 146.24, 140.26, 139.03, 129.40, 128.51, 128.35, 128.17,
28.05, 128.02, 127.77, 127.05, 126.92, 126.90, 125.80, 125.43, 61.48, 60.88, 58.94,
MHz, CDCl
3
1
5
4
+
34 2
4.24, 46.28, 34.28, 29.74, 26.68.HRMS–ESI (m/z): [M+H] calcd for C32H N ,
77.2800; found: 477.2797.
1
1
-benzyl-2-(phenoxymethyl)-5,5-diphenylpiperidine (11) Oil. H NMR (400 MHz,
CDCl ) δ = 7.86 – 7.64 (m, 3H), 7.39 (t, J = 7.6 Hz, 3H), 7.23 – 6.97 (m, 12H), 6.75 (t,
3
J = 9.1 Hz, 2H), 4.18 – 4.04 (m, 2H), 3.92 – 3.80 (m, 1H), 3.31 (t, J = 13.9 Hz, 2H),
2
1
.81 (dd, J = 9.0, 4.2 Hz, 1H), 2.50 (d, J = 12.4 Hz, 1H), 2.43 (dd, J = 13.1, 2.4 Hz,
H), 2.22 – 2.12 (m, 1H), 1.78 (ddd, J = 13.3, 6.0, 3.4 Hz, 1H), 1.53 – 1.41 (m, 1H).
C NMR (100 MHz, CDCl ) δ = 158.79, 148.11, 139.21, 132.43, 130.09, 129.46,
3
1
3
1
6
4
28.35, 128.31, 128.13, 128.05, 127.78, 127.09, 125.52, 120.75, 114.57, 70.34, 61.10,
+
0.15, 59.70, 46.28, 33.80, 26.38.HRMS–ESI (m/z): [M+H] calcd for C H NO,
3
1
31
34.2484; found: 434.2477.
o
2
-(azidomethyl)-1-benzyl-5,5-diphenylpiperidine (12) White solid. M.p. = 80-83 C.
H NMR (400 MHz, CDCl ) δ = 7.71 – 6.48 (m, 15H), 4.00 (d, J = 13.4 Hz, 1H), 3.37
3
1
20

(
d, J = 5.1 Hz, 2H), 3.29 (dd, J = 12.4, 1.5 Hz, 1H), 3.20 (d, J = 13.4 Hz, 1H), 2.51 (td,
J = 8.9, 4.8 Hz, 1H), 2.42 (d, J = 12.4 Hz, 1H), 2.39 – 2.37 (m, 1H), 2.23 – 2.03 (m,
1
3
1
H), 1.77 – 1.60 (m, 1H), 1.46 (ddd, J = 16.5, 13.0, 3.3 Hz, 1H). C NMR (100 MHz,
CDCl ) δ = 147.96, 146.20, 138.51, 129.31, 129.23, 128.35, 128.29, 128.08, 127.83,
27.77, 127.28, 127.03, 125.89, 125.61, 60.99, 60.33, 59.40, 52.81, 46.28, 33.58,
3
1
2
+
6.44. HRMS–ESI (m/z): [M+H] calcd for C H N , 383.2236; found: 383.2233.
2
5
26
4
1
1
-benzyl-5,5-diphenyl-2-(p-tolylthiomethyl)piperidine (13) Oil. H NMR (400
) δ = 7.58 – 6.57 (m, 19H), 3.97 (d, J = 13.2 Hz, 1H), 3.27 – 3.07 (m,
H), 3.02 (dd, J = 12.3, 8.2 Hz, 1H), 2.64 (s, 1H), 2.50 (d, J = 12.3 Hz, 1H), 2.31 (s,
MHz, CDCl
3
1
3
1
3
H), 2.20 (s, 3H), 2.16 – 2.06 (m, 1H), 1.67 (ddd, J = 21.7, 10.9, 7.1 Hz, 2H). C
NMR (100 MHz, CDCl ) δ = 147.96, 146.90, 138.86, 136.01, 133.61, 130.05, 129.73,
3
1
5
29.56, 128.25, 128.23, 128.04, 127.89, 127.39, 127.22, 125.81, 125.65, 60.20, 59.40,
9.10, 46.39, 36.05, 33.26, 26.78, 21.10. HRMS–ESI (m/z): [M+H] calcd for
+
32
C H33NS, 464.2412; found: 464.2404.
1
(
1-benzyl-5,5-diphenylpiperidin-2-yl)methyl acetate (14) Oil. H NMR (400 MHz,
CDCl ) δ = 7.57 – 6.80 (m, 15H), 4.20 (dd, J = 11.5, 4.5 Hz, 1H), 4.12 (dd, J = 11.5,
.3 Hz, 1H), 4.02 (d, J = 13.4 Hz, 1H), 3.28 (d, J = 12.5 Hz, 1H), 3.22 (d, J = 13.4 Hz,
H), 2.59 (dt, J = 33.6, 16.8 Hz, 1H), 2.45 (d, J = 12.5 Hz, 1H), 2.39 (d, J = 13.1 Hz,
3
5
1
1
1
3
H), 2.19 – 2.09 (m, 1H), 1.94 (s, 3H), 1.71 – 1.61 (m, 2H). C NMR (100 MHz,
) δ = 170.97, 147.99, 146.43, 138.85, 135.96, 129.43, 129.23, 128.34, 128.28,
28.18, 128.06, 127.77, 127.12, 125.85, 125.55, 65.57, 60.80, 59.47, 46.26, 42.64,
CDCl
1
3
3
+
2
3.56, 25.92, 21.01. HRMS–ESI (m/z): [M+H] calcd for C27H29NO , 400.2277;
found: 400.2276.
1
2
7
3
3
-(Bromomethyl)-5,5-diphenylpiperidine (15) Oil. H NMR (400 MHz, CDCl ) δ =
.73 – 6.84 (m, 10H), 4.03 (dd, J = 13.1, 2.8 Hz, 1H), 3.50 (dd, J = 10.0, 4.1 Hz, 1H),
.36 (dd, J = 10.0, 7.3 Hz, 1H), 3.18 (d, J = 13.1 Hz, 1H), 3.04 (ddd, J = 14.3, 7.0, 3.5
Hz, 1H), 2.80 – 2.72 (m, 1H), 2.31 (td, J = 13.3, 3.5 Hz, 1H), 1.81 – 1.73 (m, 1H),
1
3
1
1
3
3
.41 (ddd, J = 24.3, 13.2, 3.3 Hz, 1H), 1.33 (s, 1H). C NMR (100 MHz, CDCl
3
) δ =
48.24, 144.61, 128.50, 128.37, 128.30, 126.48, 126.05, 125.89, 57.18, 55.35, 45.39,
8.70, 34.97, 27.50. HRMS–ESI (m/z): [M+H] calcd for C18H20BrN, 330.0857; found:
+
30.0850.
21

6.2 Nucleophilic substitution reaction of 5a
Table 5. Nucleophilic substitution of 5a.
Ph
Ph
Ph
Ph
Ph
Ph
Br
Nu
Nucleophile
CH CN
reflux
+
Nu
3
N
N
N
Bn
Bn
16'
Bn
5a
1
6
Entry
Nucleophile
16’
16
49
50
60
65
45
1
2
3
4
5
BnNH
2
24
30
24
17
37
KOAc
NaN3
NaCN
PhSNa
6
.3 Nucleophilic substitution reaction of 15b
Ph
Ph
Ph
Ph
Nucleophile
Br
Nu
N
N
CH CN
3
reflux
Ts
Ts
17-20
9b
1
2
-(Phenoxymethyl)-4,4-diphenyl-1-tosylpyrrolidine (17) Oil. H NMR (400 MHz,
) δ = 7.54 (d, J = 8.2 Hz, 2H), 7.26 – 7.00 (m, 15H), 6.67 (d, J = 7.8 Hz, 2H),
.27 (d, J = 10.1 Hz, 1H), 4.21 (dd, J = 9.4, 3.5 Hz, 1H), 3.98 – 3.90 (m, 1H), 3.73 (d,
J = 10.1 Hz, 1H), 3.49 (t, J = 9.1 Hz, 1H), 2.73 (dd, J = 13.0, 5.3 Hz, 1H), 2.66 (dd, J
CDCl
4
3
13
=
13.0, 7.9 Hz, 1H), 2.27 (s, 3H). C NMR (100 MHz, CDCl ) δ = 158.27, 145.04,
3
1
1
44.83, 143.44, 134.24, 129.68, 129.39, 128.65, 128.62, 127.38, 126.73, 126.64,
26.49, 126.46, 120.88, 114.49, 68.96, 58.37, 57.93, 52.57, 40.84, 21.49. HRMS–ESI
+
(
m/z): [M+H] calcd for C30
H29NO
3
S, 484.1946; found: 484.1935.
2
1
1
–
-(Azidomethyl)-4,4-diphenyl-1-tosylpyrrolidine (18) White solid. M.p. =
o
1
71-172 C. H NMR (400 MHz, CDCl
3
) δ = 7.53 (t, J = 8.4 Hz, 2H), 7.26 – 6.94 (m,
4H), 4.34 (dd, J = 10.2, 6.3 Hz, 1H), 3.91 – 3.78 (m, 1H), 3.74 – 3.67 (m, 1H), 3.65
1
3
3
3.57 (m, 1H), 2.92 – 2.52 (m, 3H), 2.32 (s, 3H). C NMR (100 MHz, CDCl )
22

δ=144.65, 144.46, 143.70, 129.80, 129.78, 128.74, 128.66, 127.44, 127.38, 126.81,
+
126.59, 126.33, 60.06, 58.82, 52.26, 42.05, 35.79, 21.53. HRMS–ESI (m/z): [M+H]
calcd for C24 S, 433.1698; found: 433.1688.
24 4 2
H N O
4
1
6
1
1
1
1
,4-diphenyl-2-(p-tolylthiomethyl)-1-tosylpyrrolidine (19) White solid. M.p. =
o
34-136 C. H NMR (400 MHz, CDCl ) δ = 7.31 (d, J = 8.2 Hz, 2H), 7.26 – 7.17 (m,
3
1
H), 7.11 – 6.91 (m, 10H), 4.41 (d, J = 10.1 Hz, 1H), 3.67 – 3.49 (m, 2H), 3.37 (d, J =
0.1 Hz, 1H), 2.59 (qd, J = 13.0, 6.0 Hz, 2H), 2.30 (s, 3H), 2.29 (s, 3H), 2.14 (dd, J =
1
3
3.4, 11.1 Hz, 1H). C NMR (100 MHz, CDCl ) δ = 144.97, 143.45, 136.49, 133.15,
3
31.27, 130.53, 129.87, 129.64, 128.69, 128.61, 127.59, 126.84, 126.67, 126.48,
+
26.40, 58.68, 52.19, 41.80, 38.65, 21.55, 21.14. HRMS–ESI (m/z): [M+H] calcd for
C H NO S , 514.1874; found: 514.1863.
3
1
31
2 2
1
3
,3-Diphenyl-1-azabicyclo[3.1.0]hexane (20) Oil. H NMR (400 MHz, CDCl
3
) δ =
7.28 – 6.95 (m, 10H), 4.33 (d, J = 10.0 Hz, 1H), 3.67 (d, J = 10.0 Hz, 1H), 3.59 (dd, J
=
=
10.0, 3.2 Hz, 1H), 3.42 (qd, J = 8.4, 3.1 Hz, 1H), 3.17 (t, J = 9.5 Hz, 1H), 2.89 (dd, J
13.4, 8.4 Hz, 1H), 2.37 (dd, J = 13.4, 8.0 Hz, 1H). C NMR (100 MHz, CDCl ) δ =
3
1
3
1
4
2
48.19, 146.69, 137.52, 130.30, 128.62, 128.38, 127.03, 126.96, 75.70, 73.48, 52.72,
3.10, 33.43. HRMS–ESI (m/z): [M+H] calcd for C17H17N, 236.1439; found:
36.1432.
+
23

7
. Copies of NMR Spectra
Ph Ph
CN
24

25

26

27

28