Supporting Information for Formal Synthesis of Chelamidine Alkaloid and Derivatives Table of ...

59 Pages·2017·5.73 MB·English

Electronic Supplementary Material (ESI) for ChemComm.
This journal is © The Royal Society of Chemistry 2018

Supporting Information for

Formal Synthesis of Chelamidine Alkaloid and Derivatives

Rui-Qi Li,a Yu He,a Yao Ding,a Chee-Kiat Ang,b Jie-Sheng Tian,*,a and Teck-Peng Loh*,a,b

aInstitute of Advanced Synthesis (IAS), School of Chemistry and Molecular Engineering (SCME), Jiangsu
National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University (NanjingTech),
30 South Puzhu Road, Nanjing 211816, P. R. China.
bDivision of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang
Technological University, Singapore 637371.
[email protected], [email protected]

Table of Contents

1. General information S2
2. General experimental procedure for the synthesis of -amino acetals and S2
spectroscopic information
3. Optimization study for the construction of aza-polycyclic frameworks via S8
Friedel-Crafts/Prins-type cyclization reaction
4. General experimental procedure for the construction of aza-polycyclic S10
frameworks with endo or exo-cyclic double bond and spectroscopic informatio

5. General experimental procedure for gram-scale reaction S18
6. Formal synthesis of homochelidonine and chelamidine S18
7. Reference S24
8. X-ray diffraction analysis S25
9. 1H and 13C NMR spectra S27

1
1. General Information
All reactions were carried out without exclusion of air or moisture unless otherwise stated.
Molecular iodine, sodium percarbonate (avail. H O 20-30%), and
2 2
trifluoromethanesulfonic acid were purchased from commercial suppliers, and used
directly as received. Commercial solvents and reagents were used without further
purification. Secondary amines1-4 and aldehydes5-8 were synthesized according to the
literatures. Reactions were monitored through thin layer chromatography [Merck 60 F254
precoated silica gel plate (0.2 mm thickness)]. Subsequent to elution, spots were visualized
using UV radiation (254 nm) on Spectroline Model ENF-24061/F 254 nm. Further
visualization was possible using basic solution of potassium permanganate or acidic
solution of ceric molybdate as stain, followed by heating on a hot plate. Flash
chromatography was performed using Merck silica gel 60 with distilled solvents. Infrared
spectra were recorded on a Shimadzu IR Prestige-21 FT-IR. Liquid samples were
examined as film between NaCl salt plates. HRMS spectra were recorded on a Waters Q-
Tof Permier Spectrometer. 1H NMR and 13C NMR spectra were recorded using Bruker
Avance 400 and 500 MHz spectrometers. Chemical shifts for 1H NMR spectra are
reported as δ in units of parts per million (ppm) downfield from SiMe (δ 0.0) and relative
4
to the signal of chloroform-d (δ 7.260, singlet). Multiplicities were given as: s (singlet);
brs (broad singlet); d (doublet); t (triplet); q (quartet); dd (doublets of doublet); ddd
(doublets of doublets of doublet); td (triplet of doublet); m (multiplets); ddt (doublet of
doublet of triplet) and etc. Coupling constants are reported as a J value in Hz. Carbon
nuclear magnetic resonance spectra (13C NMR) are reported as δ in units of parts per
million (ppm) downfield from SiMe (δ 0.0) and relative to the signal of chloroform-d (δ
4
77.00, triplet).

2. General Experimental Procedure for the Synthesis of -Amino Acetals9-10 and
Spectroscopic Information
Iodine (25 mg, 0.1 mmol) was added to a mixture of sodium percarbonate (79 mg, 0.5
mmol), secondary amines (0.5 mmol), and aldehydes (0.60 mmol) in methanol (0.5
mL)/1,2-dichloroethane (2.0 mL) at room temperature. The mixture was stirred at 40 °C
until secondary amine was completely converted by TLC detection. The resulting reaction
mixture was mixed with a small amount of silica gel and concentrated. The crude product
was purified by flash column chromatography (silica gel; ethyl acetate or diethyl
ether/hexane = 1:100, v/v) to afford the corresponding desired product.

N-allyl-N-(1,1-dimethoxy-4-phenylbutan-2-yl)-3-methylbut-2-en-1-amine (1a):
2
Light yellow oil; R = 0.59 (hexane: ethyl acetate = 5:1); 1H NMR (CDCl 400 MHz) δ
f 3,
7.27-7.12 (m, 5H), 5.85-5.76 (m, 1H), 5.19-5.03 (m, 3H), 4.27 (d, J = 5.39 Hz, 1H), 3.34
(s, 3H), 3.33 (s, 3H), 3.33-3.27 (m, 1H), 3.19-3.09 (m, 3H), 2.85-2.76 (m, 2H), 2.64-2.56
(m, 1H), 1.83-1.65 (m, 2H), 1.70 (s, 3H), 1.62 (s, 3H) ppm; 13C NMR (CDCl , 100 MHz)
3
δ 143.1, 138.4, 133.4, 128.5 (CH x 2), 128.1 (CH x 2), 125.4, 123.8, 115.6, 107.0, 58.6,
54.6, 54.4, 53.3, 48.0, 33.3, 28.6, 25.8, 17.9 ppm; HRMS (ESI, m/z): calcd for
C H NO + [M+H]+ 318.2433, found: 318.2436.
20 32 2

N-allyl-N-(1,1-dimethoxy-4-(o-tolyl)butan-2-yl)-3-methylbut-2-en-1-amine (1b):

Light yellow oil; R = 0.59 (hexane: ethyl acetate = 5:1); 1H NMR (CDCl 400 MHz) δ
f 3,
7.18-7.06 (m, 4H), 5.89-5.79 (m, 1H), 5.23-5.06 (m, 3H), 4.31 (d, J = 5.50 Hz, 1H), 3.38
(s, 3H), 3.37 (s, 3H), 3.34-3.29 (m, 1H), 3.22-3.13 (m, 3H), 2.91-2.79 (m, 2H), 2.61-2.53
(m, 1H), 2.33 (s, 3H), 1.76-1.59 (m, 8H) ppm; 13C NMR (CDCl , 100 MHz) δ 141.4,
3
138.4, 135.9, 133.6, 130.0, 128.8, 125.8, 125.6, 123.8, 115.8, 107.1, 59.2, 54.6, 54.5, 53.4,
48.0, 31.1, 27.5, 25.9, 19.3, 18.0 ppm; HRMS (ESI, m/z): calcd for C H NO + [M+H]+
21 34 2
332.2590, found: 332.2586.

N-allyl-N-(1,1-dimethoxy-4-(4-methoxyphenyl)butan-2-yl)-3-methylbut-2-en-1-amine
(1c):

3
Light yellow oil; R = 0.51 (hexane: ethyl acetate = 5:1); 1H NMR (CDCl 400 MHz) δ
f 3,
7.12 (d, J = 8.40 Hz, 2H), 6.81 (d, J = 8.45 Hz, 2H), 5.86-5.76 (m, 1H), 5.18-5.03 (m, 3H),
4.27 (d, J = 5.39 Hz, 1H), 3.77 (s, 3H), 3.34 (s, 3H), 3.33 (s, 3H), 3.32-3.27 (m, 1H), 3.19-
3.09 (m, 3H), 2.83-2.71 (m, 2H), 2.59-2.51 (m, 1H), 1.79-1.62 (m, 8H) ppm; 13C NMR
(CDCl , 100 MHz) δ 157.5, 138.4, 135.2, 133.4, 129.4 (CH x 2), 123.9, 115.6, 113.6 (CH
3
x 2), 107.1, 58.6, 55.2, 54.6, 54.4, 53.4, 48.1, 32.3, 28.9, 25.9, 17.9 ppm; HRMS (ESI,
m/z): calcd for C H NO + [M+H]+ 348.2539, found: 348.2537.
21 34 3

N-allyl-N-(1,1-dimethoxy-4-(thiophen-3-yl)butan-2-yl)-3-methylbut-2-en-1-amine
(1d):

Light yellow oil; R = 0.59 (hexane: ethyl acetate = 5:1); 1H NMR (CDCl 400 MHz) δ
f 3,
7.23-7.21 (m, 1H), 6.97-6.95 (m, 2H), 5.85-5.75 (m, 1H), 5.17-5.04 (m, 3H), 4.30 (d, J =
5.31 Hz, 1H), 3.36 (s, 3H), 3.35 (s, 3H), 3.34-3.29 (m, 1H), 3.20-3.09 (m, 3H), 2.86-2.79
(m, 2H), 2.70-2.62 (m, 1H), 1.85-1.67 (m, 5H), 1.63 (s, 3H) ppm; 13C NMR (CDCl , 100
3
MHz) δ 143.4, 138.4, 133.5, 128.4, 124.8, 123.8, 123.8, 119.8, 115.6, 106.9, 58.5, 54.7,
54.3, 53.3, 48.0, 27.6, 27.5, 25.9, 17.9 ppm; HRMS (ESI, m/z): calcd for C H NO S+
18 30 2
[M+H]+ 324.1997, found: 324.1992.

N-allyl-N-(3-(1-benzyl-1H-indol-3-yl)-1,1-dimethoxypropan-2-yl)-3-methylbut-2-en-
1-amine (1e):

Light yellow oil; R = 0.44 (hexane: ethyl acetate = 5:1); 1H NMR (CDCl 400 MHz) δ
f 3,
7.62 (d, J = 7.71 Hz, 1H), 7.28-7.20 (m, 4H), 7.15-7.05 (m, 4H), 6.99 (m, 1H), 5.71-5.61
(m, 1H), 5.26 (s, 2H), 5.02-4.90 (m, 3H), 4.33 (d, J = 5.39 Hz, 1H), 3.38 (s, 6H), 3.29-3.13
(m, 5H), 3.00-2.85 (m, 2H), 1.56 (s, 3H), 1.47 (s, 3H) ppm; 13C NMR (CDCl , 100 MHz)
3
4
δ 138.5, 138.0, 136.4, 133.2, 128.60 (CH x 2), 128.57, 127.4, 126.8, 126.7 (CH x 2), 123.9,
121.3, 119.3, 118.6, 115.5, 114.0, 109.3, 107.2, 59.8, 54.9, 54.6, 53.6, 49.7, 48.2, 25.7,
22.0, 17.8 ppm; HRMS (ESI, m/z): calcd for C H N O + [M+H]+ 433.2855, found:
28 37 2 2
433.2856.

N-allyl-N-cinnamyl-1,1-dimethoxy-4-phenylbutan-2-amine (1f):

Light yellow oil; R = 0.64 (hexane: ethyl acetate = 5:1); 1H NMR (CDCl 400 MHz) δ
f 3,
7.36-7.19 (m, 9H), 7.17-7.13 (m, 1H), 6.46 (d, J = 15.89 Hz, 1H), 6.21-6.13 (m, 1H), 5.88-
5.78 (m, 1H), 5.17 (d, J = 17.17 Hz, 1H), 5.07 (d, J = 10.16 Hz, 1H), 4.31 (d, J = 5.33 Hz,
1H), 3.48-3.31 (m, 9H), 3.23-3.18 (m, 1H), 2.90-2.82 (m, 2H), 2.67-2.59 (m, 1H), 1.87-
1.69 (m, 2H) ppm; 13C NMR (CDCl , 100 MHz) δ 143.0, 138.0, 137.4, 131.2, 129.9,
3
128.54 (CH x 2), 128.47 (CH x 2), 128.2 (CH x 2), 127.1, 126.2 (CH x 2), 125.5, 116.1,
107.1, 59.0, 54.8, 54.6, 53.6, 53.0, 33.3, 28.8 ppm; HRMS (ESI, m/z): calcd for
C H NO + [M+H]+ 366.2433, found: 366.2431.
24 32 2

N-allyl-1,1-dimethoxy-4-phenyl-N-(2-phenylallyl)butan-2-amine (1g):

Light yellow oil; R = 0.60 (hexane: ethyl acetate = 5:1); 1H NMR (CDCl 400 MHz) δ
f 3,
7.43 (d, J = 7.83 Hz, 2H), 7.32-7.12 (m, 6H), 7.07 (d, J = 7.61 Hz, 2H), 5.82-5.72 (m, 1H),
5.35 (d, J = 29.55 Hz, 2H), 5.13 (d, J = 17.16 Hz, 1H), 5.06 (d, J = 9.83 Hz, 1H), 4.26 (d,
J = 5.00 Hz, 1H), 3.67 (AB , J = 14.52 Hz, 2H), 3.36-3.30 (m, 7H), 3.20-3.14 (m, 1H),
q
2.88-2.84 (m, 1H), 2.58-2.50 (m, 1H), 2.31-2.23 (m, 1H), 1.80-1.60 (m, 2H) ppm; 13C
NMR (CDCl , 100 MHz) δ 146.9, 143.2, 140.6, 137.9, 128.4 (CH x 2), 128.1 (CH x 2),
3
128.0 (CH x 2), 127.3, 126.8 (CH x 2), 125.4, 116.5, 114.8, 107.3, 58.7, 54.97, 54.94, 54.7,
5
53.4, 33.1, 28.4 ppm; HRMS (ESI, m/z): calcd for C H NO + [M+H]+ 366.2433, found:
24 32 2
366.2432.

N-allyl-1,1-dimethoxy-N-(2-phenylallyl)-4-(o-tolyl)butan-2-amine (1h):

Light yellow oil; R = 0.71 (hexane: ethyl acetate = 5:1); 1H NMR (CDCl 400 MHz) δ
f 3,
7.43 (d, J = 7.51 Hz, 2H), 7.30-7.20 (m, 3H), 7.08-7.01 (m, 4H), 5.86-5.76 (m, 1H), 5.37
(d, J = 30.08 Hz, 2H), 5.16 (d, J = 17.17 Hz, 1H), 5.09 (d, J = 10.10 Hz, 1H), 4.27 (d, J =
5.15 Hz, 1H), 3.69 (AB , J = 14.50 Hz, 2H), 3.38-3.30 (m, 7H), 3.19-3.13 (m, 1H), 2.94-
q
2.89 (m, 1H), 2.54-2.46 (m, 1H), 2.26-2.17 (m, 1H), 2.15 (s, 3H), 1.72-1.53 (m, 2H) ppm;
13C NMR (CDCl , 100 MHz) δ 146.8, 141.4, 140.5, 137.8, 135.8, 129.9, 128.5, 127.9
3
(CH x 2), 127.3, 126.7 (CH x 2), 125.7, 125.5, 116.5, 114.9, 107.1, 58.9, 55.0, 54.9, 54.7,
53.2, 30.7, 27.3, 19.2 ppm; HRMS (ESI, m/z): calcd for C H NO + [M+H]+ 380.2590,
25 34 2
found: 380.2583.

N-allyl-1,1-dimethoxy-4-(4-methoxyphenyl)-N-(2-phenylallyl)butan-2-amine (1i):

Light yellow oil; R = 0.62 (hexane: ethyl acetate = 5:1); 1H NMR (CDCl 400 MHz) δ
f 3,
7.42 (d, J = 7.25 Hz, 2H), 7.32-7.22 (m, 3H), 6.98 (d, J = 8.48 Hz, 2H), 6.77 (d, J = 8.47
Hz, 2H), 5.82-5.71 (m, 1H), 5.35 (d, J = 27.84 Hz, 2H), 5.12 (d, J = 17.00 Hz, 1H), 5.06 (d,
J = 10.10 Hz, 1H), 4.25 (d, J = 5.04 Hz, 1H), 3.75 (s, 3H), 3.66 (AB , J = 14.56 Hz, 2H),
q
3.35-3.31 (m, 7H), 3.20-3.15 (m, 1H), 2.87-2.82 (m, 1H), 2.52-2.45 (m, 1H), 2.27-2.19 (m,
1H), 1.77-1.57 (m, 2H) ppm; 13C NMR (CDCl , 100 MHz) δ 157.5, 146.9, 140.6, 137.9,
3
135.2, 129.2 (CH x 2), 127.9 (CH x 2), 127.3, 126.7 (CH x 2), 116.4, 114.8, 113.5 (CH x
2), 107.3, 58.6, 55.2, 54.9 (CH x 1), 54.9 (CH x 1), 54.7, 53.4, 32.2, 28.6 ppm; HRMS
2 3
(ESI, m/z): calcd for C H NO + [M+H]+ 396.2539, found: 396.2541.
25 34 3
6
N-allyl-1,1-dimethoxy-4-(naphthalen-2-yl)-N-(2-phenylallyl)butan-2-amine (1j):

Light yellow oil; R = 0.60 (hexane: ethyl acetate = 10:1); 1H NMR (CDCl 400 MHz) δ
f 3,
7.80 – 7.71 (m, 3H), 7.51 (s, 1H), 7.48-7.37 (m, 4H), 7.36-7.27 (m, 3H), 7.26-7.20 (m, 1H),
5.90 – 5.71 (m, 1H), 5.41-5.33 (m, 2H), 5.18-5.06 (m, 2H), 4.31 (dd, J = 5.0, 1.8 Hz, 1H),
3.93 – 3.52 (m, 2H), 3.46 – 3.31 (m, 7H), 3.26 – 3.11 (m, 1H), 2.96-2.90 (m, 1H), 2.74-
2.66 (m, 1H), 2.55 – 2.36 (m, 1H), 1.96 – 1.68 (m, 2H); 13C NMR (CDCl , 100 MHz) δ
3
146.97, 140.76, 140.69, 138.00, 133.68, 131.92, 128.13, 127.95, 127.67, 127.49, 127.45,
126.90, 126.21, 125.81, 124.98, 116.71, 115.10, 107.23, 58.66, 55.18, 55.00, 54.85, 53.56,
33.30, 28.25 ppm; HRMS (ESI, m/z): calcd for C H NO + [M+H]+ 416.2590, found:
24 32 2
416.2586.

N-allyl-1,1-dimethoxy-N-(2-phenylallyl)-4-(thiophen-3-yl)butan-2-amine (1k):

Light yellow oil; R = 0.70 (hexane: ethyl acetate = 5:1); 1H NMR (CDCl 400 MHz) δ
f 3,
7.40 (d, J = 7.13 Hz, 2H), 7.31-7.24 (m, 3H), 7.18-7.16 (m, 1H), 6.82-6.80 (m, 2H), 5.79-
5.69 (m, 1H), 5.33 (d, J = 33.03 Hz, 2H), 5.12 (d, J = 17.18 Hz, 1H), 5.05 (d, J = 10.11 Hz,
1H), 4.26 (d, J = 4.94 Hz, 1H), 3.65 (AB , J = 14.49 Hz, 2H), 3.34-3.30 (m, 7H), 3.18-
q
3.13 (m, 1H), 2.87-2.82 (m, 1H), 2.56-2.48 (m, 1H), 2.32-2.24 (m, 1H), 1.81-1.62 (m, 2H)
ppm; 13C NMR (CDCl , 100 MHz) δ 146.9, 143.3, 140.6, 137.8, 128.3, 127.9 (CH x 2),
3
127.3, 126.7 (CH x 2), 124.7, 119.5, 116.4, 114.8, 107.1, 58.4, 55.0, 54.9, 54.6, 53.4, 27.4,
27.2 ppm; HRMS (ESI, m/z): calcd for C H NO S+ [M+H]+ 372.1997, found: 372.1998.
22 30 2

N-allyl-4-(1-benzyl-1H-indol-3-yl)-1,1-dimethoxy-N-(2-phenylallyl)butan-2-amine (1l):
7
Light yellow oil; R = 0.60 (hexane: ethyl acetate = 5:1); 1H NMR (CDCl 400 MHz) δ
f 3,
7.48 (d, J = 7.80 Hz, 1H), 7.44-7.41 (m, 2H), 7.30-7.04 (m, 11H), 6.79 (s, 1H), 5.83-5.73
(m, 1H), 5.34 (d, J = 26.11 Hz, 2H), 5.20 (s, 2H), 5.11 (d, J = 17.28 Hz, 1H), 5.03 (d, J =
10.28 Hz, 1H), 4.28 (d, J = 5.01 Hz, 1H), 3.68 (AB , J = 14.51 Hz, 2H), 3.38-3.33 (m, 4H),
q
3.31 (s, 3H), 3.20-3.15 (m, 1H), 2.98-2.93 (m, 1H), 2.73-2.66 (m, 1H), 2.46-2.35 (m, 1H),
1.90-1.73 (m, 2H) ppm; 13C NMR (CDCl , 100 MHz) δ 146.9, 140.6, 138.0, 137.9, 136.6,
3
128.6 (CH x 2), 128.3, 128.0 (CH x 2), 127.4, 127.3, 126.8 (CH x 2), 126.7 (CH x 2),
125.1, 121.4, 119.3, 118.5, 116.5, 116.4, 114.8, 109.3, 107.3, 58.7, 54.98, 54.94, 54.6,
53.4, 49.7, 26.8, 22.4 ppm; HRMS (ESI, m/z): calcd for C H N O + [M+H]+ 495.3012,
33 39 2 2
found: 495.3008.

N-allyl-1,1-dimethoxy-N-(2-methylallyl)-4-phenylbutan-2-amine (1m):

Light yellow oil; R = 0.75 (hexane: ethyl acetate = 5:1); 1H NMR (CDCl 400 MHz) δ
f 3,
7.27-7.13 (m, 5H), 5.84-5.74 (m, 1H), 5.12 (d, J = 17.19 Hz, 1H), 5.04 (d, J = 10.10 Hz,
1H), 4.86 (d, J = 30.56 Hz, 2H), 4.28 (d, J = 5.02 Hz, 1H), 3.35 (s, 6H), 3.27-3.03 (m, 4H),
2.90-2.82 (m, 2H), 2.62-2.55 (m, 1H), 1.85-1.64 (m, 5H) ppm; 13C NMR (CDCl , 100
3
MHz) δ 144.6, 143.1, 138.1, 128.4 (CH x 2), 128.2 (CH x 2), 125.5, 116.1, 112.3, 107.0,
58.6, 56.8, 54.74, 54.65, 53.6, 33.5, 28.7, 20.6 ppm; HRMS (ESI, m/z): calcd for
C H NO + [M+H]+ 304.2277, found: 304.2276.
19 30 2

3. Optimization Study for the Construction of Aza-Polycyclic Frameworks via
Friedel-Crafts/Prins-type Cyclization Reaction
An optimization study was performed using the α-amino acetal 1a as the model substrate
to examine various reaction conditions. The reaction of the α-amino acetal 1a without any
8
additive at 20 oC in dichloromethane did not afford any desired products after a 24 hour
reaction time (Table S1, entry 1). This confirmed that the reaction could not proceed in the
absence of Lewis or Brønsted acids. Various Lewis acids (AlCl , FeCl , and BF .OEt ) and
3 3 3 2
Brønsted acids such as trifluoroacetic acid (TFA) and trifluoromethanesulfonic acid
(TfOH) were then tested for this reaction. It was observed that TfOH was the most
efficient additive, affording the desired product 2a in 93% yield (Table S1, entries 2-6).
After solvent screening (Table S1, entries 6-8), dichloromethane (DCM) was found to be
the suitable solvent, furnishing the desired product 2a in 93% yield at 20 oC. Under similar
conditions, the use of acetonitrile did not afford any desired product, while nitromethane
gave the product in a lower yield (80%). Gratifyingly, the different products 2a or 3a
could be obtained in excellent or good yield by adjusting the stoichiometry of TfOH
(Table S1). When 1.0 equivalent of TfOH was used, the yield of 2a was significantly
decreased (Table S1, entry 9). It was ascertained that when the amount of TfOH was
increased to 4.0 and even 6.0 equivalents, the yield of 3a could be increased to 81% (Table
S1, entries 10-11).

Table S1. Optimization study on Friedel-Crafts/Prins-type cyclization reactiona

9
aUnless otherwise noted, the reactions were carried out using α-amino acetal 1a (0.1 mmol,
1.0 equiv.), additive (2.0 equiv.), solvent (1.0 mL). bIsolated yields based on α-amino
acetal 1a. All = allyl.
In a word, after our initial optimization studies, trifluoromethanesulfonic acid (TfOH)
was identified as the optimal mediator for intramolecular Friedel-Crafts/Prins-type
cyclization reaction of α-amino acetals at 20 oC in DCM, with the use of 2.0 equivalents
for the selective formation of product 2a in 93% yield and 6.0 equivalents for the
formation of product 3a in 81% yield.

4. General Experimental Procedure for the Construction of Aza-Polycyclic
Frameworks with endo or exo-Cyclic Double Bond and Spectroscopic Information
Typical procedure for intramolecular Friedel-Crafts/Prins-type cyclization reaction of α-
amino acetals (N-allyl-N-(1,1-dimethoxy-4-phenylbutan-2-yl)-3-methylbut-2-en-1-amine
1a as a model substrate): Trifluoromethanesulfonic acid (30 mg, 0.2 mmol, 2.0 equiv.) was
added to -amino acetal 1a (31.7 mg, 0.1 mmol, 1.0 equiv.) in dry dichloromethane (1.0
ml) at 20 oC and was stirred at 20 oC for the specified time. The reaction mixture was
quenched with saturated aqueous sodium bicarbonate (NaHCO ). The aqueous layer was
3
extracted with dichloromethane (2.0 ml × 3) and the combined organic layers were washed
with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure.
The crude oil was redissolved in a minimum amount of dichloromethane and was purified
by flash column chromatography (silica gel; triethylamine/ethyl acetate/hexane = 0.1:1:10)
to afford the desired product 2a as the light yellow oil (23.6 mg, 93%). Then the product
2a was dissolved in dichloromethane, hexane was added into it and solvent was
evaporated to obtain the crystal (CCDC 965133).

3-allyl-1-(propan-2-ylidene)-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indole (2a):

10