An extension of nickel-catalyzed reductive coupling between tertiary alkyl halides with allylic carbonates

Article abstract of DOI:10.1016/j.tet.2018.07.057

The nickel catalyzed reductive coupling of allylic carbonates with chloro-cyclotryptamine analogs to construct sterically congested all C(sp³) quaternary centers has been achieved with emphasis on the substrate scope. And the using of dienyl me

Full text of DOI:10.1016/j.tet.2018.07.057

Accepted Manuscript
An extension of nickel-catalyzed reductive coupling between tertiary alkyl halides with
allylic carbonates
Yingying Yu, Haifeng Chen, Qun Qian, Ken Yao, Hegui Gong
PII:
S0040-4020(18)30923-2
10.1016/j.tet.2018.07.057
TET 29717
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 11 May 2018
Revised Date: 20 July 2018
Accepted Date: 28 July 2018
Please cite this article as: Yu Y, Chen H, Qian Q, Yao K, Gong H, An extension of nickel-catalyzed
reductive coupling between tertiary alkyl halides with allylic carbonates, Tetrahedron (2018), doi:
10.1016/j.tet.2018.07.057.
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ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
An extension of nickel-catalyzed reductive coupling between tertiary alkyl
halides with allylic carbonates
Yingying Yua, Haifeng Chenb, Qun Qian*a, Ken Yao*a, Hegui Gong*a, b
a Department of Chemistry, Shanghai University 99 Shang-Da Road, Shanghai 200444, China.
b School of Materials Science and Engineering, Shanghai University
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The nickel catalyzed reductive coupling of allylic carbonates with chloro-cyclotryptamine
analogs to construct sterically congested all C(sp3) quaternary centers has been achieved with
emphasis on the substrate scope. And the using of dienyl methyleneyl carbonates coupling with
a variety of tertiary alkyl halides furnished the dienylated products improved the reaction’s
applicability.
Available online
2017 Elsevier Ltd. All rights reserved
.
Keywords:
Allylation
Chloro-cyclotryptamine
Nickel catalyzed
Extension
Dienyl carbonate
1. Introduction
The challenges in the construction of all C(sp3) carbon
quaternary stereogenic centers have evoked a number of
synthetic strategies based on transition-metal-catalyzed
conventional coupling of organometallic reagents with suitable
[1-4]
electrophiles.
Among them, Cu-catalyzed Kumada assembly
of tertiary alkyl-Grignard nucleophiles with alkyl electrophiles is
[1]
of note.
The reactions display excellent compatibility with
unactivated alkyl groups, although the functional group tolerance
is constrained due to the use of alkyl-MgX reagents. The
coupling of tertiary alkyl nucleophiles with allylic electrophiles
[2]
has also been examined.
The allylation process often suffers
Scheme 1. Cross-coupling strategies for the construction of allyl
from poor regioselective issues due to the competitive formation
of α and γ products. Using allyl and benzyl zinc or magnesium as
the nucleophiles, Oshima demonstrated the viability of formation
containing all C (sp3) quaternary carbon centers
Recently, we disclosed a Ni-catalyzed reductive coupling of
of all carbon quaternary centers by their coupling with
[5]
tertiary alkyl halides with allylic carbonates,
which allows
[3]
unactivated tertiary alkyl halides.
With Ag- or Co-catalysts,
efficient preparation of all carbon quaternary congested centers
constituting four C(sp3)-C(sp3) bonds. The mild reaction enables
a wide set of unactivated tertiary alkyl halides and allylic
carbonates with aryl- or alkyl-substitutes. Different substitution
patterns were investigated. For 1- or 3-substituted alkyl or aryl
allylic carbonates, the coupling results always favor the addition
of tertiary alkyl group to the less hindered allylic carbon centers.
this coupling protocol also results in a mixture of α and γ
isomers, when a 1- and/or 3-substituted allylic carbonate was
[3c]
subjected to the reaction conditions.
When both allyl
nucleophiles and allyl electrophiles are employed, excellent
regioselectivities were observed in a Pd-catalyzed allyl-allyl
coupling method, wherein the coupling of allyl-B(pin) with
internal allyl electrophiles produces the quaternary centers when
3,3’-disubstituted allylic acetates were utilized (Scheme 1). [4]
In this paper, we wish to provide more detailed studies on
the reductive allylation method, with emphasis on the substrate
scope. Firstly, we investigated the allylation of potential bio-
activated cyclotryptamine structure. Then, we expanded the
substrate scope to penta-dienyl carbonates.
Corresponding authors. Fax: +86 21 66134594; e-mail addresses:
qianqun@shu.edu.cn, hegui_gong@shu.edu.cn,
yao850618@gmail.com.

2
Tetrahedron
2. Results and Discussion
Table 1. Optimization for the coupling of 2-phenylallyl
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carbonate with chloro-cyclotryptamine 1
.
(1) The coupling of chloro-cyclotryptamine derivatives
Cyclotryptamine derivatives are an important scaffold that can
be found in a diverse set of natural products, alkaloids and
pharmaceuticals. [6-8] The examples include bioactive compounds
flustramine
channels,
B
which blocks voltage-activated potassium
[6]
Fructigenine A which displays growth-inhibitory
activity against Avena coleoptile and anti-inflammatory activity
[7]
and 5-N-acetylardeemin which is one of the most efficient
inhibitors of multidrug resistance (MDR) toantitumor agents such
as vinblastine, taxol, and doxorubicin (Figure 1). [7b, 8]
Entry
Variation from the condition A
Yield[b]
66%[c]
trace
57%
8%
1
2
none
no Ni
3
no pyridine
no ligand
no MgCl2
no Zn
4
5
32%
ND
6
7
Ni(COD)2
Ni(diglyme)
NiI2
60%
58%
63%
trace
12%
8
9
10
11
L5 instead of L1
L8 instead of L1
[a] Standard conditions: 1 (0.15mmol), allylic carbonate 2a (2 equiv), Ni
(10%), ligand (15%), pyridine (30%), MgCl2 (100%), Zn (300%), DMA (1
mL), 25oC. [b] NMR yield using 2,5-dimethylfuran as the internal reference.
[c] Yield of isolate yield. COD=1,5-cycloocatadiene, DMA= N, N-
dimethylacetamide.
Figure 1. Examples of naturally-occurring products containing
cyclotryptamine scaffold.
In our previous studies, we have showcased that use of Boc-
protected chloro-cyclotryptamine precursor
1
effectively
provided the allylated pyrroloindoline 3a in 66% yield by
coupling with 2-phenylallyl carbonate 2a. Compound 3a can be
viewed as an analog of the natural products described in Figure 1.
Such a result prompted us to quest the generality of the allylation
reaction conditions, however, no improvement was attained
(method A, Table 1.).
our delight, a chloro-substrate contacting a tetrahydrofuran ring
was also competent, which offered 12 has 47% yield. This
product can be viewed as a key scaffold for nature-occurring
Physovenine (Figure 1). Finally, the more complex chloro-
substrates derived from tryptophan were also examined, which
gave 13 in 56% yield.
With the standard method A in hand, a number of 2-aryl allylic
carbonates substituted with both electron-withdrawing and
electron-donating groups on the aryl moieties were first explored.
Good yields were obtained for 3b-f regardless of the substitution
patterns (Figure 2). By comparison, the unsubstituted allylic
carbonate furnished 3g in a moderate yield. Whereas 2-methyl-
decorated allyl carbonate was much less effective, generating 3h
in 42% yield, the branched but-3-en-2-yl methyl carbonate
delivered 3i in 48% yield by addition of the tertiary alkyl group
to the 1-position of the allyl substrate; product 3i was also
contaminated with a branched isomer with a 10:1 linear/branched
ratio. Notably, for 1-methyl-substitted allylic carbonate, no
appreciable coupling yield was observed.
(2) The coupling with penta-dienyl carbonates
Next, a variety of chloro-cyclotryptamine analogs of 1 were
investigated for the methyl (2-aryl) allyl carbonates 2a, which
generated 4-13 in moderate to good yields. The chloro-substrates
beating 5-methoxy and Cl gave 4-5 in preparatively useful yields.
Different protecting groups on the nitrogen atoms of the chloro-
substrates other than Boc- were effective. These include Cbz,
Methoxycarbonyl and Tosyl as manifested in the example of 6-
10. More interestingly, a methyl substituent at C (2a)-position of
the chloro-substrate delivered 11 in 45% yield which is
composed of two consecutive quaternary carbon centers. To
Scheme 2. The optimal reaction conditions for 14.

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Figure 2. Substrate scope. [a] ph-pybox (L2, 15%) was used, no enantioselectivity was observed. [b] Standard conditions except
that Ni (COD)2 (10%), di-tbu-bipyridine (L5, 15%), 2,6-diamine-pyridine (30%) was used. [c] but-3-en-2-yl methyl carbonate
was used, 10:1 ratio of linear/branched. [d] NiBr2(diglyme) (10%), 4,7-dimethoxy-2,9-dimethyl-1,10-phenanthroline (L7, 15%),
2,6-diamine-pyridine (30%), MgBr2 (100%), Mn (300%) was used.
product 25 in 52% yield (equation 1). However, the reaction is
not efficient for allyl substrates that bear two or more substituents
may due to the steric hindrance.
To further expand the scope of the substrates, we explored the
coupling of (E)-methyl penta-2,4-dien-1-yl carbonate with
different tertiary alkyl halides. With ligand L7, a good yield was
obtained for 14 (method B, Scheme 2). Extension the method B
to other tertiary bromide generated 15-24 generally in moderate
to good yields (Figure 3). The reaction conditions displayed
excellent functional group tolerance even for a free phenolic
group as evident in 17. Similar to our previous findings, the
primary bromide and tosylate were tolerated as in the products
19-20, which provide a possibility of further transformations of
these functional groups. In addition, the reaction also
accommodates the chloro-cyclotryptamine derivatives which
produced the dienyl products 21-24 in moderate yields.
Equation 1. Coupling of methyl 1-bromocyclopropane-1-
carboxylate with 2a
3. Conclusions
In summary, an extension of nickel-catalyzed reductive
coupling between tertiary alkyl halides with allylic carbonates to
generate highly sterically congested all C(sp3) quaternary centers
is illustrated. We have developed the strategy of reductive
allylation for chloro-cyclotryptamine derivatives, which is
suitable for a variety of aryl and alkyl-substituted allylic
carbonates and a number of chloro-cyclotryptamine analogs with
different protecting groups. Installation of 1,3-dienyl methylenyl
groups to the C3a-positions of the cyclotryptamine derivatives is
also competent. In addition, penta-dienyl carbonate can
efficiently coupling with tertiary alkyl halides. All these
expansion, shows the potential value of this reaction.
4. Experimental section
4.1. General Information
Experiments were conducted under a nitrogen atmosphere in
oven-dried or flame-dried glassware with magnetic stirring,
unless otherwise specified. For product purification by flash
column chromatography, silica gel (300−400 mesh) and
petroleum ether (bp 60−90 °C) were used. NMR spectra were
measured on a Bruker 600 MHz and a Bruker 500 MHz NMR
instrument at room temperature. Reference peaks for chloroform
Figure 3. Substrate scope for the coupling of dienyl mehtylenyl
carbonates
(3) The coupling of other substrates
With further investigation of the substrate scopes of the
allylation event, we found that activated tertiary alkyl halides are
also suitable for this protocol. For instance, the coupling of
methyl 1-bromocyclopropane-1-carboxylate with 2a furnished
1
in H NMR and 13C NMR spectra were set at 7.26 ppm and 77.0
ppm, respectively. High-resolution mass spectra (HRMS) were
obtained using a IonSpec 4.7 TESLA FTMS. Melting point was

4
Tetrahedron
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recorded on a micro melting point apparatus (X-4, YUHUA
13.9 Hz, 1H), 2.76-2.71 (m, 1H), 1.93-1.85 (m, 2H), 1.58 (s, 9H),
Co., Ltd, Gongyi, China). IR spectra was detected by AVATAR
1.46 (s, 9H). 13C NMR (150 MHz, Chloroform-d): δ 163.3,
161.6, 153.8, 152.1, 144.3, 144.2, 144.0, 142.7, 129.5, 129.4,
128.1, 123.4, 122.6, 121.9, 118.5, 113.9, 113.8, 113.3, 113.1,
81.1, 79.6, 56.6, 53.3, 45.8, 43.3, 28.3, 28.2. 19F NMR (564
MHz, Chloroform-d): δ 113.6. HRMS (ESI) exact mass
calculated for [M+H+] (C29H36FN2O4): m/z 495.2654; found:
495.2660.
370 FT-IR and recorded in wave number, cm-1.
4.1.1 General Method A
To a flame-dried Schlenk tube equipped with a stir bar was
loaded zinc power (58.8 mg, 0.9 mmol, 300 mol %), followed by
addition of MgCl2 (28.6 mg, 0.3 mmol, 100 mol %), iPr-box L1
(13.6 mg, 0.045 mmol, 15 mol %), NiBr2ꢀglyme (9.2 mg, 0.03
mmol, 10 mol %). The tube was evacuated and refilled nitrogen
(N2) three time. DMA (1.0 mL) was added via syringe, followed
by addition of chloro-cyclotryptamine/tertiary bromide (0.3
mmol, 100%), Allylic Carbonates (0.6 mmol, 200 mol %),
Pyridine (0.09 mmol, 30 mol %). After the reaction mixture was
allowed to stir for 12 hours under N2 atmosphere at 25oC. It was
loaded onto a silica column. Flash column chromatography
provided the product as oil or foam solid.
4.2.3
Di-tert-butyl3a-(2-(4-fluorophenyl)
allyl)-2,3,3a,8a-
tetrahydro pyrrolo[2,3-b] indole-1,8-dicarboxylate (3c)
According to method A, except L2 was used, flash column
chromatography (SiO2: 5% ethyl acetate in petroleum ether)
provided this compound in 75% yield (111.2 mg, 0.225 mmol) as
foam solid. mp: 102-104 C. The cis-structure was confirmed by
NOESY spectrum wherein the allylic CH2 protons correlate with
the proton on the carbon adjacent to the two nitrogen atoms.
o
4.1.2 General Method B
IR (KBr) νꢀ=ꢀ2973, 2928,1706, 1478, 1391, 1160, 894, 841, 751.
1H NMR (600 MHz, Chloroform-d): δ 7.50 (bs, 1H), 7.08 (t, J
= 7.5 Hz, 3H), 6.91-6.82 (m, 4H), 6.04 (s, 1H), 5.13 (s, 1H), 5.01
(s, 1H), 3.64 (dd, J = 11.4, 7.8 Hz, 1H), 3.00 (d, J = 13.8 Hz,
1H), 2.84 (d, J = 13.2 Hz, 1H), 2.74-2.70 (m, 1H), 1.91-1.83 (m,
2H), 1.56 (s, 9H), 1.46 (s, 9H). 13C NMR (150 MHz,
Chloroform-d): δ 162.7, 161.1, 153.7, 152.1, 144.1, 142.7,
137.9, 133.8, 127.9, 127.8, 123.3, 122.5, 117.6, 116.1, 114.8,
114.7, 81.0, 79.6, 56.5, 53.3, 45.7, 43.6, 28.3, 28.2. 19F NMR
(564 MHz, Chloroform-d): δ 115.3. HRMS (ESI) exact mass
calculated for [M+H+] (C29H36FN2O4): m/z 495.2654; found:
495.2686.
To a flame-dried Schlenk tube equipped with a stir bar was
loaded zinc power (58.8 mg, 0.9 mmol, 300 mol %), followed by
addition of MgCl2 (28.6 mg, 0.3 mmol, 100 mol %), L7 (12.1
mg, 0.045 mmol, 15 mol %), NiBr2ꢀglyme (9.2 mg, 0.03 mmol,
10 mol %). The tube was evacuated and refilled nitrogen (N2)
three time. DMA (1.0 mL) was added via syringe, followed by
addition of chloro-cyclotryptamine/tertiary bromide (0.3 mmol,
100%), Allylic Carbonates (0.6 mmol, 200 mol %), Pyridine
(0.09 mmol, 30 mol %). After the reaction mixture was allowed
to stir for 12 hours under N2 atmosphere at 25 oC. It was loaded
onto a silica column. Flash column chromatography provided the
product as oil or solid.
4.2.4 Di-tert-butyl (3aS)-3a-(2-(3-methoxyphenyl) allyl)-
2,3,3a,8a-tetrahydropyrrolo [2,3-b] indole-1,8-dicarboxylate
(3d)
4.2 Synthetic procedure and characterization data
4.2.1
Di-tert-butyl(3aS,8aR)-3a-(2-phenylallyl)-2,3,3a,8a-
According to method A, flash column chromatography (SiO2: 5%
ethyl acetate in petroleum ether) provided this compound in 70%
yield (106.3 mg, 0.210 mmol) as foam solid. mp: 87-89 oC.
tetrahydropyrrolo[2,3-b] indole-1,8-dicarboxylate (3a)
According to method A, flash column chromatography (SiO2: 5%
ethyl acetate in petroleum ether) provided this compound in 66%
yield (94.4 mg, 0.198 mmol) as foam solid. mp: 44-45 C. The
cis-structure was confirmed by NOESY spectrum wherein the
allylic CH2 protons correlate with the proton on the carbon
adjacent to the two nitrogen atoms.
IR (KBr) νꢀ=ꢀ2972, 2928, 1705, 1478, 1394, 1160, 891, 752. 1H
NMR (600 MHz, Chloroform-d): δ 7.53 (bs, 1H), 7.15 (t, J =
12.0 Hz, 1H), 7.10 (t, J = 12.0 Hz, 1H), 6.94 (d, J = 6.0 Hz, 1H),
6.85 (t, J = 12.0 Hz, 1H), 6.81 (d, J = 6.0 Hz, 1H), 6.74 (dd, J =
12.0, 6.0 Hz, 1H), 6.67 (s, 1H), 6.06 (s, 1H), 5.22 (s, 1H), 4.99 (s,
1H), 3.76 (s, 3H), 3.63-3.60 (m, 1H), 3.00 (d, J = 12.0 Hz, 1H),
2.84 (d, J = 12.0 Hz, 1H), 2.71 (q, J = 12.0 Hz, 1H), 1.86 (t, J =
6.0 Hz, 2H), 1.57 (s,9H), 1.45 (s, 9H). 13C NMR (150 MHz,
Chloroform-d): δ 159.2, 152.2, 144.8, 143.5, 142.6, 129.0,
127.9, 123.5, 122.6, 118.8, 117.7, 112.7, 112.0, 81.0, 79.8, 56.6,
55.0, 53.4, 45.9, 43.2, 28.3, 28.2. HRMS (ESI) exact mass
calculated for [M+H+] (C30H39N2O5): m/z 507.2853; found:
507.2831
o
1
IR (KBr) νꢀ=ꢀ2975, 2931, 1703, 1470, 1393, 1148, 864, 747. H
NMR (600 MHz, Chloroform-d): δ 7.51 (s, 1H), 7.24-7.18 (m,
5H), 7.10 (t, J = 7.5 Hz, 1H), 6.94 (d, J = 7.5 Hz, 1H), 6.84 (t, J =
7.5 Hz, 1H), 6.07 (s, 1H), 5.21 (s, 1H), 5.00 (s, 1H), 3.63-3.60
(m, 1H), 3.03 (d, J = 13.8 Hz, 1H), 2.86 (d, J = 13.8 Hz, 1H),
2.74-2.68 (m, 1H), 1.85-1.83 (m, 2H), 1.57 (s, 9H), 1.46 (s, 9H).
13C NMR (150 MHz, Chloroform-d): δ 153.8, 152.3, 145.0,
142.7, 142.0, 134.2, 128.1, 128.0, 127.2, 126.3, 123.5, 122.6,
117.7, 116.4, 81.0, 79.9, 56.6, 45.9, 43.2, 28.4, 28.3. HRMS
(APCI) exact mass calculated for [M+H+] (C29H37N2O4): m/z
477.2748; found: 477.2910.
4.2.5 Di-tert-butyl (3aS)-3a-(2-(4-methoxyphenyl) allyl)-
2,3,3a,8a-tetrahydropyrrolo [2,3-b] indole-1,8-dicarboxylate
(3e)
4.2.2
Di-tert-butyl(3aS)-3a-(2-(3-fluorophenyl)
allyl)-
According to method A, flash column chromatography (SiO2: 5%
ethyl acetate in petroleum ether) provided this compound in 69%
yield (104.8 mg, 0.207 mmol) as foam solid. mp: 78-79 oC.
2,3,3a,8a-tetrahy dropyrrolo [2,3-b] indole-1,8-dicarboxylate
(3b)
According to method A, flash column chromatography (SiO2: 5%
ethyl acetate in petroleum ether) provided this compound in 68%
yield (100.9 mg, 0.204 mmol) as foam solid. mp: 100-101 oC.
IR (KBr) νꢀ=ꢀ2972, 2929, 1704, 1476, 1390, 1158, 889, 750. 1H
NMR (600 MHz, Chloroform-d): δ 7.47 (bs, 1H), 7.14 (q, J =
6.0 Hz, 1H), 7.07 (t, J = 7.5 Hz, 1H), 6.90 (t, J = 7.0 Hz, 2H),
6.86-6.79 (m, 3H), 6.06 (s, 1H), 5.21 (s, 1H), 5.06 (s, 1H), 3.64
(q, J = 11.2, 7.2 Hz, 1H), 3.01 (d, J = 13.7 Hz, 1H), 2.83 (d, J =
IR (KBr) νꢀ=ꢀ2971, 2927, 1705, 1607, 1473, 1393, 1157, 1028,
892, 752. 1H NMR (600 MHz, Chloroform-d): δ 7.53 (bs, 1H),
7.14-7.10 (m, 3H), 6.95 (d, J = 6.0 Hz, 1H), 6.87 (t, J = 6.0 Hz,
1H), 6.76 (d, J = 6.0 Hz, 2H), 6.05 (s, 1H), 5.15 (s, 1H), 4.90 (s,
1H), 3.77 (s, 3H), 3.63-3.60 (m, 1H), 2.96 (d, J = 18.0 Hz, 1H),
2.82 (d, J = 18.0 Hz, 1H), 2.73-2.68 (m, 1H), 1.85-1.83 (m, 2H),
1.56 (s, 9H), 1.45 (s, 9H). 13C NMR (150 MHz, Chloroform-d):
δ 158.8, 153.8, 152.2, 144.2, 142.6, 134.3, 127.9, 127.4, 123.5,

122.5, 116.4, 113.5, 81.0, 79.8, 56.6, 55.1, 45.9, 43.1, 28.3, 28.2.
NiBr2ꢀdiglyme (10 mol %) and MgBr2 (100 mol %), Mn (300 mol
%) and L7 (15 mol %). Flash column chromatography (SiO2: 2%
ethyl acetate in petroleum ether) provided a mixture of linear and
branched isomer in overall 48% yield (59.7 mg, 0.144 mmol) as
foamy semisolid. The ratio of the linear to branched was
determined to be ~10:1 based on 1H NMR analysis.
ACCEPTED MANUSCRIPT
HRMS (ESI) exact mass calculated for [M+H+] (C30H39N2O5):
m/z 507.2853; found: 507.2839.
4.2.6
Di-tert-butyl(3aS)-3a-(2-(2-methoxyphenyl)
allyl)-
2,3,3a,8a-tetrahy dropyrrolo [2,3-b] indole-1,8-dicarboxylate
(3f)
IR (KBr) νꢀ=ꢀ2974, 2928, 1707, 1476, 1395, 1160, 892, 753. 1H
NMR (600 MHz, Chloroform-d): δ 7.57 (bs, 1H), 7.19 (t, J =
Hz, 1H), 7.09 (d, J = 12.0 Hz, 1H), 7.01 (t, J = 6.0 Hz, 1H), 6.01
(s, 1H), 5.49-5.46 (m, 1H), 5.25-5.20 (m, 1H), 3.73 (t, J = 10.8,
7.8 Hz, 1H), 2.84 (td, J = 11.4, 5.4 Hz, 1H), 2.50-2.42(m, 1H),
2.36-2.33(m, 1H), 2.01-1.96 (m, 2H), 1.58 (d, J = 6.0 Hz, 3H),
1.57 (s, 9H), 1.48 (s, 9H). 13C NMR (150 MHz, Chloroform-d):
δ 153.8, 152.3, 142.8, 138.9, 135.2, 129.3, 128.7, 127.9, 127.3,
125.3, 122.9, 122.7, 116.5, 81.0, 79.7, 56.3, 45.7, 41.3, 36.0,
28.3, 28.2, 17.9. HRMS (ESI) exact mass calculated for [M+H+]
(C24H35N2O4): m/z 415.2591; found: 415.2601.
According to method A, flash column chromatography (SiO2: 5%
ethyl acetate in petroleum ether) provided this compound in 60%
yield (91.1 mg, 0.180 mmol) as foam solid. mp: 83-84 oC.
IR (KBr) νꢀ=ꢀ2972, 2927, 1706, 1480, 1391, 1160, 894, 750. 1H
NMR (600 MHz, Chloroform-d): δ 7.48 (bs, 1H), 7.14(t, J =
7.8 Hz, 1H), 7.07 (t, J = 7.8 Hz, 1H), 6.95 (d, J = 7.2 Hz, 1H),
6.83 (t, J = 7.8 Hz, 1H),6.79 (s, 1H), 6.74 (t, J = 7.2 Hz, 2H ),
5.98 (s, 1H), 5.07 (s, 1H), 5.03 (s, 1H), 3.80 (s, 3H), 3.67-3.63
(m, 1H), 3.25 (d, J = 13.8 Hz, 1H), 2.85-2.80 (m, 1H), 2.69 (tt, J
= 11.5, 6.0 Hz, 1H), 1.87-1.80 (m, 2H), 1.56 (s, 9H), 1.45 (s, 9H).
13C NMR (150 MHz, Chloroform-d): δ 156.0, 153.8, 152.2,
145.1, 142.8, 131.2, 129.9, 128.5, 127.8, 123.3, 122.4, 120.5,
119.4, 110.2, 80.9, 79.7, 56.4, 55.1, 45.5, 43.9, 28.4, 28.3.
HRMS (ESI) exact mass calculated for [M+H+] (C30H39N2O5):
m/z 507.2853; found: 507.2849.
4.2.10
Di-tert-butyl
(3aS)-3a-allyl-5-methoxy-2,3,3a,8a-
tetrahydro pyrrolo [2,3-b] indole-1,8- dicarboxylate (4a)
According to method A, except that Ni (COD)2 10%, L5 15%,
2,6-diamine-Pyridine 30% was used, flash column
chromatography (SiO2: 2% ethyl acetate in petroleum ether)
provided this compound in 54% yield (69.7 mg, 0.162 mmol) as
foam solid.
4.2.7
Di-tert-butyl
(3aS)-3a-allyl-2,3,3a,8a-
tetrahydropyrrolo[2,3-b] indole-1,8 -dicarboxylate (3g)
According to method A, except that Ni (COD)2 10%, L5 15%,
2,6-diamine-Pyridine 30% was used, flash column
chromatography (SiO2: 2% ethyl acetate in petroleum ether)
provided this compound in 56% yield (67.3 mg, 0.168 mmol) as
foam solid. mp: 89-91 oC.
IR (KBr) νꢀ=ꢀ2971, 2927, 1704, 1485, 1394, 1256, 1158, 890,
761. 1H NMR (600 MHz, Chloroform-d): δ 7.43 (bs, 1H), 6.73
(dd, J = 9.0, 3.0 Hz, 1H), 6.66 (d, J = 3.0 Hz, 1H), 5.98 (s, 1H),
5.56 (td, J = 16.8, 7.8 Hz, 1H), 5.05 (d, J = 16.8 Hz, 1H), 4.99 (d,
J = 10.8 Hz, 1H), 3.78 (s, 3H), 3.71 (dd, J = 10.8, 7.8 Hz, 1H),
2.85 (td, J = 11.4, 5.4 Hz, 1H), 2.50-2.47 (m 1H), 2.40 (dd, J =
13.8, 7.8 Hz, 1H), 2.03-1.93 (m, 2H), 1.54 (s, 9H), 1.47 (s, 9H).
13C NMR (150 MHz, Chloroform-d): δ 156.1, 153.9, 152.5,
136.6, 133.0, 118.7, 112.6, 109.1, 80.9, 80.1, 55.6, 45.6, 42.5,
28.4, 28.3. HRMS (ESI) exact mass calculated for [M+H+]
(C24H35N2O5): m/z 431.2540; found: 431.2576.
IR (KBr) νꢀ=ꢀ2974, 2928, 1707, 1477, 1398, 1159, 1091, 887,
753. 1H NMR (600 MHz, Chloroform-d): δ 7.56 (bs, 1H), 7.20
(t, J = 12.0 Hz, 1H), 7.10 (d, J = 6.0 Hz, 1H), 7.02 (t, J = 12.0
Hz, 1H), 6.02 (s, 1H), 5.62-5.53 (m, 1H), 5.06-4.99 (m, 2H),
3.75-3.71 (m, 1H), 2.84 (td, J = 12.0, 6.0 Hz, 1H), 2.52-2.48 (m,
1H), 2.44-2.40 (m, 1H), 2.08-2.04 (m, 1H), 2.01-1.95 (m, 1H),
1.55 (s, 9H), 1.47 (s, 9H). 13C NMR (150 MHz, Chloroform-d):
δ 154.0, 152.4, 143.0, 133.1, 128.1, 123.1, 122.9, 118.7, 81.2,
79.9, 56.2, 45.8, 42.6, 28.4, 28.3. HRMS (ESI) exact mass
calculated for [M+H+] (C23H33N2O4): m/z 401.2435; found:
401.2433.
4.2.11
Di-tert-butyl(3aS)-5-methoxy-3a-(2-phenylallyl)-
2,3,3a,8a-tetrahydropyrrolo[2,3-b] indole-1,8-dicarboxylate
(4b)
According to method A, flash column chromatography (SiO2: 5%
ethyl acetate in petroleum ether) provided this compound in 58%
yield (88.2 mg, 0.174 mmol) as foam solid. mp: 117-119 oC.
4.2.8
Di-tert-butyl(3aS)-3a-(2-methylallyl)-2,3,3a,8a-
tetrahydropyrrolo [2,3-b] indole -1,8-dicarboxylate (3h)
IR (KBr) νꢀ=ꢀ2971, 2929, 1704, 1476, 1390, 1158, 889, 750. 1H
NMR (600 MHz, Chloroform-d): δ 7.36 (bs, 1H), 7.22-7.15 (m,
5H), 6.62 (dd, J = 8.8, 2.6 Hz, 1H), 6.43 (d, J = 1.2 Hz, 1H), 6.06
(s, 1H), 5.21 (s, 1H), 5.04 (s, 1H), 3.65 (s, 3H), 3.62-3.59 (m,
1H), 3.02 (d, J = 13.7 Hz, 1H), 2.84 (d, J = 13.7 Hz, 1H), 2.76-
According to method A, flash column chromatography (SiO2: 2%
ethyl acetate in petroleum ether) provided this compound in 42%
yield (52.2 mg, 0.126 mmol) as foamy semisolid.
IR (KBr) νꢀ=ꢀ2974, 2927, 1707, 1476, 1395, 1162, 892, 753. 1H
NMR (600 MHz, Chloroform-d): δ 7.52 (bs, 1H), 7.18 (t, J =
7.7 Hz, 1H), 7.10 (d, J = 7.2 Hz, 1H), 7.00 (t, J = 7.4 Hz,, 1H),
6.09 (s, 1H), 4.75 (s, 1H), 4.64 (s, 1H), 3.71 (dd, J = 10.8, 7.8 Hz,
1H), 2.82 (tt, J = 11.5, 5.2 Hz, 1H), 2.49 (d, J = 13.4 Hz, 1H),
2.41 (d, J = 13.4 Hz, 1H), 2.10-1.99 (m, 2H), 1.54 (s, 9H), 1.47
(s, 9H), 1.43 (s, 3H). 13C NMR (150 MHz, Chloroform-d): δ
154.0, 152.3, 142.9, 141.4, 135.2, 128.1, 123.1, 115.2, 81.0, 79.7,
56.4, 53.4, 46.1, 45.6, 28.4, 28.3, 23.9. HRMS (ESI) exact mass
calculated for [M+H+] (C24H35N2O4): m/z 415.2591; found:
415.2572.
2.71 (m, 1H), 1.83-1.81 (m, 2H), 1.57 (s, 9H), 1.46 (s, 9H). 13
C
NMR (150 MHz, Chloroform-d): δ 155.6, 153.7, 152.3, 144.9,
142.0, 136.3, 128.0, 127.1, 126.2, 117.6, 112.9, 109.5, 80.7, 80.2,
56.8, 55.4, 45.7, 43.1, 28.3, 28.2. HRMS (ESI) exact mass
calculated for [M+H+] (C30H39N2O5): m/z 507.2583; found:
507.2845.
4.2.12 Di-tert-butyl3a-(2-(4-fluorophenyl) allyl)-5-methoxy-
2,3,3a, 8a-tetrahydropyrrolo [2,3-b] indole-1,8-dicarboxylate
(4c)
According to method A, flash column chromatography (SiO2: 5%
ethyl acetate in petroleum ether) provided this compound in 56%
yield (88.1 mg, 0.168 mmol) as foam solid.
4.2.9
Di-tert-butyl(E)-3a-(but-2-en-1-yl)-2,3,3a,8a-tetrahy
dropyrrolo [2,3-b] indole-1,8- dicarboxylate (3i)
This compound can be prepared from the coupling of but-3-en-
2-yl methyl carbonate with di-tert-butyl 3a-chloro-2,3,3a,8a-
tetrahydropyrrolo[2,3-b] indole -1,8-dicarboxylate, using
IR (KBr) νꢀ=ꢀ2963, 2929, 1700, 1498, 1395, 1259, 828. 1H NMR
(600 MHz, Chloroform-d): δ 7.40 (bs, 1H), 7.07 (s, 2H), 6.87 (t,
J = 7.8 Hz, 2H), 6.61 (d, J = 8.4 Hz, 1H), 6.41 (s, 1H), 6.03 (s,

6
Tetrahedron
1H), 5.14 (s, 1H), 5.05 (s, 1H), 3.67 (s, 3H), 3.64-3.62 (m, 1H),
According to method A, flash column chromatography (SiO2: 3%
ACCEPTED MANUSCRIPT
3.00 (d, J = 13.2 Hz, 1H), 2.83 (d, J = 13.2 Hz, 1H), 2.77-2.73
(m, 1H), 1.88-1.87 (m, 2H), 1.56 (s, 9H), 1.46 (s, 9H). 13C NMR
(150 MHz, Chloroform-d): δ 162.7, 161.1, 155.7, 152.3, 144.1,
138.0, 127.9, 117.6, 114.8, 114.7, 112.7, 109.8, 80.8, 80.0, 56.9,
55.5, 45.7, 43.5, 28.4, 28.3. 19F NMR (564 MHz, Chloroform-
d): δ 115.5. HRMS (ESI) exact mass calculated for [M+H+]
(C30H38FN2O5): m/z 525.2759; found: 525.2770.
ethyl acetate in petroleum ether) provided this compound in 51%
yield (60.0 mg, 0.153 mmol) as colorless oil.
IR (KBr) νꢀ=ꢀ2922, 2853, 1716, 1449, 1380, 1257, 761. 1H NMR
(600 MHz, Chloroform-d): δ 7.60 (bs, 1H), 7.24-7.21 (m, 3H),
7.19-7.14 (m, 3H), 7.01 (d, J = 6.0 Hz, 1H), 6.93 (t, J = 12.0 Hz,
1H), 5.92 (s, 1H), 5.20 (s, 1H), 4.92 (s, 1H), 3.76 (s, 3H), 3.67-
3.66 (m, 1H), 3.65 (s, 3H), 2.99 (d, J = 12.0 Hz, 1H), 2.88 (d, J =
12.0 Hz, 1H), 2.82-2.77 (m, 1H), 1.96-1.95 (m, 2H). 13C NMR
(150 MHz, Chloroform-d): δ 153.8, 144.6, 144.5, 142.1, 141.5,
134.0, 128.4, 128.3, 127.5, 127.4, 126.3, 126.2, 123.3, 118.1,
116.3, 57.0, 52.6, 52.5, 45.8, 43.2, 43.1. HRMS (ESI) exact mass
calculated for [M+H+] (C23H25N2O4): m/z 393.1809; found:
393.1823.
4.2.13
Di-tert-butyl
(3aS)-5-chloro-3a-(2-phenylallyl)-
2,3,3a,8a-tetrahydro pyrrolo[2,3-b] indole-1,8-dicarboxylate
(5)
According to method A, flash column chromatography (SiO2: 2%
ethyl acetate in petroleum ether) provided this compound in 65%
yield (99.7 mg, 0.195 mmol) as foam solid. mp: 59-60 oC.
4.2.17 8-(Tert-butyl) 1-methyl (3aS)-3a-(2-phenylallyl)-
2,3,3a,8a-tetrahydropyrrolo [2,3-b] indole-1,8-dicarboxylate
(9)
IR (KBr) νꢀ=ꢀ2973, 2927, 1707, 1475, 1385, 1159, 893, 773. 1H
NMR (600 MHz, Chloroform-d): δ 7.40 (bs, 1H), 7.22-7.17 (m,
3H), 7.12 (d, J = 6.6 Hz, 2H), 7.00 (dd, J = 8.4, 1.8 Hz, 1H), 6.83
(d, J = 1.8 Hz, 1H), 6.07 (s, 1H), 5.21 (s, 1H), 5.04 (s, 1H), 3.66-
3.63 (m, 1H), 3.04 (d, J = 13.8 Hz, 1H), 2.84 (d, J = 13.8 Hz,
1H), 2.75-2.70 (m, 1H), 1.86-1.83 (m, 2H), 1.56 (s, 9H), 1.45 (s,
9H). 13C NMR (150 MHz, Chloroform-d): δ153.6, 152.0, 144.8,
141.5, 141.4, 135.9, 128.1, 127.9, 127.5, 127.3, 126.2, 123.8,
117.8, 81.4, 80.1, 56.7, 45.8, 43.3, 38.3, 28.3, 28.2. HRMS
(ESI) exact mass calculated for [M+H+] (C29H36ClN2O4): m/z
511.2358; found: 511.2341.
According to method A, flash column chromatography (SiO2: 3%
ethyl acetate in petroleum ether) provided this compound in 66%
yield (86.0 mg, 0.198 mmol) as foam solid. mp: 81-82 oC.
IR (KBr) νꢀ=ꢀ2961, 2924, 1693, 1454, 1398, 1154, 906, 746. 1H
NMR (600 MHz, Chloroform-d): δ 7.54 (bs, 1H), 7.24-7.19 (m,
5H), 7.12 (t, J = 12.0 Hz, 1H), 6.96 (d, J = 6.0Hz, 1H), 6.87 (t, J
= 6.0 Hz, 1H), 5.99 (s, 1H), 5.24 (s, 1H), 5.00 (s, 1H), 3.68 (s,
3H), 3.66 (m, 1H), 3.00 (d, J = 13.8 Hz, 1H), 2.85 (d, J = 13.8
Hz, 1H), 2.80-2.75 (m, 1H), 1.91-1.88 (m, 2H), 1.56 (s, 9H). 13C
NMR (150 MHz, Chloroform-d): δ 155.1, 152.3, 144.8, 142.4,
141.8, 134.2, 128.2, 127.3, 126.2, 123.2, 122.9, 117.8, 116.5,
81.1, 57.0, 52.4, 45.9, 42.9, 28.3. HRMS (ESI) exact mass
calculated for [M+Na+] (C26H30N2NaO4): m/z 457.2098; found:
457.2075.
4.2.14
Di-benzyl
(3aS)-3a-(2-phenylallyl)-2,3,3a,8a-
tetrahydropyr rolo [2,3-b] indole -1,8- dicarboxylate (6)
According to method A, flash column chromatography (SiO2: 3%
ethyl acetate in petroleum ether) provided this compound in 42%
yield (68.6 mg, 0.126 mmol) as foam solid.
IR (KBr) νꢀ=ꢀ1707, 1410, 1265, 1095, 904, 748, 698. 1H NMR
(600 MHz, Chloroform-d): δ 7.63 (bs, 1H), 7.36-7.30 (m, 10H),
7.15 (d, J = 4.8 Hz, 4H), 7.11 (m, 2H), 7.01 (d, J = 7.8 Hz, 1H),
6.93 (t, J = 7.2 Hz, 1H), 6.09 (s, 1H), 5.11 (s, 2H), 5.03 (d, J =
12.0 Hz, 2H), 4.91 (s, 2H), 3.75-3.72 (m, 1H), 3.01 (d, J = 8.4
Hz, 1H), 2.87-2.82 (m, 2H), 1.98-1.91 (m, 2H). 13C NMR (150
MHz, Chloroform-d): δ 154.4, 153.1, 144.6, 142.0, 141.4,
137.8, 136.5, 136.2, 134.0, 128.3, 128.1, 128.0, 127.9, 127.3,
126.1, 123.3, 117.9, 116.5, 67.2, 66.9, 45.9, 43.0, 35.7. HRMS
(ESI) exact mass calculated for [M+H+] (C35H33N2O4): m/z
545.2435; found: 545.2435.
4.2.18 8-Benzyl-1-methyl (3aS)-3a-(2-phenylallyl)-2,3,3a,8a-
tetrahydro pyrrolo[2,3-b] indole-1,8-dicarboxylate (10)
According to method A, flash column chromatography (SiO2: 3%
ethyl acetate in petroleum ether) provided this compound in 62%
yield (87.2 mg, 0.186 mmol) as colorless oil.
IR (KBr) νꢀ=ꢀ2948, 1706, 1398, 1265, 1030, 902, 751, 700. 1H
NMR (600 MHz, Chloroform-d): δ 7.60 (bs, 1H), 7.43-7.41 (m,
2H), 7.37 (t, J = 7.2 Hz, 2H), 7.32 (t, J = 7.2 Hz, 1H), 7.17-7.11
(m, 6H), 7.00 (d, J = 7.2 Hz, 1H), 6.90 (t, J = 7.2 Hz, 1H), 6.01
(s, 1H), 5.22 (s, 2H), 5.13 (s, 1H), 4.91 (s, 1H), 3.68 (s, 1H), 3.45
(s, 3H), 3.01 (d, J = 13.8 Hz, 1H), 2.86 (d, J = 13.8 Hz, 1H),
2.82-2.76 (m, 1H), 1.96-1.92 (m, 2H). 13C NMR (150 MHz,
Chloroform-d): δ 155.0, 153.1, 152.9, 144.6, 142.0, 141.4,
136.2, 134.0, 128.4, 128.3, 128.2, 128.1, 128.0, 127.4, 127.3,
126.2, 126.1, 123.3, 117.9, 116.4, 67.4, 57.1, 52.2, 45.8, 43.2,
43.1. HRMS (ESI) exact mass calculated for [M+H+]
(C29H29N2O4): m/z 469.2122; found: 469.2131.
4.2.15
Methyl
(3aS)-3a-(2-phenylallyl)-8-tosyl-3,3a,8,8a-
tetrahydro pyrrolo [2,3-b] indole-1(2H)-carboxylate (7)
According to method A, flash column chromatography (SiO2:
10% ethyl acetate in petroleum ether) provided this compound in
63% yield (92.3 mg, 0.189 mmol) as foam solid. mp: 51-53 oC.
IR (KBr) νꢀ=ꢀ2925, 1708, 1598, 1449, 1374, 1168, 1000, 762,
662, 574. 1H NMR (600 MHz, Chloroform-d): δ 7.70 (bs, 2H),
7.49 (s, 1H), 7.23 (d, J = 6.0 Hz, 5H), 7.18 (t, J = 6.0 Hz, 1H),
7.14 (s, 2H), 6.91 (d, J = 24.0 Hz, 2H), 5.91 (s, 1H), 5.19 (t, J =
6.0 Hz, 1H), 4.67 (s, 1H), 3.66-3.61 (m, 4H), 2.72 (td, J = 12.0,
6.0 Hz, 1H), 2.67 (d, J = 12.0 Hz, 1H), 2.35 (s, 3H), 2.29 (d, J =
18.0 Hz, 1H), 1.85-1.79 (m, 1H), 1.68 (dd, J = 18.0, 6.0 Hz, 1H).
13C NMR (150 MHz, Chloroform-d): δ 154.6, 143.9, 143.8,
141.5, 137.0, 135.1, 129.5, 128.5, 128.2, 127.4, 126.9, 126.2,
124.3, 118.1, 116.8, 83.2, 57.9, 52.4, 45.7, 42.2, 36.7, 35.3, 21.4.
HRMS (ESI) exact mass calculated for [M+Na+]
(C28H28N2NaO4S): m/z 511.1662; found: 511.2437.
4.2.19
Di-tert-butyl
(3aS)-8a-methyl-3a-(2-phenylallyl)-
2,3,3a,8a-tetrahydropyrrolo [2,3-b] indole-1,8-dicarboxylate
(11)
According to method A, flash column chromatography (SiO2: 5%
ethyl acetate in petroleum ether) provided this compound in 45%
yield (66.3 mg, 0.135 mmol) as foam solid. mp: 94-96 oC.
IR (KBr) νꢀ=ꢀ2979, 2929, 1705, 1475, 1375, 1150, 1056, 849,
748. 1H NMR (600 MHz, Chloroform-d): δ 7.65 (bs, 1H), 7.33-
7.28 (m, 4H), 7.26-7.24 (m, 1H), 7.12 (t, J = 7.8 Hz, 1H), 6.89 (d,
J = 6.6 Hz, 1H), 6.84 (t, J = 7.8 Hz, 1H), 5.24 (s, 1H), 4.68 (s,
1H), 3.25 (s, 1H), 2.93 (d, J = 12.0 Hz, 1H), 2.65 (d, J = 6.0 Hz,
1H), 2.45 (d, J = 12.0 Hz, 1H), 1.98 (s, 3H), 1.70-1.64 (m, 2H),
4.2.16
Di-methyl
(3aS)-3a-(2-phenylallyl)-2,3,3a,8a-
tetrahydropyr rolo[2,3-b] indole-1,8- dicarboxylate (8)

1.60 (s, 9H), 1.40 (s, 9H). 13C NMR (150 MHz, Chloroform-d):
IR (KBr) νꢀ=ꢀ2960, 1708, 1607, 1264, 1171, 1111, 1027, 849,
771. 1H NMR (600 MHz, Chloroform-d): δ 7.98 (d, J = 9.0 Hz,
2H), 6.91 (d, J = 9.0 Hz, 2H), 6.33 (dt, J = 16.8, 10.2 Hz, 1H),
6.06 (dd, J = 15.0, 10.8 Hz, 1H), 5.76-5.71 (m, 1H), 5.10 (d, J =
16.8 Hz, 1H), 4.98 (d, J = 10.2 Hz, 1H), 4.35 (t, J = 7.2 Hz, 2H),
3.85 (s, 3H), 2.06 (d, J = 7.2 Hz, 2H), 1.69 (t, J = 7.2 Hz, 2H),
0.97 (s, 6H). 13C NMR (150 MHz, Chloroform-d): δ 166.4,
163.2, 137.1, 133.6, 131.5, 131.3, 122.8, 115.2, 113.5, 61.9, 55.4,
45.6, 39.7, 33.1, 27.2. HRMS (ESI) exact mass calculated for
[M+H+] (C18H25O3): m/z 287.1798; found: 287.1807.
ACCEPTED MANUSCRIPT
δ 152.5, 144.1, 142.3, 133.3, 128.3, 127.7, 127.4, 126.4, 124.3,
122.0, 118.4, 89.5, 81.0, 58.7, 45.9, 39.3, 28.5, 20.6. HRMS
(ESI) exact mass calculated for [M+H+] (C30H39N2O4): m/z
491.2904; found: 491.2916.
4.2.20
Tert-butyl
(3aS)-3a-(2-phenylallyl)-2,3,3a,8a-
tetrahydro-8H-furo [2,3-b] indole -8 -carboxylate (12)
According to method A, flash column chromatography (SiO2: 3%
ethyl acetate in petroleum ether) provided this compound in 47%
yield (53.2 mg, 0.141 mmol) as foam solid.
4.2.24 (E)-3,3-Dimethylocta-5,7-dien-1-yl 4-acetylbenzoate
(16)
IR (KBr) νꢀ=ꢀ2975, 2930, 2870, 1706, 1480, 1388, 1161, 1029,
906, 755, 703. 1H NMR (600 MHz, Chloroform-d): δ 7.74 (bs,
1H), 7.25-7.17 (m, 6H), 7.06 (d, J = 7.2 Hz, 1H), 6.92 (s, 1H),
5.52 (s, 1H), 5.11 (s, 1H), 4.88 (s, 1H), 3.87 (t, J = 7.8 Hz, 1H),
3.36-3.32 (m, 1H), 3.09 (d, J = 13.2 Hz, 1H), 2.97 (d, J = 13.8
Hz, 1H), 2.17-2.03 (m, 2H), 1.45 (s, 9H). 13C NMR (100 MHz,
Chloroform-d): δ 151.9, 145.1, 142.9, 141.9, 133.3, 128.2,
127.4, 126.4, 123.5, 122.4, 117.7, 114.2, 96.0, 80.8, 67.1, 56.2,
43.4, 39.8, 28.3. HRMS (ESI) exact mass calculated for [M+H+]
(C24H28NO3): m/z 378.2064; found: 378.2074.
According to method B, flash column chromatography (SiO2: 5%
ethyl acetate in petroleum ether) provided this compound in 50%
yield (45.1 mg, 0.150 mmol) as colorless oil
IR (KBr) νꢀ=ꢀ2961, 2925, 1722, 1692, 1271, 1113, 1010, 958,
769, 697. 1H NMR (600 MHz, Chloroform-d): δ 8.10 (d, J = 8.4
Hz, 2H), 7.99 (d, J = 8.4 Hz, 2H), 6.33 (dt, J = 16.8, 10.2 Hz,
1H), 6.06 (dd, J = 15.0, 10.8 Hz, 1H), 5.75-5.70 (m, 1H), 5.10 (d,
J = 16.8 Hz, 1H), 4.98 (d, J = 10.2 Hz, 1H), 4.40 (t, J = 7.8 Hz,
2H), 2.63 (s, 3H), 2.06 (d, J = 7.8 Hz, 2H), 1.72 (t, J = 7.8 Hz,
2H), 0.98 (s, 6H). 13C NMR (150 MHz, Chloroform-d): δ 197.5,
165.8, 140.1, 137.0, 134.2, 133.7, 131.1, 129.7, 128.2, 115.3,
62.7, 45.6, 39.6, 33.1, 27.2, 26.8. HRMS (ESI) exact mass
calculated for [M+H+] (C19H25O3): m/z 301.1798; found:
301.1800.
4.2.21
1,
8-Di-tert-butyl
2-methyl
(3aS)-3a-(2-(2-
methoxyphenyl) allyl)-2,3,3a,8a- tetrahydropyrrolo[2,3-b]
indole-1,2,8-tricarboxylate (13)
According to method A, flash column chromatography (SiO2: 5%
ethyl acetate in petroleum ether) provided this compound in 56%
yield (94.5 mg, 0.168 mmol) as foam solid. mp: 66-68 oC.
4.2.25 (E)-4-(3,3-Dimethylocta-5,7-dien-1-yl) phenol (17)
IR (KBr) νꢀ=ꢀ2968, 2926, 2859, 1715, 1483, 1400, 1159, 1021,
903, 750. 1H NMR (600 MHz, Chloroform-d): δ 7.48 (bs, 1H),
7.16 (t, J = 12.0 Hz, 1H), 7.10 (t, J = 6.0 Hz, 1H), 6.90 (dd, J =
18.0, 6.0 Hz, 2H), 6.82 (t, J = 6.0 Hz, 1H), 6.78 (t, J = 6.0 Hz,
1H), 6.74 (d, J = 6.0 Hz, 1H), 6.02 (s, 1H), 5.09 (s, 1H), 5.07 (s,
1H), 3.79-3.75 (m, 1H), 3.76 (s, 3H), 3.67 (s, 3H), 3.14 (t, J = 6.0
Hz, 1H), 2.73 (d, J = 18.0Hz, 1H), 2.28 (q, J = 6.0 Hz, 1H), 2.01
(t, J = 12.0 Hz, 1H), 1.59 (s, 9H), 1.37 (s, 9H). 13C NMR (150
MHz, Chloroform-d): δ 173.0, 156.0, 152.3, 144.1, 141.9,
134.8, 131.3, 129.9, 128.5, 128.2, 123.0, 120.6, 120.0, 110.4,
81.2, 80.5, 65.3, 59.4, 55.2, 51.9, 42.9, 41.9, 28.3, 28.2. HRMS
(ESI) exact mass calculated for [M+H+] (C32H41N2O7): m/z
565.2908; found: 565.2929.
According to method B, flash column chromatography (SiO2: 5%
ethyl acetate in petroleum ether) provided this compound in 52%
yield (35.9 mg, 0.156 mmol) as colorless oil.
IR (KBr) νꢀ=ꢀ3363, 2953, 2862, 1605, 1511, 1453, 1231, 1005,
835. 1H NMR (600 MHz, Chloroform-d): δ 7.05 (d, J = 7.8 Hz,
2H), 6.76 (d, J = 8.4 Hz, 2H), 6.35 (dt, J = 16.8, 10.2 Hz, 1H),
6.08 (dd, J = 15.0, 10.2 Hz, 1H), 5.78-5.73 (m, 1H), 5.12 (d, J =
16.8 Hz, 1H), 4.99 (d, J = 10.2 Hz, 1H), 2.52-2.49 (m, 2H), 2.06
(d, J = 7.8 Hz, 2H), 1.49-1.46 (m, 2H), 0.95 (s, 6H). 13C NMR
(150 MHz, Chloroform-d): δ 153.3, 137.2, 135.5, 133.2, 132.0,
129.3, 115.1, 114.9, 45.1, 44.4, 33.8, 29.7, 27.0. HRMS (ESI)
exact mass calculated for [M+H+] (C16H23O): m/z 231.1743;
found: 231.1746.
4.2.22 (E)-3,3-Dimethylocta-5,7-dien-1-yl benzoate (14)
4.2.26 (E)-6,6-Dimethyltrideca-1,3-diene (18)
According to method B, flash column chromatography (SiO2: 1%
ethyl acetate in petroleum ether) provided this compound in 78%
yield (60.5 mg, 0.234 mmol) as colorless oil.
According to method B, flash column chromatography (SiO2:
0.5% ethyl acetate in petroleum ether) provided this compound in
41% yield (25.6 mg, 0.123 mmol) as colorless oil.
IR (KBr) νꢀ=ꢀ2959, 2925, 2862, 1715, 1226, 1114, 947, 714. 1H
NMR (600 MHz, Chloroform-d): δ 8.03 (d, J = 7.2 Hz, 2H),
7.55 (t, J = 7.2 Hz, 1H), 7.43 (t, J = 7.2 Hz, 2H), 6.33 (dt, J =
17.4, 10.2 Hz, 1H), 6.07 (dd, J = 15.0, 10.2 Hz, 1H), 5.77-5.71
(m, 1H), 5.11 (d, J = 10.8 Hz, 1H), 4.98 (d, J = 10.2 Hz, 1H),
4.38 (t, J = 7.8 Hz, 2H), 2.07 (d, J = 7.8 Hz, 2H), 1.71 (t, J = 7.8
Hz, 2H), 0.98 (s, 6H). 13C NMR (150 MHz, Chloroform-d): δ
166.6, 137.1, 133.7, 132.8, 131.2, 130.4, 129.5, 128.3, 115.2,
62.2, 45.6, 39.7, 33.1, 27.2. HRMS (ESI) exact mass calculated
for [M+H+] (C17H23O2): m/z 259.1693; found: 259.1693.
IR (KBr) νꢀ=ꢀ2926, 2859, 1703, 1462, 1374, 977, 724. 1H NMR
(600 MHz, Chloroform-d): δ 6.33 (dt, J = 16.8, 10.2 Hz, 1H),
6.03 (dd, J = 15.6, 10.2 Hz, 1H), 5.74-5.69 (m, 1H), 5.09 (d, J =
16.8 Hz, 1H), 4.96 (d, J = 10.2 Hz, 1H), 1.96 (d, J = 7.2 Hz, 2H),
1.32-1.22 (m, 12H), 0.89 (t, J = 7.2 Hz, 3H), 0.84 (s, 6H). 13
C
NMR (150 MHz, Chloroform-d): δ 137.4, 133.0, 132.5, 114.6,
45.2, 42.0, 33.7, 31.9, 30.5, 27.1, 24.0, 22.7, 14.1. HRMS (ESI)
exact mass calculated for [M+H+] (C15H29): m/z 209.2264; found:
209.2266.
4.2.23 (E)-3,3-Dimethylocta-5,7-dien-1-yl 4-methoxybenzoate
(15)
4.2.27 (E)-3,3-Dimethylocta-5,7-dien-1-yl 4-methylbenzene
sulfonate (19)
According to method B, flash column chromatography (SiO2: 2%
ethyl acetate in petroleum ether) provided this compound in 53%
yield (45.9 mg, 0.159 mmol) as colorless oil.
According to method B, flash column chromatography (SiO2: 5%
ethyl acetate in petroleum ether) provided this compound in 70%
yield (64.8 mg, 0.210 mmol) as colorless oil.

8
Tetrahedron
IR (KBr) νꢀ=ꢀ3384, 2958, 2928, 1719, 1600, 1453, 1173, 1125,
55.9, 45.8, 41.2, 28.4, 28.3. HRMS (ESI) exact mass calculated
ACCEPTED MANUSCRIPT
1037, 1003, 816, 680, 562. 1H NMR (600 MHz, Chloroform-d):
δ 7.78 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 7.8 Hz, 2H), 6.27 (dt, J =
17.4, 10.2 Hz, 1H), 5.97 (dd, J = 15.6, 10.2 Hz, 1H), 5.62-5.57
(m, 1H), 5.08 (d, J = 16.8 Hz, 1H), 4.98 (d, J = 10.2 Hz, 1H),
4.08 (t, J = 7.8 Hz, 2H), 2.45 (s, 3H), 1.92 (d, J = 7.8 Hz, 2H),
1.57 (t, J = 7.8 Hz, 2H), 0.85 (s, 6H). 13C NMR (150 MHz,
Chloroform-d): δ 144.7, 136.9, 133.8, 133.1, 130.6, 129.8,
127.8, 115.4, 67.9, 45.3, 39.6, 33.0, 27.0, 21.6. HRMS (ESI)
exact mass calculated for [M+H+] (C17H25O3S): m/z 309.1519;
found: 309.1529.
for [M+H+] (C25H34ClN2O4): m/z 461.2202; found: 461.2213.
4.2.31 8-(Tert-butyl) 1-methyl (3aS)-3a-((E)-penta-2,4-dien-1-
yl)-2,3,3a,8a-tetrahydro
dicarboxylate (23)
pyrrolo[2,3-b]
indole-1,8-
According to method B, flash column chromatography (SiO2: 5%
ethyl acetate in petroleum ether) provided this compound in 49%
yield (56.5 mg, 0.147 mmol) as foam solid. mp: 55-56oC.
IR (KBr) νꢀ=ꢀ2924, 2858, 1707, 1450, 1394, 1156, 1011, 752. 1H
NMR (600 MHz, Chloroform-d): δ 7.61 (bs, 1H), 7.22 (t, J =
7.2 Hz, 1H), 7.10 (d, J = 1.2 Hz, 1H), 7.04 (t, J = 7.2 Hz, 1H),
6.20 (dt, J = 16.8, 10.2 Hz, 1H), 6.06 (dd, J = 15.0, 10.8 Hz, 1H),
5.96 (s, 1H), 5.47-5.42 (m, 1H), 5.10 (d, J = 17.4 Hz, 1H), 4.98
(d, J = 10.2 Hz, 1H)，3.75 (dd, J = 10.2, 8.4 Hz, 1H), 3.71 (s,
3H), 2.90 (td, J = 12.0, 5.4 Hz, 1H), 2.52 (dd, J = 13.8, 7.2 Hz,
1H), 2.44 (dd, J = 14.4, 8.4 Hz, 1H), 2.12 (dd, J = 6.6, 5.4 Hz,
1H), 2.04-1.99 (m, 1H), 1.55 (s, 9H). 13C NMR (150 MHz,
Chloroform-d): δ 155.1, 152.3, 142.7, 136.5, 134.9, 134.5,
128.5, 128.4, 123.4, 122.7, 116.8, 116.5, 81.3, 79.8, 56.6, 52.4,
45.8, 41.2, 28.3. HRMS (ESI) exact mass calculated for [M+H+]
(C22H29N2O4): m/z 385.2122; found: 385.2142.
4.2.28 (E)-3,3-Dimethylocta-5,7-dien-1-yl 6-bromohexanoate
(20)
According to method B, flash column chromatography (SiO2: 5%
ethyl acetate in petroleum ether) provided this compound in 47%
yield (46.7 mg, 0.141 mmol) as colorless oil.
IR (KBr) νꢀ=ꢀ2951, 2866, 1730, 1460, 1362, 1258, 1178, 978,
732, 650. 1H NMR (600 MHz, Chloroform-d): δ 6.32 (dt, J =
17.4, 10.2 Hz, 1H), 6.04 (dd, J = 15.0, 10.2 Hz, 1H), 5.72-5.67
(m, 1H), 5.10 (d, J = 16.8 Hz, 1H), 4.98 (d, J = 10.2 Hz, 1H),
4.12 (t, J = 7.8 Hz, 2H), 3.53 (t, J = 6.6 Hz, 2H), 2.30 (t, J = 7.8
Hz, 2H), 2.00 (d, J = 7.8 Hz, 2H), 1.78 (t, J = 7.8 Hz, 2H), 1.64
(t, J = 7.8 Hz, 2H), 1.55 (t, J = 7.8 Hz, 2H), 1.48-1.45 (m, 2H),
0.91 (s, 6H). 13C NMR (150 MHz, Chloroform-d): δ 173.5,
137.1, 133.6, 131.2, 115.2, 61.6, 45.5, 44.7, 39.6, 34.2, 33.0,
32.2, 27.1, 26.4, 24.2. HRMS (ESI) exact mass calculated for
[M+H+] (C16H28BrO2): m/z 331.1267; found: 331.2363.
4.2.32 1,8-di-tert-butyl 2-methyl (2S,3aS,8aR)-3a-((E)-penta-
2,4-dien-1-yl)-2,3,3a,8a- tetrahydropyrrolo[2,3-b] indole-
1,2,8-tricarboxylate (24)
According to method B, flash column chromatography (SiO2:
10% ethyl acetate in petroleum ether) provided this compound in
58% yield (84.3 mg, 0.174 mmol) as foam solid. mp: 73-75 oC.
4.2.29
Di-tert-butyl
(3aS)-3a-((E)-penta-2,4-dien-1-yl)-
2,3,3a,8a-tetrahydropyrrolo[2,3-b] indole-1,8-dicarboxylate
(21)
IR (KBr) νꢀ=ꢀ2973, 2925, 2856, 1749, 1711, 1335, 1158, 1011,
900, 749. 1H NMR (600 MHz, Chloroform-d): δ 7.62 (bs, 1H),
7.24 (t, J = 7.8 Hz, 1H), 7.10 (d, J = 6.6 Hz, 1H), 7.05 (t, J = 7.8
Hz, 1H), 6.22-6.15 (m, 1H), 6.02-5.98 (m, 2H), 5.44-5.39 (m,
1H), 5.08 (d, J = 17.4 Hz, 1H), 4.97 (d, J = 10.2 Hz, 1H), 3.89
(dd, J = 10.8, 6.6 Hz, 1H), 3.71 (s, 3H), 2.53 (dd, J = 12.6, 6.6
Hz, 1H), 2.46-2.37 (m, 2H), 2.10 (dd, J = 12.6, 10.2 Hz, 1H),
1.55 (s, 9H), 1,39 (s, 9H). 13C NMR (150 MHz, Chloroform-d):
δ 173.1, 152.3, 142.2, 136.5, 135.0, 132.6, 128.5, 127.8, 122.7,
118.6, 116.6, 81.4, 80.3, 59.3, 52.1, 40.7, 35.2, 28.2. HRMS
(ESI) exact mass calculated for [M+H+] (C27H37N2O6): m/z
485.2646; found: 485.2674.
According to method B, flash column chromatography (SiO2: 5%
ethyl acetate in petroleum ether) provided this compound in 67%
yield (85.7 mg, 0.201 mmol) as foam solid.
IR (KBr) νꢀ=ꢀ2978, 2929, 1703, 1482, 1398, 1364, 1172, 1007,
893, 746. 1H NMR (600 MHz, Chloroform-d): δ 7.58 (bs, 1H),
7.20 (t, J = 7.2 Hz, 1H), 7.09 (d, J = 7.2 Hz, 1H), 7.01 (t, J = 7.2
Hz, 1H), 6.20 (dt, J = 17.4, 10.2 Hz, 1H), 6.07-6.02 (m, 2H),
5.51-5.46 (m, 1H), 5.08 (d, J = 16.8 Hz, 1H), 4.96 (d, J = 10.2
Hz, 1H)，3.73 (dd, J = 11.4, 7.8 Hz, 1H), 2.84 (td, J = 12.0, 5.4
Hz, 1H), 2.55-2.52 (m, 1H), 2.44 (dd, J = 13.8, 8.4 Hz, 1H),
2.04-1.95 (m, 2H), 1.55 (s, 9H), 1.47 (s, 9H). 13C NMR (150
MHz, Chloroform-d): δ 153.9, 152.4, 142.9, 136.6, 134.7,
128.7, 128.2, 123.1, 122.9, 116.2, 81.3, 79.9, 65.3, 45.8, 42.0,
41.3, 28.4, 28.3. HRMS (ESI) exact mass calculated for [M+H+]
(C25H35N2O4): m/z 427.2591; found: 427.2606.
4.2.33 Methyl 1-(2-phenylallyl) cyclopropane-1-carboxylate
(25)
According to method A, flash column chromatography (SiO2: 1%
ethyl acetate in petroleum ether) provided this compound in 52%
yield (33.7 mg, 0.156 mmol) as colorless oil.
4.2.30 Di-tert-butyl (3aS)-5-chloro-3a-((E)-penta-2,4-dien-1-
IR (KBr) νꢀ=ꢀ2941, 1766, 1723, 1445, 1355, 1212, 1152, 756,
701. 1H NMR (500 MHz, Chloroform-d): δ 7.44-7.42 (m, 2H),
7.36-7.33 (m, 2H), 7.31-7.29 (m, 1H), 5.37 (d, J = 1.0 Hz, 1H),
5.16 (d, J = 1.5 Hz, 1H), 3.66 (s, 3H), 2.86 (s, 2H), 1.30 (q, J =
7.0 Hz, 2H), 0.79 (q, J = 7.0 Hz, 2H). 13C NMR (125 MHz,
Chloroform-d): δ 175.5, 145.7, 141.9, 128.2, 127.4, 126.0,
113.1, 51.9, 37.6, 22.0, 15.4. HRMS (ESI) exact mass calculated
for [M+H+] (C14H17O2): m/z 217.1223; found: 217.1225.
yl)-2,3,3a,8a-tetrahydro
dicarboxylate (22)
pyrrolo[2,3-b]
indole-1,8-
According to method B, flash column chromatography (SiO2: 5%
ethyl acetate in petroleum ether) provided this compound in 45%
yield (62.2 mg, 0.135 mmol) as foam solid. mp: 89-91 oC.
IR (KBr) νꢀ=ꢀ2976, 2927, 1711, 1480, 1396, 1316, 1250, 1160,
1020, 891, 754. 1H NMR (600 MHz, Chloroform-d): δ 7.53 (bs,
1H), 7.16 (dd, J = 8.4, 1.8 Hz, 1H), 7.05 (d, J = 1.8 Hz, 1H), 6.20
(dt, J = 16.8, 10.2 Hz, 1H), 6.08-6.03 (m, 2H), 5.46-5.41 (m, 1H),
5.10 (d, J = 16.8 Hz, 1H), 4.98 (d, J = 10.2 Hz, 1H)，3.75 (dd, J
= 11.4, 7.2 Hz, 1H), 2.85 (td, J = 12.0, 5.4 Hz, 1H), 2.55-2.52 (m,
1H), 2.43 (dd, J = 13.8, 8.4 Hz, 1H), 1.99-1.96 (m, 2H), 1.54 (s,
9H), 1.46 (s, 9H). 13C NMR (150 MHz, Chloroform-d): δ 153.8,
152.1, 141.6, 136.4, 135.1, 128.2, 123.1, 116.6, 81.7, 80.1, 56.4,
Acknowledgments
Financial support was provided by the Chinese NSF (Nos.
21572140 and 21372151).
Ms Yanhong Song was thanked for use of NMR facility.
Reference

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