C(sp3)-H Azidation Reaction: A Protocol for Preparation of Aminals

Article abstract of DOI:10.1021/acs.joc.8b00235

We report a protocol for the synthesis of N,N- and N,O-aminals via direct azidation of sp³ C-H bonds of substrates with an α-nitrogen or α-oxygen atom. A broad range of tetrahydroisoquinolines, tetrahydro-β-carbolines, and cyclic benzyl ethers gave high yields under mild conditions. The protocol could be carried out on a gram scale without a decrease in the yield, and the aminal products could be readily transformed into complex aminals.

Full text of DOI:10.1021/acs.joc.8b00235

Subscriber access provided by UNIV OF DURHAM
C(sp3)–H Azidation Reaction: A Protocol for Preparation of Aminals
Jianyang Dong, Qing Xia, Changcun Yan, Hongjian Song, Yuxiu Liu, and Qingmin Wang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00235 • Publication Date (Web): 22 Mar 2018
Downloaded from http://pubs.acs.org on March 23, 2018
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 11
The Journal of Organic Chemistry
1
2
3
4
5
6
C(sp3)–H Azidation Reaction: A Protocol for Preparation of Aminals
7
8
9
†‡
Jianyang Dong,† Qing Xia,† Changcun Yan,† Hongjian Song,† Yuxiu Liu† and Qingmin Wang*
†State Key Laboratory of ElementoꢀOrganic Chemistry, Research Institute of ElementoꢀOrganic Chemistry, College of
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Chemistry, Nankai University, Tianjin 300071, People’s Republic of China
‡Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, People’s Republic of Chiꢀ
na
Supporting Information Placeholder
ABSTRACT: We report a protocol for the synthesis of N,Nꢀ
and N,Oꢀaminals via direct azidation of sp3 C–H bonds of subꢀ
strates with an αꢀnitrogen or αꢀoxygen atom. A broad range of
tetrahydroisoquinolines, tetrahydroꢀβꢀcarbolines, and cyclic
benzyl ethers gave high yields under mild conditions. The proꢀ
tocol could be carried out on a gram scale without a decrease in
the yield, and the aminal products could be readily transformed into complex aminals.
INTRODUCTION
Aminal structural units are present in numerous natural prodꢀ
ucts and functional materials and have attracted considerable
attention as building blocks for the synthesis of bioactive molꢀ
ecules, including drug candidates (Figure 1).1 For example, the
natural product evodiamine is an aminalꢀcontaining molecule
with antiꢀinflammatory, antiꢀobesity, and antitumor activiꢀ
ties.1a Several tetracyclic aminal compounds have been reportꢀ
ed to inhibit cholinesterase at micromolar concentrations.1b
Two aminal moieties are present in the communesins, which
have substantial cytotoxicity and insecticidal activity.1c Myꢀ
calamide A possesses strong immunosuppressive activities and
is considerably more potent than cyclosporine A.1d In addition,
aminalꢀcontaining molecules have found a wide range of apꢀ
plications in optoelectronic materials.1e
Scheme 1. General C–H Functionalization Methods for the
Synthesis of Aminals
derivatives.3 However, this oftenꢀmultistep strategy has a limꢀ
ited substrate scope. Formation of C–N bonds by means of
direct functionalization of C–H bonds is one of the most effiꢀ
cient and shortest routes to aminals.4 In 2008, an efficient
goldꢀcatalyzed procedure for the preparation of aminals was
developed by Manzo and coꢀworkers (Scheme 1a).4a More
versatile, Antilla’s group produced chiral N,Nꢀ and N,Oꢀ
aminals by means of Brønstedꢀacidꢀcatalyzed asymmetric
additions of nucleophiles to imines (Scheme 1b).4b–d,5 Recentꢀ
ly, Toste et al. reported that enantioselective C–N bondꢀ
forming reactions produce cyclic aminals from tetrahydroisoꢀ
quinolines (THIQs, Scheme 1c).4e,4f However, all these methꢀ
ods require prefunctionalization to generate Nꢀsubstituted or
Figure 1. Representative N,Nꢀ and N,Oꢀaminals.
Therefore, the development of efficient and convenient
methods for synthesizing aminals has attracted considerable
research effort.2 Aminals have been constructed by means of
Curtius and Hoffman rearrangements of protected amino acid
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 11
Nꢀprotected aminals, which hampers their differentiation and
Scheme 2. Reactions of Various Substituted NꢀAcyl THIQs
and THCsa
further elaboration. Therefore, a practical and direct C(sp3)–H
functionalization method for rapid preparation of unsubstituted
aminals would be highly desirable.
1
2
3
4
5
6
7
8
9
Herein, we report a method for the synthesis of unsubstitutꢀ
ed N,Nꢀ and N,Oꢀaminals by means of direct azidation of
THIQs, tetrahydroꢀβꢀcarbolines (THβCs), and cyclic benzyl
ethers (Scheme 1d). Our method not only affords the desired
products under mild conditions without the need for prefuncꢀ
tionalization but also does not require the use of expensive
metal catalysts. Moreover, the resulting aminals can be readily
transformed into complex aminals through azide chemistry.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
RESULTS AND DISCUSSION
Table 1. Optimization of azidation conditionsa
aReaction conditions, unless otherwise noted: 1 (0.3 mmol, 1
equiv), T+BF4– (1.2 equiv), trimethylsilylazide (1.2 equiv), and 4A
molecular sieves (20 mg) in CH3CN (3 mL) at rt under air. Isolatꢀ
ed yields are provided, unless noted otherwise. bReactions were
entry
oxidant
R1
solvent
yield
(%)b
89
c
performed on a 3 mmol scale. NMR yield. d1 (0.2 mmol, 1
equiv),T+BF4– (1.5 equiv), trimethylsilylazide (1.5 equiv). and 4A
molecular sieves (20 mg) in CH3CN (2 mL) at rt under air.
–
1
2
T+BF4
OBn
OBn
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMSO
DCM
DDQ
Na2S2O8
Ph3CClO4
Ph3CBF4
PIDA
29
NR
<5
19
<5
NR
73
68
50
32
<5
81
63
81
3
OBn
mates gave low yields (entries 7–11). Solvent optimization
confirmed CH3CN to be the ideal solvent (entries 12–15). We
were pleased to discover that the addition of 20 mg of 4A moꢀ
lecular sieves increased the yield to 92% (entry 16).
4
OBn
5
OBn
6
OBn
–
T+BF4
Me
With the optimized conditions in hand, we tested various
substituted Nꢀacyl THIQ and THβCs substrates (Scheme 2).
Generally, the electronic character and location of the substitꢀ
uent on the Nꢀacyl THIQ only slightly affected its reactivity,
and the desired products were obtained in good to excellent
yields (2a–i). A Cbzꢀprotected isoindoline could also be used
as a substrate, giving a 45% yield of 2j under the standard
conditions. Next, we turned our attention to azidation reactions
of THβCs substrates. αꢀSubstituted THβCs are present in nuꢀ
merous pharmacologically active alkaloids.7 However, to our
knowledge, introduction of an amine group at the αꢀposition of
THβCs by means of C–H functionalization has not been reꢀ
ported. Under the reaction conditions, the use of Cbzꢀprotected
THβC as substrate was tested; however, the reaction became
to be mess which may be affected by the unprotected NH of
indol substructure..Fortunately, we could get desired product
2k when this NH was protected by Ts group.8 We found that
both electronꢀrich and electronꢀdeficient THβCs tolerated the
standard azidation conditions, affording desired products 2l–q
in moderate yields. Note, however, that the reaction time had
to be extended to 48 h, perhaps because of the presence of the
Ts group, which reduced the electron density of the substrates.
Notably, similar yields were obtained for largeꢀscale (3 mmol)
reactions (see 2a and 2k).
7
–
8
T+BF4
OMe
–
9
T+BF4
OEt
–
10
11
12
13
14
15
T+BF4
T+BF4
T+BF4
T+BF4
T+BF4
T+BF4
OtBu
fluorenylmethyl
OBn
–
–
–
OBn
–
OBn
DCE
–
OBn
CHCl3
–
16c
T+BF4
OBn
92
CH3CN
(90)d
a
Reaction conditions: 1 (0.3 mmol, 1 equiv), oxidant (1.2 equiv),
and trimethylsilylazide (1.2 equiv) in CH3CN (3 mL) at rt under
air for 6 h. bNMR yield determined with 1,1,2,2ꢀtetrachloroethane
(0.3 mmol) as an internal standard; NR, no reaction; PIDA, iodoꢀ
c
benzene diacetate. Molecular sieves (4A, 20 mg) were added.
dIsolated yield.
We selected Nꢀacyl THIQs 1 and trimethylsilylazide as
model substrates for optimization of the azidation reaction
conditions (Table 1). When
we used 2,2,6,6ꢀ
tetramethylpiperidineꢀ1ꢀoxoammonium (T+BF4 ) as the oxiꢀ
dant and CH3CN as the solvent, reaction of the benzyl carbaꢀ
mate gave desired product 2 in 89% yield after 6 h at rt under
air (entry 1). Various oxidants were then screened; DDQ,
Na2S2O8, Ph3CClO4, Ph3CBF4, and PIDA6 either were less
effective than T+BF4– or were completely ineffective (entries
2–6). Then a variety of amide and carbamate derivatives of
THIQ were evaluated. The acetamide of THIQ did not react,
and the methyl, ethyl, tertꢀbutyl and fluorenylmethyl carba
–
We previously reported a photocatalytic strategy for syntheꢀ
sis of isochroman peroxyacetals through isochroman oxoꢀ
carbenium ion pairs intermediate, and similarly, we subjected
various isochroman derivatives to our azidation conditions to
synthesize unprotected N,Oꢀaminals (Scheme 3).9 Reactions of
a broad range of isochroman derivatives bearing either elecꢀ
tronꢀwithdrawing or electronꢀdonating functional groups
ACS Paragon Plus Environment

Page 3 of 11
The Journal of Organic Chemistry
copper iodide (0.1 equiv) in CH3CN (2 mL) was added at rt under
smoothly generated desired products 4a–i in good yields, and
b
–
Ar. Isolated yields are provided. T+BF4 (1.5 equiv), trimethylsiꢀ
1
2
3
4
5
6
7
8
the position of the substituents had little effect on the reaction
outcome. When fiveꢀ, sixꢀ, and sevenꢀmemberedꢀring cyclic
benzyl ethers were used as substrates, addition of a single azꢀ
ide group proceeded selectively to form 4j (71%), 4k (87%),
and 4l (42%), respectively. In addition to the cyclic benzyl
ethers, xanthene was also a suitable substrate, generating 4m
in 92% yield.
lylazide (1.5 equiv).
To demonstrate the practicality of our method, we syntheꢀ
sized tricyclic compound 7, the skeleton of which is common
in optoelectronic materials,1e starting from 6 in two steps (46%
overall yield, Scheme 5a). The iodo group of 7 can be used for
further functionalization reactions to afford compounds with
potential utility as optoelectronic materials. In addition, we
carried out Staudinger reactions of 2a and 2k in the absence of
water to obtain iminophosphoranes 8 (86% yield) and 10 (84%
yield) (Scheme 5b,c). Iminophosphoranes, which like azaꢀ
ylides, are important synthetic intermediates, and the azaꢀ
Wittig reaction is one of the most useful reactions for the synꢀ
thesis of molecules with nitrogenꢀcontaining functionalities.11
Therefore, we used this strategy to produce aminals 9 (45%
yield) and 11 (62% yield) by means of a oneꢀpot threeꢀstep trꢀ
Scheme 3. Azidation Reactions of Cyclic Benzyl Ethersa
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 5. Synthetic Applications of Unprotected Aminals
aReaction conditions: 3 (0.3 mmol, 1 equiv), T+BF4– (1.2 equiv),
trimethylsilylazide (1.2 equiv), and 4A molecular sieves (20 mg)
in CH3CN (3 mL) at rt. Isolated yields are provided.
We found that some of the unprotected N,Nꢀ or N,Oꢀaminal
products were unstable on silica gel, which reduced the isolatꢀ
ed yields (2q and 4a) or prevented us from isolating any prodꢀ
uct at all (2h and 2i). Therefore, we wondered whether these
unstable products could be subjected to a click reaction in the
same pot as the azidation reaction. Copperꢀcatalyzed alkyneꢀ
azide cycloaddition (click reaction) is a highly versatile, regiꢀ
oselective method for synthesizing 1,4ꢀdisubstituted 1,2,3ꢀ
triazoles under mild reaction conditions and has found numerꢀ
ous applications in medicinal, bioorganic, and materials chemꢀ
istry.10 In this study, we conducted some oneꢀpot transforꢀ
mations involving azidation and subsequent click reaction, and
we obtained moderate to good yields of 5a–d (Scheme 4).
These transformations demonstrate the utility of our azidation
reaction for synthesizing complex molecules containing amiꢀ
nals.
ansformation (Scheme 5b,c). In short, the unprotected N,Nꢀ
aminals generated by the protocol described herein are promisꢀ
ing candidates for the synthesis of various more complex amiꢀ
nals.
Scheme 6. RadicalꢀTrapping Study
Scheme 4. OneꢀPot Synthesis of Triazolesa
In the TEMPO salt mediated CꢀH oxidations, there are two
possible mechanisms for the oxidation step: a hydride transfer
mechanism and a singleꢀelectron transfer mechanism, which
has been proposed to form an Nꢀcentered radical cation interꢀ
mediate.12 In order to gain some mechanistic insight into the
present azidation reaction, we conducted the radical inhibition
experiment (Scheme 6). Under the standard conditions, when
TEMPO ( 2,2,6,6ꢀtetramethylpiperidineꢀ1ꢀoxyl) was added to
the system, the yield of product 2a was found to be almost the
same as that for the model reaction (eq 1). On the contrary, the
presence of BHT (2,6ꢀdiꢀtertꢀbutylꢀ4ꢀmethylphenol) led to a
dramatically lower yield of the desired product (from 92 to
34%). This result suggested that a rapid radical cation might
aReaction conditions, unless otherwise noted: 1h, 1i, 1q or 3a (0.3
–
mmol, 1 equiv), T+BF4 (1.2 equiv), trimethylsilylazide (1.2
equiv), and 4A molecular sieves (20 mg) in CH3CN (3 mL) at rt
under air. After 1h, 1i, 1q, or 3a was completely consumed, a
solution of phenylacetylene (1.5 equiv), DIPEA (1.5 equiv), and
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 11
be involved in the reaction.13 However, we cannot exclude a
5.22 (s, 2H), 4.32 – 3.96 (m, 1H), 3.55 – 3.30 (m, 1H), 2.99 –
hydride transfer mechanism at this time.14 We would like to
propose a plausible mechanism of azidation reaction in
Scheme 7. Following oxidation with T+BF4–, 1a forms an
iminium cation intermediate A through the singleꢀelectron
transfer or hydride transfer process. And then a nucleophilic
addition of TMSN3 to the iminium cation gives the desired
product 2a.
2.75 (m, 2H); 13C NMR (100 MHz, CDCl3, rotamers seen) δ
155.8 and 155.0, 136.2 and 136.0, 135.0 and 134.8, 131.8 and
131.6, 129.0, 128.7, 128.5, 128.2, 128.0, 127.0, 70.5, 68.3 and
68.1, 39.2 and 38.5, 28.3 and 28.2; IR (neat) υmax = 3032,
2097 (N3), 1699, 1418, 1230 cmꢀ1; HRMS (ESI) calcd for
C17H16NO2 [M – N3]+ 266.1176, found 266.1177; Rf 0.48 (Peꢀ
troleum ether/EtOAc, 20/1).
1
2
3
4
5
6
7
8
Benzyl
1ꢀazidoꢀ8ꢀbromoꢀ3,4ꢀdihydroisoquinolineꢀ2(1H)ꢀ
Scheme 7. Proposed Mechanism
carboxylate (2b). According to the general procedure A. Colꢀ
9
1
orless oil (108.8 mg, 94%); H NMR (400 MHz, CDCl3, rotaꢀ
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
mers seen) δ 7.49 (dd, J = 7.2, 2.0 Hz, 1H), 7.46 – 7.30 (m,
5H), 7.18 – 7.06 (m, 2H), 6.91 and 6.79 (s, 1H), 5.27 and 5.24
(s, 2H), 4.22 – 3.94 (m, 1H), 3.66 – 3.40 (m, 1H), 3.02 – 2.80
(m, 2H); 13C NMR (100 MHz, CDCl3, rotamers seen) δ 156.2
and 155.2, 138.1 and 137.9, 136.5 and 136.3, 132.1 and 131.9,
130.6 and 130.5, 129.2, 128.9, 128.8, 128.7, 128.4, 124.3, 71.5
and 71.3, 68.7 and 68.6, 39.3 and 38.7, 28.9 and 28.7; IR
(neat) υmax = 3032, 2099 (N3), 1716, 1699, 1473, 1418, 1205,
696 cmꢀ1; HRMS (ESI) calcd for C17H15BrN4NaO2 [M + Na]+
409.0271, found 409.0264; Rf 0.36 (Petroleum ether/EtOAc,
20/1).
In conclusion, we have developed a protocol for the synthesis
of N,Nꢀ and N,Oꢀaminals by means of direct azidation of sp3
C–H bonds of substrates with an αꢀnitrogen or αꢀoxygen atom.
The protocol is applicable to a wide range of THIQs, THβCs,
and cyclic benzyl ethers, and the resulting aminals can readily
be converted to more complex aminals by means of azide
chemistry. This is the first report of the introduction of an
amine group at the αꢀposition of THβCs by means of C–H
functionalization. The potential applications of this interesting
synthetic methodology are currently under investigation in our
laboratory.
Benzyl
1ꢀazidoꢀ7ꢀnitroꢀ3,4ꢀdihydroisoquinolineꢀ2(1H)ꢀ
carboxylate (2c). According to the general procedure A. Colꢀ
1
orless oil (96.4 mg, 91%); H NMR (400 MHz, CDCl3, rotaꢀ
mers seen) δ 8.20 (d, J = 14.4 Hz, 1H), 8.12 (d, J = 8.2 Hz,
1H), 7.63 – 7.30 (m, 6H), 6.80 and 6.65 (s, 1H), 5.51 – 4.78
(m, 2H), 4.45 – 4.12 (m, 1H), 3.52 – 3.30 (m, 1H), 3.20 ꢀ 2.80
(m, 2H); 13C NMR (100 MHz, CDCl3, rotamers seen) δ 156.1
and 155.0, 147.3, 142.9 and 142.7, 136.2 and 135.8, 134.1 and
133.8, 130.6 and 130.4, 129.2, 128.8, 124.0, 123.9, 70.1, 69.2
and 68.9, 38.6 and 38.0, 29.0; IR (neat) υmax = 3065, 2098
(N3), 1699, 1540, 1418, 1222 cmꢀ1; HRMS (ESI) calcd for
C17H15N5NaO4 [M + Na]+ 376.1016, found 376.1011; Rf 0.38
(Petroleum ether/EtOAc, 10/1).
Benzyl 1ꢀazidoꢀ7ꢀtrifluoromethylꢀ3,4ꢀdihydroisoquinolineꢀ
2(1H)ꢀcarboxylate (2d). According to the general procedure
A. Colorless oil (102.6 mg, 91%); 1H NMR (400 MHz, CDCl3,
rotamers seen) δ 7.64 – 7.47 (m, 2H), 7.46 – 7.31 (m, 5H),
7.28 (d, J = 8.0 Hz, 1H), 6.74 and 6.59 (s, 1H), 5.29 – 5.17 (m,
2H), 4.42 – 4.05 (m, 1H), 3.56 – 3.29 (m, 1H), 3.06 – 2.77 (m,
2H); 13C NMR (100 MHz, CDCl3, rotamers seen) δ 156.2 and
155.1, 139.5 and 139.3, 136.3 and 136.0, 133.2 and 132.9,
130.0 (q, J = 18.0 Hz), 129.2, 129.1 and 129.0, 128.7, 126.0
(q, J = 4.0 Hz), 125.5(q, J = 4.0 Hz), 124.3 (q, J = 270.0), 70.3,
EXPERIMENTAL SECTION
General Method and Materials. All reagents were used as
received. Acetonitrile was distilled on phosphorus pentoxide.
1H and 13C Nuclear Magnetic Resonance (NMR) spectra were
recorded on Bruker Avance 400 Ultrashield NMR spectromeꢀ
ters. Chemical shifts (δ) were given in parts per million (ppm)
and were measured downfield from internal tetramethylsilane.
Highꢀresolution mass spectrometry (HRMS) data were obꢀ
tained on an FTICRꢀMS instrument (Ionspec 7.0 T). The meltꢀ
ing points were determined on an Xꢀ4 microscope melting
point apparatus and are uncorrected. Conversion was moniꢀ
tored by thin layer chromatography (TLC). Flash column
chromatography was performed over silica gel (100ꢀ200
–
mesh). 1a-j and T+BF4 were synthesized with a previously
69.0 and 68.7, 39.0 and 38.3, 28.8 and 28.7; IR (neat) υmax
=
described procedure.12aꢀc 3a-l were synthesized with a previꢀ
3048, 2100 (N3), 1716, 1653, 1336, 1126 cmꢀ1; HRMS (ESI)
calcd for C18H15F3N4NaO2 [M + Na]+ 399.1039, found
399.1034; Rf 0.36 (Petroleum ether/EtOAc, 15/1).
ously described procedure.9
Synthesis of Compouds 2a-g and 2j. General Procedure
A. An ovenꢀdried Schlenk tube was charged with substrate 1
(0.3 mmol), T+BF4– (87.5 mg, 0.36 mmol) and 4A molecular
sieves (20 mg), and then dry acetonitrile (3.0 mL), trimethylsiꢀ
lazide (48 ꢁL, 0.36 mmol) was added by syringe. The reaction
mixture was stirred at room temperature for 4ꢀ12 h until the
consumption of the starting material, indicated by TLC. The
reaction mixture was concentrated in vacuum to give the crude
product, which was purified by common column chromatogꢀ
raphy (SiO2) to give the desired compounds.
Benzyl
1ꢀazidoꢀ7ꢀbromoꢀ3,4ꢀdihydroisoquinolineꢀ2(1H)ꢀ
carboxylate (2e). According to the general procedure A. Colꢀ
1
orless oil (115.0 mg, >99%); H NMR (400 MHz, CDCl3,
rotamers seen) δ 7.53 – 7.28 (m, 7H), 7.03 (d, J = 8.2 Hz, 1H),
6.63 and 6.48 (s, 1H), 5.30 – 5.17 (m, 2H), 4.35 – 4.01 (m,
1H), 3.51 – 3.26 (m, 1H), 2.94 – 2.66 (m, 2H); 13C NMR (100
MHz, CDCl3, rotamers seen) δ 156.0 and 155.0, 136.3 and
136.0, 134.2, 134.0, 132.4, 131.3, 131.0 and 130.9, 129.1,
129.0, 128.6, 120.7, 70.1, 68.8 and 68.6, 39.2 and 38.5,
28.3; IR (neat) υmax = 3032, 2945, 2099 (N3), 1716, 1699,
1419, 1291, 1099, 697 cmꢀ1; HRMS (ESI) calcd for
C17H15BrNO2 [M – N3]+ 346.0260, found 346.0258; Rf 0.32
(Petroleum ether/EtOAc, 15/1).
Benzyl 1ꢀazidoꢀ3,4ꢀdihydroisoquinolineꢀ2(1H)ꢀcarboxylate
(2a). According to the general procedure A. Colorless oil
(83.2 mg, 90%); 1H NMR (400 MHz, CDCl3, rotamers seen) δ
7.45 – 7.22 (m, 8H), 7.19 ꢀ7.11 (m, 1H), 6.65 and 6.50 (s, 1H),
ACS Paragon Plus Environment

Page 5 of 11
The Journal of Organic Chemistry
Benzyl 1ꢀazidoꢀ6ꢀchlorineꢀ3,4ꢀdihydroisoquinolineꢀ2(1H)ꢀ
Benzyl 7ꢀbromoꢀ9ꢀtosylꢀ1,3,4,9ꢀtetrahydroꢀ2Hꢀpyrido[3,4ꢀ
1
2
carboxylate (2f). According to the general procedure A. Colꢀ
b]indoleꢀ2ꢀcarboxylate (1l). According to the general proceꢀ
1
1
orless oil (88.2 mg, 86%); H NMR (400 MHz, CDCl3, rotaꢀ
dure B. White solid (0.47 g, 87%); M.p. = 48 – 50 °C. H
mers seen) δ 7.35 (m, 5H), 7.27 – 7.18 (m, 2H), 7.15 (s, 1H),
6.63 and 6.48 (s, 1H), 5.23 (s, 2H), 4.38 – 3.98 (m, 1H), 3.55 –
3.26 (m, 1H), 2.99 – 2.65 (m, 2H); 13C NMR (100 MHz,
CDCl3, rotamers seen) δ 156.0 and 155.0, 137.1 and 136.9,
136.2 and 136.0, 134.9, 130.6 and 130.4, 129.6, 129.1, 129.0,
128.9, 128.8, 128.5, 127.5, 70.1, 68.7 and 68.4, 38.9 and 38.2,
28.5 and 28.4; IR (neat) υmax = 3101, 3032, 2098 (N3), 1749,
1716, 1495, 1457, 1338 1230, 696 cmꢀ1; HRMS (ESI) calcd
for C18H18ClNNaO3 [M – N3 + OMe + Na]+ 354.0867, found
354.0862; Rf 0.50 (Petroleum ether/EtOAc, 15/1).
NMR (400 MHz, CDCl3, rotamers seen) δ 8.29 (s, 1H), 7.83 –
7.52 (m, 2H), 7.46 – 7.26 (m, 6H), 7.26 – 7.08 (m, 2H), 6.99
(d, J = 7.6 Hz, 1H), 5.18 (s, 2H), 4.93 (s, 2H), 3.75 (s, 2H),
2.64 (s, 2H), 2.28 (s, 3H); 13C NMR (100 MHz, CDCl3, rotaꢀ
mers seen) δ 155.4, 145.3, 136.6, 136.5, 135.2, 132.1 and
131.5, 130.1, 128.6, 128.3, 128.2, 128.0, 126.8, 126.5 and
126.4, 119.5, 118.1, 117.2, 116.7, 67.5, 43.5 and 43.3, 41.2
and 41.0, 21.6, 21.4 and 20.9; HRMS (ESI) calcd for
C26H24BrN2SO4 [M + H]+ 541.0614, found 541.0617; Rf 0.40
(Petroleum ether/EtOAc, 7/1).
Benzyl 7ꢀchloroꢀ9ꢀtosylꢀ1,3,4,9ꢀtetrahydroꢀ2Hꢀpyrido[3,4ꢀ
b]indoleꢀ2ꢀcarboxylate (1m). According to the general proceꢀ
dure B. White solid (0.44 g, 88%); M.p. = 46 – 47°C. 1H NMR
(400 MHz, CDCl3, rotamers seen) δ 8.15 (s, 1H), 7.75 (s, 1H),
7.61 (d, J = 5.2 Hz, 1H), 7.45 – 7.30 (m, 5H), 7.28 – 7.15 (m,
3H), 7.03 (s, 1H), 5.18 (s, 2H), 4.95 (s, 2H), 3.77 (s, 2H), 2.67
(s, 2H), 2.40 – 2.24 (m, 3H); 13C NMR (100 MHz, CDCl3,
rotamers seen) δ 155.4, 145.4, 136.6, 136.3, 135.2, 132.1
and 131.6, 130.5, 130.1, 128.6, 128.2, 128.0, 127.9, 126.6
and 126.4, 124.1, 119.1, 117.2 and 116.6, 114.4, 67.5, 43.5
and 43.3, 41.2 and 41.0, 21.6, 21.4 and 20.9; HRMS (ESI)
calcd for C26H24ClN2SO4 [M + H]+ 495.1140, found 495.1134;
Rf 0.52 (Petroleum ether/EtOAc, 5/1).
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Benzyl
1ꢀazidoꢀ6ꢀbromoꢀ3,4ꢀdihydroisoquinolineꢀ2(1H)ꢀ
carboxylate (2g). According to the general procedure A. Colꢀ
1
orless oil (99.6 mg, 86%); H NMR (400 MHz, CDCl3, rotaꢀ
mers seen) δ 7.47 – 7.28 (m, 7H), 7.21 – 7.06 (m, 1H), 6.61
and 6.48 (s, 1H), 5.22 (s, 2H), 4.34 – 4.01 (m, 1H), 3.52 – 3.25
(m, 1H), 2.96 – 2.69 (m, 2H); 13C NMR (100 MHz, CDCl3,
rotamers seen) δ 155.6 and 154.7, 137.1 and 136.9, 135.9 and
135.7, 131.8 and 131.6, 130.8 and 130.6, 130.1, 129.5, 128.7,
128.6, 128.5, 128.2, 122.8, 69.8, 68.4 and 68.1, 38.6 and 37.9,
28.1 and 28.0; IR (neat) υmax = 3033, 2098 (N3), 1699, 1653,
1419, 1220, 697 cmꢀ1; HRMS (ESI) calcd for C17H15BrNO2 [M
– N3]+ 346.0260, found 346.0260; Rf 0.50 (Petroleum
ether/EtOAc, 15/1).
Benzyl 6ꢀfluoroꢀ9ꢀtosylꢀ1,3,4,9ꢀtetrahydroꢀ2Hꢀpyrido[3,4ꢀ
b]indoleꢀ2ꢀcarboxylate (1n) (0.49 g, 90%); According to the
Benzyl 1ꢀ azidoisoindolineꢀ2ꢀcarboxylate (2j). According to
1
the general procedure A. Colorless oil (39.7 mg, 45%); H
1
general procedure B. White solid, M.p. = 120 – 121°C. H
NMR (400 MHz, CDCl3, rotamers seen) δ 7.49 – 7.25 (m,
9H), 6.48 and 6.37 (s, 1H), 5.44 – 5.12 (m, 2H), 4.76 and 4.74
(s, 2H); 13C NMR (100 MHz, CDCl3, rotamers seen) δ 155.6
and 154.9, 137.3 and 137.1, 136.6 and 136.5, 136.4 and 136.0,
130.3, 129.2, 129.0, 128.9, 128.8, 128.7, 124.5 and 124.4,
123.4 and 123.3, 79.4 and 78.7, 68.5 and 68.2, 52.5 and 52.1;
IR (neat) υmax = 3012, 2101 (N3), 1716, 1699, 1558, 1541,
1362, 1107, 751 cmꢀ1; HRMS (ESI) m/z calcd for C16H14NO2
[M – N3]+ 252.1019, found 252.1027; Rf 0.46 (Petroleum
ether/EtOAc, 15/1).
Synthesis of Compouds 1k-q. General Procedure B. To a
solution of Cbzꢀprotected tetrahydroꢀβꢀcarbolines (THCs,
1mmol, 1 equiv.) in CH3CN (20 mL) was added sodium hyꢀ
dride (48 mg, 2 equiv.) under ice bath conditions. The reaction
was stirred for 30 min, and then, tosyl chloride (229 mg, 1.2
equiv.) was added slowly. The mixture was stirred for 10 min
at 0 ºC and then 4 h at rt. The reaction was quenched with
water (15 mL) under ice bath conditions followed by extracꢀ
tion with CH2Cl2 (3×15 mL).The combined organic phase was
washed with brine (30 mL), then dried over MgSO4 and conꢀ
centrated. The crude product was purified by common column
chromatography (SiO2) to give the desired compounds.
NMR (400 MHz, CDCl3, rotamers seen) δ 8.07 (dd, J = 9.2,
4.4 Hz, 1H), 7.74 (d, J = 6.0 Hz, 1H), 7.58 (d, J = 6.8 Hz,
1H), 7.44 – 7.28 (m, 5H), 7.22 (d, J = 5.6 Hz,, 1H), 7.07 –
6.94 (m, 3H), 5.19 (s, 2H), 4.97 (s, 2H), 3.78 (s, 2H), 2.66
(s, 2H), 2.38 – 2.25 (m, 3H).;
13C NMR (100 MHz, CDCl3,
rotamers seen) δ 159.8 (d, J = 240.0 Hz), 155.4, 145.2, 136.5,
135.2, 133.4 and 132.8, 132.3, 130.7 and 130.6, 130.0, 128.6,
128.2, 128.0, 126.6 and 126.4, 117.5 and 116.8, 115.4 and
115.3, 112.3 (d, J = 20.0 Hz) , 104.2 (d, J = 20.0 Hz), 67.5,
43.6 and 43.5, 41.2 and 41.0, 21.6, 21.1 and 21.0; HRMS
(ESI) calcd for C26H24FN2SO4 [M + H]+ 479.1435, found
479.1432; Rf 0.55 (Petroleum ether/EtOAc, 5/1).
Benzyl 6ꢀchloroꢀ9ꢀtosylꢀ1,3,4,9ꢀtetrahydroꢀ2Hꢀpyrido[3,4ꢀ
b]indoleꢀ2ꢀcarboxylate (1o). According to the general proceꢀ
1
dure B. White solid (0.39 g, 84%); M.p. = 54 – 56 °C. H
NMR (400 MHz, CDCl3, rotamers seen) δ 7.90 (d, J = 8.8 Hz,
1H), 7.59 (d, J = 5.6 Hz, 1H), 7.44 (d, J = 6.0 Hz, 1H), 7.32 –
7.15 (m, 6H), 7.14 – 7.05 (m, 2H), 6.87 (d, J = 6.0 Hz, 1H),
5.04 (s, 2H), 4.82 (s, 2H), 3.63 (s, 2H), 2.51 (s, 2H), 2.16 and
2.19 (s, 3H); 13C NMR (100 MHz, CDCl3, rotamers seen) δ
155.4, 145.3, 136.5, 135.1, 134.4, 133.1 and 132.5, 130.7,
130.1, 129.5, 128.6, 128.2, 128.0, 126.6 and 126.4, 124.8,
118.2, 117.0 and 116.4, 115.3, 67.5, 43.6 and 43.3, 41.2
and 41.0, 21.6, 21.4 and 20.9; HRMS (ESI) calcd for
C26H24ClN2SO4 [M + H]+ 495.1140, found 495.1144; Rf 0.60
(Petroleum ether/EtOAc, 5/1).
Benzyl 9ꢀtosylꢀ1,3,4,9ꢀtetrahydroꢀ2Hꢀpyrido[3,4ꢀb]indoleꢀ
2ꢀcarboxylate (1k). According to the general procedure B.
1
White solid (0.39 g, 85%); M.p. = 114 – 115 °C. H NMR
(400 MHz, CDCl3, rotamers seen) δ 8.12 (d, J = 8.0 Hz, 1H),
7.81 – 7.55 (m, 2H), 7.47 – 7.26 (m, 7H), 7.23 – 7.17 (m, 2H),
6.99 (d, J = 8.0 Hz, 1H), 5.19 (s, 2H), 4.99 (s, 2H), 3.77 (s,
2H), 2.69 (s, 2H), 2.27 (s, 3H); 13C NMR (100 MHz, CDCl3,
rotamers seen) δ 155.5, 145.0, 136.7, 136.1, 135.5, 131.5
and 130.9, 130.0, 129.5, 128.6, 128.2, 128.0, 126.4, 124.7,
123.6, 118.4, 117.6 and 117.1, 114.3, 67.5, 43.6 and 43.4,
Benzyl 6ꢀbromoꢀ9ꢀtosylꢀ1,3,4,9ꢀtetrahydroꢀ2Hꢀpyrido[3,4ꢀ
b]indoleꢀ2ꢀcarboxylate (1p). According to the general proceꢀ
1
dure B. White solid (0.49 g, 90%); M.p. = 135 – 136 °C. H
NMR (400 MHz, CDCl3, rotamers seen) δ 7.98 (d, J = 8.8 Hz,
1H), 7.79 – 7.52 (m, 2H), 7.48 – 7.28 (m, 7H), 7.20 (s, 1H),
7.00 (s, 1H), 5.19 (s, 2H), 4.97 (s, 2H), 3.76 (s, 2H), 2.63 (s,
2H), 2.28 (s, 3H); 13C NMR (100 MHz, CDCl3, rotamers seen)
41.3 and 41.1, 21.5, 21.1
; HRMS (ESI) calcd for
C26H25N2SO4 [M + H]+ 461.1530, found 461.1532; Rf 0.32
(Petroleum ether/EtOAc, 10/1).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 11
δ
155.4, 145.3, 136.5, 135.1, 134.8, 133.0 and 132.3, 131.2, and 116.7, 67.3, 67.2 and 66.1, 36.1 and 35.7, 20.7, 20.0
1
2
3
4
5
6
7
8
130.1, 128.6, 128.2, 128.0, 127.4, 126.6 and 126.4, 121.3,
117.1 and 116.9, 116.2, 115.7, 67.6, 43.5 and 43.3, 41.2
and 41.1, 21.6, 21.4 and 20.9; HRMS (ESI) calcd for
C26H24BrN2SO4 [M + H]+ 541.0614, found 541.0612; Rf 0.30
(Petroleum ether/EtOAc, 7/1).
and 19.6; IR (neat) υmax = 3056, 2918, 2106 (N3), 1716,
1507, 1457, 1418, 1170, 738, 582 cmꢀ1; HRMS (ESI) calcd for
C26H22ClN2SO4 [M – N3]+ 539.0458, found 539.0461; Rf 0.32
(Petroleum ether/EtOAc, 10/1).
Benzyl
1ꢀazidoꢀ7ꢀchloroꢀ9ꢀtosylꢀ1,3,4,9ꢀtetrahydroꢀ2Hꢀ
pyrido[3,4ꢀb]indoleꢀ2ꢀcarboxylate (2m). According to the
general procedure C. White solid (80.3 mg, 75%); M.p. = 52 –
53°C. H NMR (400 MHz, CDCl3 rotamers seen) δ 7.97 (s,
Benzyl
6ꢀmethoxyꢀ9ꢀtosylꢀ1,3,4,9ꢀtetrahydroꢀ2Hꢀ
pyrido[3,4ꢀb]indoleꢀ2ꢀcarboxylate (1q). According to the genꢀ
eral procedure B. Yellow solid (0.46 g, 94%); M.p. = 198 –
200 °C. 1H NMR (400 MHz, CDCl3, rotamers seen) δ 8.01 (d,
J = 8.8 Hz, 1H), 7.72 (s, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.47 –
7.30 (m, 5H), 7.19 (d, J = 5.2 Hz, 1H), 6.99 (d, J = 8.0 Hz,
1H), 6.90 (dd, J = 8.8, 5.2 Hz, 1H), 6.78 (s, 1H), 5.19 (s, 2H),
4.96 (s, 2H), 3.81 (s, 3H), 3.76 (s, 2H), 2.66 (s, 2H), 2.38 –
3.24 (m, 3H); 13C NMR (100 MHz, CDCl3, rotamers seen) δ
156.7, 155.5, 144.8, 136.6, 135.3, 132.2, 131.7, 130.6,
129.9, 128.6, 128.2, 128.0, 126.5 and 126.3, 117.8 and
117.1, 115.3, 113.1, 101.3, 67.5, 55.7, 43.7 and 43.5, 41.3
and 41.1, 21.6, 21.1; HRMS (ESI) calcd for C27H27N2SO5 [M
1
1H), 7.67 (d, J = 7.2 Hz, 1H), 7.57 (d, J = 7.2 Hz, 1H), 7.38
– 7.19 (m, 6H), 7.17 – 7.04 (m, 3H), 6.98 (d, J = 7.2 Hz,
1H), 5.29 – 5.07 (m, 2H), 4.31 (dd, J = 51.6, 8.8 Hz, 1H),
3.37 – 3.16 (m, 1H), 2.53 (dd, J = 30.8, 15.2 Hz, 2H), 2.19
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(s, 3H);
13C NMR (100 MHz, CDCl3, rotamers seen) δ 155.5
and 154.4, 145.6, 136.8 and 136.7, 136.0 and 135.8, 135.2,
132.0 and 131.9, 130.9 and 130.4, 130.2, 128.8, 128.6,
128.5, 128.4, 128.3, 126.9, 126.7, 124.7, 120.3 and 120.2,
120.1, 119.7, 115.0, 68.4 and 68.3, 67.3, 37.3 and 36.9,
21.7, 21.2 and 20.8; IR (neat) υmax = 3033, 2105 (N3), 1699,
1684, 1497, 1457, 1221, 734, 583 cmꢀ1; HRMS (ESI) calcd for
C26H22ClN2SO4 [M – N3]+ 493.0983, found 493.0984; Rf 0.36
(Petroleum ether/EtOAc, 15/1).
+
H]+ 491.1642, found 491.1635; Rf 0.28 (Petroleum
ether/EtOAc, 10/1).
Synthesis of Compouds 2k-q. General Procedure C. An
ovenꢀdried Schlenk tube was charged with substrate 1 (0.2
mmol), T+BF4– (73 mg, 0.30 mmol) and 4A molecular sieves
(20 mg), and then dry acetonitrile (2.0 mL), trimethylsilazide
(40 ꢁL, 0.30 mmol) was added by syringe. The reaction mixꢀ
ture was stirred at room temperature for 48 h until the conꢀ
sumption of the starting material, indicated by TLC. The reacꢀ
tion mixture was concentrated in vacuum to give the crude
product, which was purified by common column chromatogꢀ
raphy (SiO2) to give the desired compounds.
Benzyl
1ꢀazidoꢀ6ꢀfluoroꢀ9ꢀtosylꢀ1,3,4,9ꢀtetrahydroꢀ2Hꢀ
pyrido[3,4ꢀb]indoleꢀ2ꢀcarboxylate (2n). According to the genꢀ
eral procedure C. White solid (72.7 mg, 70%); M.p. = 46 – 47
1
°C. H NMR (400 MHz, CDCl3, rotamers seen) δ 8.07 – 7.96
(m, 1H), 7.76 (d, J = 7.6 Hz, 1H), 7.65 (d, J = 8.0 Hz, 1H),
7.50 – 7.29 (m, 6H), 7.18 (d, J = 7.6 Hz, 1H), 7.11 – 6.96
(m, 3H), 5.40 – 5.20 (m, 2H), 4.42 (ddd, J = 52.0, 13.2, 5.2
Hz, 1H), 3.49 – 3.28 (m, 1H), 2.79 – 2.51 (m, 2H), 2.30 (s,
3H).;
13C NMR (100 MHz, CDCl3, rotamers seen) δ 161.1 and
Benzyl 1ꢀazidoꢀ9ꢀtosylꢀ1,3,4,9ꢀtetrahydroꢀ2Hꢀpyrido[3,4ꢀ
b]indoleꢀ2ꢀcarboxylate (2k). According to the general proceꢀ
158.7 (d, J = 240.0 Hz), 155.5 and 154.3, 145.3, 135.9 and
135.8, 135.2, 132.8 and 132.7, 132.0, 131.5, 130.0, 129.5
and 129.4, 128.7, 128.5, 128.4, 128.2, 126.8, 126.6, 120.2
and 119.9, 116.2 and 116.1, 114.1 and 113.9 (d, J = 24.0
Hz), 105.2 and 105.0 (d, J = 24.0 Hz), 68.4 and 68.2, 67.3,
37.2 and 36.8, 21.6, 21.1 and 20.7; IR (neat) υmax = 3032,
2104 (N3), 1716, 1699, 1418, 1223, 664 cmꢀ1; HRMS (ESI)
calcd for C26H22FN2SO4 [M – N3]+ 477.1279, found 477.1285;
Rf 0.30 (Petroleum ether/EtOAc, 15/1).
1
dure C. White solid (75.2 mg, 75%); M.p. = 46 – 48 °C. H
NMR (400 MHz, CDCl3, rotamers seen) δ 1H NMR (400
MHz, CDCl3) δ 8.03 (d, J = 7.6 Hz, 1H), 7.75 (d, J = 7.6
Hz, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.46 – 7.29 (m, 7H), 7.26
– 7.16 (m, 2H), 7.13 (d, J = 7.6 Hz, 1H), 7.03 (d, J = 8.0
Hz, 1H), 5.37 – 5.08 (m, 2H), 4.38 (ddd, J = 54.0, 13.0, 5.2
Hz, 1H), 3.50 – 3.23 (m, 1H), 2.83 – 2.53 (m, 2H), 2.25 (s,
3H);
13C NMR (100 MHz, CDCl3, rotamers seen) δ 155.5 and
Benzyl
1ꢀazidoꢀ6ꢀchloroꢀ9ꢀtosylꢀ1,3,4,9ꢀtetrahydroꢀ2Hꢀ
154.4, 145.1, 136.5 and 136.4, 136.0 and 135.8, 135.4,
130.2, 129.9, 129.7 and 129.6, 128.7, 128.5, 128.4, 128.2,
126.8, 126.6, 126.1 and 126.0, 123.9, 120.4 and 120.0,
119.4 and 119.3, 114.8, 114.6 and 114.3, 68.3 and 68.2,
pyrido[3,4ꢀb]indoleꢀ2ꢀcarboxylate (2o). According to the genꢀ
eral procedure C. White solid (81.3 mg, 76%); M.p. = 64 – 66
1
°C. H NMR (400 MHz, CDCl3, rotamers seen) δ 8.08 – 7.93
(m, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.67 (d, J = 8.0 Hz, 1H),
,
67.5, 37.3 and 36.9, 21.6, 21.2 and 20.8; IR (neat) υmax
=
7.53 – 7.16 (m, 9H), 7.10 (d, J = 8.0 Hz, 1H), 5.44 – 5.09 (m,
2H), 4.42 (ddd, J = 52.4, 13.2, 5.2 Hz, 1H), 3.59 – 3.23 (m,
1H), 2.93 – 2.50 (m, 2H), 2.32 (s, 3H); 13C NMR (100 MHz,
CDCl3, rotamers seen) δ 156.0 and 154.8, 145.9, 136.3 and
136.2, 135.6, 135.3 and 135.2, 132.2, 131.7, 130.5, 130.3,
130.0, 129.2, 129.0, 128.9, 128.8, 127.3, 127.1, 126.7 and
126.6, 120.2 and 119.8, 119.6 and 119.5, 116.4, 68.9 and 68.8,
3032, 2102 (N3), 1716, 1418, 1221, 666 cmꢀ1; HRMS (ESI)
calcd for C26H23N2SO4 [M – N3]+ 459.1373, found 459.1388;
Rf 0.29 (Petroleum ether/EtOAc, 20/1).
Benzyl
1ꢀazidoꢀ7ꢀbromoꢀ9ꢀtosylꢀ1,3,4,9ꢀtetrahydroꢀ2Hꢀ
pyrido[3,4ꢀb]indoleꢀ2ꢀcarboxylate (2l). According to the genꢀ
eral procedure C. White solid (76.4 mg, 66%); M.p. = 52 – 54
°C. 1H NMR (400 MHz, CDCl3, rotamers seen) δ 8.16 (s, 1H),
7.70 (d, J = 6.8 Hz, 1H), 7.60 (d, J = 7.2 Hz, 1H), 7.40 –
7.21 (m, 7H), 7.13 (d, J = 12.0 Hz, 2H), 7.03 (d, J = 7.2
Hz, 1H), 5.32 – 5.07 (m, 2H), 4.33 (dd, J = 52.0, 9.2 Hz,
1H), 3.41 – 3.20 (m, 1H), 2.58 (dd, J = 30.4, 15.2 Hz, 2H),
67.8, 37.7 and 37.3, 22.1, 21.6 and 21.2; IR (neat) υmax
=
3116, 3032, 2104 (N3), 1716, 1699, 1547, 1501, 1418, 1362,
1167, 668 cmꢀ1; HRMS (ESI) calcd for C26H22ClN2SO4 [M –
N3]+ 493.0983, found 493.0989; Rf 0.30 (Petroleum
ether/EtOAc, 20/1).
2.24 (s, 3H).; δ
13C NMR (100 MHz, CDCl3, rotamers seen)
Benzyl
1ꢀazidoꢀ6ꢀbromoꢀ9ꢀtosylꢀ1,3,4,9ꢀtetrahydroꢀ2Hꢀ
154.35 and 153.2, 144.4, 136.0 and 135.9, 134.8 and 134.6,
134.0, 129.6 and 129.2, 129.0, 128.7, 127.7, 127.5, 127.3,
127.2, 126.2 and 126.1, 126.0 and 125.9, 125.7, 125.5,
119.4 and 119.3, 118.9 and 118.7, 118.6 and 118.5, 116.8
pyrido[3,4ꢀb]indoleꢀ2ꢀcarboxylate (2p). According to the genꢀ
eral procedure C. White solid (69.5 mg, 60%); M.p. = 87 – 88
°C. 1H NMR (400 MHz, CDCl3, rotamers seen) δ 8.00 – 7.89
ACS Paragon Plus Environment

Page 7 of 11
The Journal of Organic Chemistry
4ꢀazidoꢀ1,4ꢀdihydroꢀ2Hꢀbenzo[f]isochromene (4c). Accordꢀ
(m, 1H), 7.77 (d, J = 7.6 Hz, 1H), 7.67 (d, J = 7.6 Hz, 1H),
1
2
3
4
ing to the general procedure D. Colorless oil (66.9 mg,
7.51 (d, J = 9.6 Hz, 1H), 7.40 (m, 7H), 7.22 (s, 1H), 7.10
(d, J = 7.6 Hz, 1H), 5.30 (m, 2H), 4.42 (ddd, J = 53.2, 13.2,
5.2 Hz, 1H), 3.48 – 3.28 (m, 1H), 2.68 (m, 2H), 2.33 (s,
1
>99%); H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 7.6 Hz,
1H), 7.80 (d, J = 7.6 Hz, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.61 –
7.44 (m, 2H), 7.24 (d, J = 8.4 Hz, 1H), 6.15 (s, 1H), 4.40 –
4.13 (m, 2H), 3.37 – 2.91 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 132.4, 130.6, 129.3, 128.4, 128.0, 126.4, 126.0,
125.8, 123.1, 122.30, 87.1, 59.3, 23.7; IR (neat) υmax = 3154,
3012, 2097 (N3), 1558, 1507, 1418, 1101, 669 cmꢀ1; HRMS
(ESI) calcd for C13H11O [M – N3]+ 183.0804, found 183.0806;
Rf 0.19 (Petroleum ether/EtOAc, 60/1).
1ꢀazidoꢀ7ꢀmethoxyisochromane (4d). According to the genꢀ
eral procedure D. Colorless oil (40.0 mg, 65%); 1H NMR (400
MHz, CDCl3) δ 7.04 (d, J = 8.4 Hz, 1H), 6.83 (dd, J = 8.4, 2.4
Hz, 1H), 6.70 (d, J = 2.4 Hz, 1H), 6.02 (s, 1H), 4.12 (td, J =
11.2, 3.2 Hz, 1H), 4.06 – 3.98 (m, 1H), 3.78 (s, 3H), 2.93
(ddd, J = 16.6, 11.2, 5.6 Hz, 1H), 2.61 (d, J = 16.6 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 157.3, 132.1, 128.9, 124.8,
114.6, 110.0, 86.6, 59.8, 54.6, 26.1; IR (neat) υmax = 2936,
2907, 2101 (N3), 1558, 1506, 1238, 1088, 1036, 669 cmꢀ1;
HRMS (ESI) calcd for C10H11O2 [M – N3]+ 163.0754, found
163.0748; Rf 0.35 (Petroleum ether/EtOAc, 100/1).
3H).;
13C NMR (100 MHz, CDCl3, rotamers seen) δ 155.4 and
154.3, 145.4, 135.9, 135.7, 135.1, 131.6, 131.1, 130.0,
128.9, 128.7, 128.5, 128.4, 128.2, 126.8, 126.6, 122.2 and
122.1, 119.5, 119.1, 117.3, 116.3, 68.4 and 68.3, 67.2, 37.2
5
6
7
and 36.8, 21.6, 21.0 and 20.7; IR (neat) υmax = 3065, 2104
(N3), 1716, 1699, 1541, 1507, 1396, 1166, 668 cmꢀ1; HRMS
(ESI) calcd for C26H22BrN2SO4 [M – N3]+ 537.0478, found
537.0485; Rf 0.34 (Petroleum ether/EtOAc, 20/1).
Benzyl 1ꢀazidoꢀ6ꢀmethoxyꢀ9ꢀtosylꢀ1,3,4,9ꢀtetrahydroꢀ2Hꢀ
pyrido[3,4ꢀb]indoleꢀ2ꢀcarboxylate (2q). According to the genꢀ
eral procedure C. White solid (37.2 mg, 35%); M.p. = 144 –
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
145 °C. H NMR (400 MHz, CDCl3, rotamers seen) δ 8.06 –
7.92 (m, 1H), 7.76 (s, 1H), 7.70 – 7.59 (m, 1H), 7.51 – 7.31
(m, 5H), 7.30 – 7.14 (m, 2H), 7.06 (d, J = 7.6 Hz, 1H), 7.01 –
6.90 (m, 1H), 6.85 – 6.74 (m, 1H), 5.42 – 5.18 (m, 2H), 4.56 –
4.28 (m, 1H), 3.91 – 3.76 (m, 3H), 3.51 – 3.30 (m, 1H), 2.86 –
2.56 (m, 2H), 2.42 – 2.26 (m, 3H); 13C NMR (100 MHz,
CDCl3, rotamers seen) δ 155.8, 154.4 and 153.3, 143.9,
134.9 and 134.7, 134.1, 130.0 and 129.9, 129.7, 129.2,
128.8, 128.3 and 128.2, 127.6, 127.4, 127.3, 127.1, 125.6,
125.4, 119.6 and 119.2, 114.8, 113.8 and 113.6, 100.7,
67.2, 67.1 and 66.4, 54.6, 36.2 and 35.8, 20.5, 20.1 and
19.8; IR (neat) υmax = 2917, 2103 (N3), 1716, 1457, 1223,
1166, 664 cmꢀ1; HRMS (ESI) calcd for C27H25N2SO5 [M –
N3]+ 489.1479, found 489.1483; Rf 0.35 (Petroleum
ether/EtOAc, 7/1).
1ꢀazidoꢀ7ꢀmethylisochromane (4e). According to the genꢀ
eral procedure D. Colorless oil (39.7 mg, 70%); 1H NMR (400
MHz, CDCl3) δ 7.19 – 6.89 (m, 3H), 6.03 (s, 1H), 2.97 (ddd, J
= 16.8, 11.2, 5.6 Hz, 2H), 2.62 (dt, J = 16.8, 2.4 Hz, 2H), 2.32
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 135.7, 131.3, 130.0,
128.9, 128.0, 126.4, 87.0, 59.8, 26.8, 20.5; IR (neat) υmax
=
2976, 2927, 2101 (N3), 1558, 1507, 1224, 1090, 1062, 812,
669 cmꢀ1; HRMS (ESI) calcd for C10H11O [M – N3]+ 147.0804,
found 147.0804; Rf 0.45 (Petroleum ether).
1ꢀazidoꢀ5ꢀmethylisochromane (4f). According to the genꢀ
eral procedure D. Colorless oil (39.7 mg, 70%); 1H NMR (400
MHz, CDCl3) δ 7.14 (s, 2H), 7.03 (s, 1H), 6.04 (s, 1H), 4.39 –
3.98 (m, 2H), 2.90 – 2.72 (m, 1H), 2.58 (d, J = 16.6 Hz, 1H),
2.23 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 133.4, 129.3,
Synthesis of Compouds 4a-m. General Procedure D. An
ovenꢀdried Schlenk tube was charged with substrate 3 (0.3
mmol), T+BF4– (87.5 mg, 0.36 mmol) and 4A molecular
sieves (20 mg), and then dry acetonitrile (3.0 mL), trimethylsiꢀ
lazide (48 ꢁL, 0.36 mmol) was added by syringe. The reaction
mixture was stirred at room temperature for 4ꢀ12 h until the
consumption of the starting material, indicated by TLC. The
reaction mixture was concentrated in vacuum to give the crude
product, which was purified by common column chromatogꢀ
raphy (SiO2) to give the desired compounds.
129.0, 127.0, 123.4, 121.4, 85.0, 57.2, 22.5, 16.1; IR (neat)
υ
= 3013, 2974, 2098 (N3), 1558, 1497, 1222, 1102, 1058,
max
779 cmꢀ1; HRMS (ESI) calcd for C10H11O [M – N3]+ 147.0804,
found 147.0801; Rf 0.50 (Petroleum ether).
1ꢀazidoꢀ6ꢀbromoisochromane (4g). According to the genꢀ
eral procedure D. Colorless oil (44.0 mg, 58%); 1H NMR (400
MHz, CDCl3) δ 7.38 (dd, J = 8.0, 1.6 Hz, 1H), 7.32 (s, 1H),
7.08 (d, J = 8.0 Hz, 1H), 6.04 (s, 1H), 4.22 – 3.95 (m, 2H),
3.01 (ddd, J = 16.8, 11.2, 6.0 Hz, 1H), 2.67 (dt, J = 16.8, 2.8
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 136.2, 131.9, 131.4,
130.1, 128.6, 122.7, 87.1, 56.0, 27.7; IR (neat) υmax = 3101,
3032, 2099 (N3), 1558, 1507, 1093, 1057, 1026, 749, 669 cmꢀ1;
HRMS (ESI) calcd for C9H8BrO [M – N3]+ 210.9753, found
210.9748; Rf 0.50 (Petroleum ether).
1ꢀazidoisochromane (4a). According to the general proceꢀ
dure D. Colorless oil (34.1 mg, 65%); H NMR (400 MHz,
1
CDCl3) δ 7.31 – 7.21 (m, 2H), 7.21 – 7.16 (m, 1H), 7.16 –
7.11 (m, 1H), 6.07 (s, 1H), 4.15 (td, J = 11.2, 3.6 Hz, 1H),
4.05 (ddd, J = 11.2, 6.0, 3.6 Hz, 1H), 3.02 (ddd, J = 17.2, 11.2,
6.0 Hz, 1H), 2.77 – 2.59 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 134.2, 132.6, 129.3, 129.1, 127.1, 87.9, 60.7, 28.2;
IR (neat) υmax = 3032, 2099 (N3), 1636, 1558, 1507, 1089 cmꢀ
1; HRMS (ESI) calcd for C9H10NO [M –N2 + H]+ 148.0757,
found 148.0756; Rf 0.35 (Petroleum ether/EtOAc, 40/1).
1ꢀazidoꢀ3ꢀmethylisochromane (4h). According to the genꢀ
eral procedure D. Colorless oil (38.0 mg, 67%); 1H NMR (400
MHz, CDCl3) δ 7.53 – 6.96 (m, 4H), 6.14 (s, 1H), 4.26 (s, 1H),
2.70 (d, J = 4.4 Hz, 2H), 1.40 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 134.1, 132.0, 128.9, 128.8, 126.9, 126.7, 88.4, 66.0,
35.5, 21.4; IR (neat) υmax = 3101, 3032, 2098 (N3), 1558,
1507, 1077, 669 cmꢀ1; HRMS (ESI) calcd for C10H11O [M –
N3]+ 147.0804, found 147.0802; Rf 0.45 (Petroleum ether).
1ꢀazidoꢀ3ꢀethylisochromane (4i). According to the general
1ꢀazidoꢀ5ꢀ(chloromethyl)ꢀ7,8ꢀdimethoxyisochromane (4b).
According to the general procedure D. White solid (71.3 mg,
84%); M.p. = 70 – 71 °C. H NMR (400 MHz, CDCl3) δ 6.94
1
(s, 1H), 6.24 (s, 1H), 4.58 – 4.51 (m, 2H), 4.25 – 4.03 (m, 2H),
3.94 (s, 3H), 3.87 (s, 3H), 2.93 (ddd, J = 16.4, 12.0, 6.8 Hz,
1H), 2.69 (dd, J = 16.4, 3.6 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 150.7, 146.6, 130.7, 127.4, 125.8, 115.4, 85.4, 61.0,
59.3, 56.4, 44.1, 23.9; IR (neat) υmax = 3032, 2904, 2108 (N3),
1558, 1507, 1243, 1131, 1026, 669 cmꢀ1; HRMS (ESI) calcd
for C12H14ClO3 [M – N3]+ 241.0626, found 241.0625; Rf 0.25
(Petroleum ether/EtOAc, 60/1).
1
procedure D. Colorless oil (39.6 mg, 65%); H NMR (400
MHz, CDCl3) δ 7.38 – 7.04 (m, 4H), 6.17 (s, 1H), 4.02 (s, 1H),
2.70 (d, J = 6.0 Hz, 2H), 1.70 (s, 2H), 1.08 (s, 3H); 13C NMR
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 11
(100 MHz, CDCl3) δ 134.1, 132.2, 128.9, 128.7, 126.7, 126.6,
88.1, 71.1, 33.5, 28.5, 10.1; IR (neat) υmax = 2968, 2935,
2098 (N3), 1558, 1507, 1227, 1078, 747, 665 cmꢀ1; HRMS
(ESI) calcd for C11H13O [M – N3]+ 161.0961, found 161.0960;
Rf 0.32 (Petroleum ether/EtOAc, 100/1).
7.54 (m, 1H), 7.47 – 7.23 (m, 8H), 7.20 – 7.10 (m, 1H), 6.72
1
2
3
4
5
6
7
8
(d, J = 6.0 Hz, 2H), 5.35 – 5.10 (m, 2H), 4.41 – 4.19 (m, 1H),
4.04 – 3.83 (m, 1H), 3.75 (s, 3H), 2.98 (s, 2H); 13C NMR (100
MHz, CDCl3, rotamers seen) δ 160.2, 155.7 and 155.4, 148.3
and 148.1, 137.1 and 136.9, 136.6, 131.8, 130.8, 129.8, 129.6,
129.3, 129.0, 128.6 and 128.5, 128.3, 126.5, 123.8 and 123.5,
1ꢀazidoꢀ1,3ꢀdihydroisobenzofuran (4j). According to the
1
113.8, 71.7, 68.3, 55.8, 39.8 and 39.2, 29.3; IR (neat) υmax
=
general procedure D. Colorless oil (34.3 mg, 71%); H NMR
(400 MHz, CDCl3) δ 7.46 – 7.36 (m, 3H), 7.31 (d, J = 6.8 Hz,
1H), 6.34 (s, 1H), 5.33 (d, J = 12.4 Hz, 1H), 5.13 (d, J = 12.4
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 139.3, 136.4, 129.8,
128.4, 122.8, 121.4, 96.0, 74.0; IR (neat) υmax = 3011, 2925,
2100 (N3), 1558, 1507, 1226, 1033, 752 cmꢀ1; HRMS (ESI)
calcd for C8H7O [M – N3]+ 119.0491, found 119.0496; Rf 0.46
(Petroleum ether/EtOAc, 100/1).
3032, 1716, 1684, 1457, 1230, 694 cmꢀ1; HRMS (ESI) calcd
for C26H24N4O3 [M + Na]+ 463.1741, found 463.1737; Rf 0.22
(Petroleum ether/EtOAc, 10/1).
9
Benzyl
6,7ꢀdimethoxyꢀ1ꢀ(4ꢀphenylꢀ1Hꢀ1,2,3ꢀtriazolꢀ1ꢀyl)ꢀ
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3,4ꢀdihydroisoquinolineꢀ2(1H)ꢀcarboxylate (5b). According to
the general procedure E. White solid (63.5 mg, 45%); M.p. =
44 – 45 °C. 1H NMR (400 MHz, CDCl3, rotamers seen) δ 7.94
– 7.73 (m, 3H), 7.66 – 7.50 (m, 1H), 7.48 – 7.26 (m, 8H), 6.80
– 6.57 (m, 2H), 5.38 – 5.07 (m, 2H), 4.50 – 4.20 (m, 1H), 4.00
– 3.82 (m, 4H), 3.81 – 3.67 (m, 3H), 3.10 – 2.83 (m, 2H); 13C
NMR (100 MHz, CDCl3, rotamers seen) δ 155.7 and 155.3,
150.0, 148.5, 136.6, 132.2, 131.9, 130.8, 129.3, 129.1, 129.0,
128.6, 128.5, 128.4, 128.2 and 127.4, 126.6, 126.5, 123.3 and
122.9, 111.6, 110.7 and 110.5, 71.7, 68.4, 56.5, 56.4, 39.8 and
39.2, 28.7 and 28.6; IR (neat) υmax = 3032, 1733, 1716, 1558,
1253, 1201, 694 cmꢀ1; HRMS (ESI) calcd for C27H26N4O4 [M
+ Na]+ 493.1846, found 493.1838; Rf 0.25 (Petroleum
ether/EtOAc, 5/1).
1ꢀazidoꢀ1H,3Hꢀbenzo[d,e]isochromene (4k). According to
1
the general procedure D. Colorless oil (55.1 mg, 87%); H
NMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.4 Hz, 1H), 7.77 (d, J
= 8.4 Hz, 1H), 7.62 – 7.41 (m, 2H), 7.36 (d, J = 7.2 Hz, 1H),
7.25 (d, J = 7.2 Hz, 1H), 6.36 (s, 1H), 5.41 (d, J = 14.8 Hz,
1H), 5.04 (d, J = 14.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
133.2, 130.9, 129.4, 129.3, 127.3, 126.5, 126.2, 125.8, 123.1,
121.4, 88.9, 63.9; IR (neat) υmax = 3056, 2103 (N3), 1558,
1507, 1213, 1046, 817, 797 cmꢀ1; HRMS (ESI) calcd for
C12H9O [M – N3]+ 169.0648, found: 169.0644; Rf 0.46 (Petroꢀ
leum ether/EtOAc, 100/1).
Benzyl
6ꢀmethoxyꢀ1ꢀ(4ꢀphenylꢀ1Hꢀ1,2,3ꢀtriazolꢀ1ꢀyl)ꢀ9ꢀ
5ꢀazidoꢀ5,7ꢀdihydrodibenzo[c,e]oxepine (4l). According to
1
tosylꢀ1,3,4,9ꢀtetrahydroꢀ2Hꢀpyrido[3,4ꢀb]indoleꢀ2ꢀ
the general procedure D. Colorless oil (29.9 mg, 42%); H
carboxylate (5c). According to the general procedure E.
NMR (400 MHz, CDCl3) δ 7.64 – 7.49 (m, 4H), 7.49 – 7.39
(m, 4H), 5.99 (s, 1H), 4.50 (q, J = 11.6 Hz, 2H); 13C NMR
(100 MHz, CDCl3) δ 141.0, 139.8, 135.6, 134.3, 130.6, 130.1,
129.7, 129.4, 129.1, 128.9, 128.8, 127.9, 91.0, 68.2; IR (neat)
υmax = 3032, 2921, 2099 (N3), 1652, 1541, 1507, 1070, 1042,
755, 669 cmꢀ1; HRMS (ESI) m/z calcd for C14H11O [M – N3]+
195.0804, found: 195.0799; Rf 0.51 (Petroleum ether/EtOAc,
100/1).
1
White solid (155.7 mg, 82%); M.p. = 90 – 92 °C. H NMR
(400 MHz, CDCl3, rotamers seen) δ 8.20 (d, J = 10.0 Hz, 1H),
8.11 (s, 1H), 7.96 (d, J = 9.2 Hz, 1H), 7.83 (d, J = 7.2 Hz, 1H),
7.76 – 7.60 (m, 1H), 7.55 – 7.31 (m, 8H), 7.26 (d, J = 8.4 Hz,
1H), 7.15 (d, J = 8.4 Hz, 1H), 7.09 – 6.81 (m, 4H), 5.54 – 5.10
(m, 2H), 4.59 – 4.28 (m, 1H), 3.86 and 3.85 (s, 3H), 3.76 –
3.44 (m, 1H), 3.06 – 2.79 (m, 2H), 2.25 and 2.19 (s, 3H); 13C
NMR (100 MHz, CDCl3, rotamers seen) δ 156.9 and 156.8,
155.0, 147.1 and 147.0, 145.0 and 144.9, 135.7 and 135.6,
135.2 and 135.0, 131.5 and 131.4, 130.5 and 130.2, 129.7,
129.3, 129.2, 129.0, 128.8, 128.7, 128.5, 128.1, 126.1, 125.9,
125.8, 122.0, 121.6, 121.4, 120.8, 115.7, 115.3, 115.0, 101.8,
68.5 and 68.3, 63.7, 55.8, 37.3 and 36.8, 21.5 and 21.3, 21.0;
IR (neat) υmax = 3033, 2918, 1699, 1670, 1599, 1541, 1165,
669 cmꢀ1; HRMS (ESI) calcd for C27H25N2SO5 [M – C8H6N3]+
489.1479, found 489.1482; Rf 0.30 (Petroleum ether/EtOAc,
4/1).
9ꢀazidoꢀ9Hꢀxanthene (4m). According to the general proꢀ
1
cedure D. Colorless oil (61.6 mg, 92%); H NMR (400 MHz,
CDCl3) δ 7.46 (d, J = 7.6 Hz, 2H), 7.42 – 7.33 (m, 2H), 7.17 –
7.23 (m, 4H), 5.54 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
151.7, 130.3, 129.7, 123.9, 118.1, 117.2, 57.2; IR (neat) υmax
= 3116, 2087 (N3), 1418, 1259, 1212 cmꢀ1; HRMS (ESI) calcd
for C13H10NO [M – N2 + H]+ 196.0757, found 196.0759; Rf
0.40 (Petroleum ether).
Synthesis of Compouds 5a-d. General Procedure E. An
oven dried Schlenk tube was charged with substrate 1h, 1i, 1q
–
or 3a (0.3 mmol), T+BF4 (87.5 mg, 0.36 mmol) and 4A moꢀ
1ꢀ(isochromanꢀ1ꢀyl)ꢀ4ꢀphenylꢀ1Hꢀ1,2,3ꢀtriazole (5d). Acꢀ
cording to the general procedure E. White solid (54.0 mg,
lecular sieves (20 mg). The tube was evacuated and backfilled
with Ar (this process was repeated three times) and then
CH3CN (3 mL), trimethylsilazide (48 ꢁL, 0.36 mmol) was
added by syringe. The reaction mixture was stirred at room
temperature for 6ꢀ48 h until the consumption of the starting
material, indicated by TLC. Then a solution of phenylacetyꢀ
lene (50 ꢁL, 0.45 mmol), DIPEA (74 ꢁL, 0.45 mmol) and
copper iodide (5.7 mg, 0.03 mmol) in 2 mL CH3CN were addꢀ
ed by syringe. The reaction mixture was stirred at room temꢀ
perature for 3 h. And then the reaction mixture was concenꢀ
trated in vacuum to give the crude product, which was purified
by common column chromatography to give the desired comꢀ
pounds.
1
65%); M.p. = 100 – 101 °C. H NMR (400 MHz, CDCl3) δ
7.78 (d, J = 7.2 Hz, 2H), 7.64 (s, 1H), 7.46 – 7.15 (m, 6H),
7.09 (s, 1H), 6.99 (d, J = 7.2 Hz, 1H), 4.17 – 3.93 (m, 2H),
3.19 – 2.73 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 147.5,
134.6, 130.4, 130.0, 129.3, 129.2, 128.8, 128.2, 127.0, 125.9,
119.3, 83.8, 61.2, 27.6; IR (neat) υmax = 3032, 1716, 1699,
1419, 1115 cmꢀ1; HRMS (ESI) calcd for C17H15N3NaO [M +
Na]+ 300.1107, found 300.1101; Rf 0.20 (Petroleum
ether/EtOAc, 7/1).
Synthesis of Compouds 6. An oven dried Schlenk tube was
charged with substrate 1b (0.69 g, 2.0 mmol),
bis(triphenylphosphine)palladium(II) chloride (70.2 mg, 0.1
mmol), copper iodide (38.1 mg, 0.2 mmol) and Et3N (10 mL).
The tube was evacuated and backfilled with Ar (this process
6ꢀmethoxyꢀ1ꢀ(4ꢀphenylꢀ1Hꢀ1,2,3ꢀtriazolꢀ1ꢀyl)ꢀ3,4ꢀ
dihydroisoquinolineꢀ2(1H)ꢀcarboxylate (5a). According to the
o
1
was repeated three times) at ꢀ40 C and then phenylacetylene
general procedure E. Colorless oil (88.5 mg, 67%); H NMR
(0.33 mL, 3.0 mmol) was added by syringe. The reaction mixꢀ
(400 MHz, CDCl3, rotamers seen) δ 7.84 ꢀ7.74 (m, 3H), 7.64 –
ACS Paragon Plus Environment

Page 9 of 11
The Journal of Organic Chemistry
ture was stirred at 80 oC for 12 h until the consumption of 1b,
According to the general procedure F. White solid (308.8 mg,
84%); M.p. = 90 – 91 °C; H NMR (400 MHz, CDCl3, rotaꢀ
1
1
2
3
4
5
6
7
8
indicated by TLC. The reaction mixture was filtered through
celite pad and concentrated in vacuo to give the crude product,
which was purified by common column chromatography to
give desired compound 6 as yellow oil (0.54 g) in 74% yield.
1H NMR (400 MHz, CDCl3, rotamers seen) δ 7.76 – 7.50 (m,
1H), 7.47 – 7.23 (m, 10H), 7.18 – 6.99 (m, 2H), 5.20 (s, 2H),
4.84 (s, 2H), 3.85 – 3.55 (m, 2H), 2.95 – 2.68 (m, 2H); 13C
NMR (100 MHz, CDCl3, rotamers seen) δ 154.4 and 154.2,
135.6, 134.1 and 134.0, 133.7, 130.5, 130.4, 128.9 and 128.7,
127.9 and 127.8, 127.5, 127.4, 127.3, 126.8, 126.6, 125.2,
122.0, 120.0 and 119.7, 94.2, 85.3, 66.1, 44.2 and 44.0, 40.2
and 39.9, 28.1 and 27.8; HRMS (ESI) calcd for C25H22NO2 [M
mers seen) δ 8.10 ꢀ 7.81 (m, 4H), 7.79 – 7.60 (m, 6H), 7.50 (d,
J = 28.4 Hz, 7H), 7.41 – 7.28 (m, 5H), 7.25 – 6.92 (m, 6H),
6.87 – 6.61 (m, 1H), 5.41 – 4.71 (m, 2H), 4.67 – 3.76 (m, 2H),
3.08 – 2.47 (m, 2H), 2.36 – 2.10 (m, 3H). 13C NMR (100
MHz, CDCl3, rotamers seen) δ 154.9 and 154.2, 144.3, 143.7,
136.7, 136.6, 134.7, 134.6, 134.3 and 134.2, 133.4 and 133.3,
133.1, 133.0, 132.6, 132.5, 132.1, 132.0, 131.9 and 131.8,
131.2, 129.8, 129.3, 129.2, 128.6, 128.5, 128.4, 128.3, 128.2,
128.1, 127.7, 127.4, 126.7 and 126.6, 125.6, 123.7, 122.3,
122.1, 121.1, 119.7, 118.5, 115.1 and 114.6, 67.6 and 67.2,
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61.1 and 60.3, 37.4, 21.4, 21.2 and 21.0; IR (neat) υmax
=
+
H]+ 368.1645, found 368.1649; Rf 0.30 (Petroleum
3032, 2961, 1771, 1733, 1558, 1507, 1456, 1362, 1117, 1090,
746, 722, 669, 541 cmꢀ1; HRMS (ESI) m/z calcd for
C44H39N3O4PS [M + H]+ 736.2393, found 736.2400; Rf 0.40
(CH2Cl2/MeOH, 20/1).
ether/EtOAc, 20/1).
Synthesis of Compouds 7. An oven dried Schlenk tube was
–
charged with substrate 6 (0.3 mmol) and T+BF4 (87.5 mg,
0.36 mmol), and then CH3CN (3 mL), trimethylsilazide (48
ꢁL, 0.36 mmol) was added by syringe. The reaction mixture
was stirred at room temperature for 6 h until the consumption
of 6, indicated by TLC. The reaction mixture was concentrated
in vacuum to remove the solvent, and then iodine (381 mg, 1.5
mmol), NaHCO3 (25 mg, 0.3 mmol) and CH2Cl2 (3 mL) were
added. The reaction was stirred at room temperature for 24 h
under dark until the consumption of the starting material, indiꢀ
cated by TLC. The reaction mixture was concentrated in vacuꢀ
um to give the crude product, which was purified by common
column chromatography to give the desired compound 7 as
Synthesis of Compouds 9 and 11. General Procedure G.
An oven dried Schlenk tube was charged with substrate 2a or
2k (0.3 mmol) and PPh3 (236.1mg, 0.90 mmol), and then THF
(3 mL) was added by syringe. The reaction mixture was stirred
at room temperature for 12 h until the consumption of 2a or
2k, indicated by TLC. The reaction mixture was concentrated
in vacuum to remove the solvent, and then benzaldehyde (38
ꢁL, 0.36 mmol) and toluene (3 mL) were added. The reaction
was stirred at 80 oC for 24 h until the consumption of the startꢀ
ing material, indicated by TLC. The reaction mixture was conꢀ
centrated in vacuum to remove the solvent, and then NaBH4
(23 mg, 0.60 mmol) and MeOH (3 mL) were added. The reacꢀ
tion mixture was stirred at room temperature for 4 h. Finally
the reaction mixture was concentrated in vacuum to give the
crude product, which was purified by common column chroꢀ
matography to give the desired compounds.
1
yellow solid (69.8 mg) in 46% yield; M.p: 43 – 45 ºC. H
NMR (400 MHz, CDCl3) δ 8.06 (d, J = 8.4 Hz, 1H), 7.65 (t, J
= 8.0 Hz, 1H), 7.56 – 7.50 (m, 2H), 7.44 – 7.39 (m, 3H), 7.37
– 7.31 (m, 3H), 7.30 – 7.20 (m, 3H), 5.27 (s, 2H), 4.25 (t, J =
5.6 Hz, 2H), 3.25 (t, J = 5.6 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 154.7, 154.3, 145.0, 143.2, 139.5, 135.5, 134.8,
131.6, 130.8, 130.1, 128.4, 128.3, 128.1, 128.0, 127.7, 126.1,
118.9, 92.0, 68.4, 44.3, 29.6; HRMS (ESI) m/z calcd for
C25H20IN2O2 [M + H]+ 507.0564, found 507.0571; Rf 0.40
(Petroleum ether/EtOAc, 10/1).
Synthesis of Compouds 8 and 10. General Procedure F. A
50 mL oven dried Schlenk tube was charged with substrate 2a
or 2k (0.5 mmol, 1 equiv), PPh3 (0.52 g, 2 mmol, 4 equiv) and
THF (20 mL). The reaction mixture was stirred at room temꢀ
perature for 12 h until the consumption of the starting materiꢀ
al, indicated by TLC. The reaction mixture was concentrated
in vacuum to give the crude product, which was purified by
common column chromatography to give the desired comꢀ
pounds.
Benzyl
1ꢀ(benzylamino)ꢀ3,4ꢀdihydroisoquinolineꢀ2(1H)ꢀ
carboxylate (9). According to the general procedure G. Colorꢀ
less oil (50.2 mg, 45%); 1H NMR (400 MHz, CDCl3, rotamers
seen) δ 7.48 – 7.24 (m, 10H), 7.24 – 7.14 (m, 3H), 7.09 (s,
1H), 6.03 and 5.90 (s, 1H), 5.32 – 5.02 (m, 2H), 4.46 – 4.06
(m, 1H), 4.03 – 3.65 (m, 2H), 3.52 – 3.21 (m, 1H), 3.10 – 2.81
(m, 1H), 2.80 – 2.61 (m, 1H), 1.98 (s, 1H); 13C NMR (100
MHz, CDCl3, rotamers seen) δ 154.6, 139.6 and 139.2, 135.8
and 135.4, 134.7 and 134.5, 134.1 and 133.9, 127.8, 127.5,
127.3, 127.2, 127.1, 126.9, 126.8, 126.5, 125.8, 125.2, 66.5
and 66.3, 66.0, 48.6 and 48.1, 36.4 and 35.7, 27.8 and 27.5; IR
(neat) υmax = 3030, 2918, 1684, 1636, 1541, 1456, 1245,
1118, 774, 696 cmꢀ1; HRMS (ESI) m/z calcd for C24H25N2O2
[M + H]+ 373.1911, found 373.1906; Rf 0.40 (Petroleum
ether/EtOAc, 10/1).
Benzyl
1ꢀ((triphenylꢀl5ꢀphosphaneylidene)amino)ꢀ3,4ꢀ
dihydroisoquinolineꢀ2(1H)ꢀcarboxylate (8). According to the
general procedure F. White solid (233.0 mg, 86%); M.p. = 50
Benzyl
1ꢀ(benzylamino)ꢀ9ꢀ(phenylsulfonyl)ꢀ1,3,4,9ꢀ
tetrahydroꢀ2Hꢀpyrido[3,4ꢀb]indoleꢀ2ꢀcarboxylate (11). Acꢀ
cording to the general procedure G. Colorless oil (105.0 mg,
1
– 51 °C. H NMR (400 MHz, CDCl3, rotamers seen) δ 7.98 –
1
7.23 (m, 19H), 7.15 – 6.45 (m, 5H), 6.40 – 5.80 (m, 1H), 4.35
– 4.55 (m, 2H), 4.46 – 3.82 (m, 2H), 3.07 – 2.56 (m, 2H); 13C
NMR (100 MHz, CDCl3, rotamers seen) δ 154.8, 136.9, 136.5,
134.8, 133.9, 133.4, 133.3, 133.0, 132.8, 132.7, 132.2, 132.1,
131.5, 128.7, 128.5, 128.4, 128.2 and 128.1, 128.0 and 127.9,
127.6, 126.5 and 126.3, 126.0 and 125.7, 66.9, 66.6 and 65.3,
37.7 and 37.1, 29.1 and 28.8; IR (neat) υmax = 3032, 1653,
1521, 1419, 1115, 1053 cmꢀ1; HRMS (ESI) m/z calcd for
C35H32N2O2P [M + H]+ 543.2196, found 543.2202; Rf 0.45
(CH2Cl2/MeOH, 20/1).
62%); H NMR (400 MHz, CDCl3, rotamers seen) δ 8.14 (dd,
J = 8.4, 4.4 Hz, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 8.0
Hz, 1H), 7.47 – 7.27 (m, 11H), 7.26 – 7.19 (m, 2H), 7.14 (d, J
= 8.0 Hz, 1H), 6.82 (d, J = 8.0 Hz, 1H), 6.68 and 6.57 (s, 1H),
5.26 – 5.10 (m, 2H), 4.45 – 4.02 (m, 2H), 3.93 (t, J = 11.6 Hz,
1H), 3.74 – 3.51 (m, 1H), 2.92 – 2.68 (m, 1H), 2.61 (td, J =
16.6, 4.4 Hz, 1H), 2.42 – 2.06 (m, 4H); 13C NMR (100 MHz,
CDCl3, rotamers seen) δ 154.5 and 154.0, 143.8 and 143.7,
139.2, 138.8, 135.5 and 135.4, 135.3 and 135.2, 134.0 and
133.8, 132.6 and 132.2, 128.7, 128.5, 128.2 and 128.1,
127.6, 127.4, 127.2, 127.2, 126.9, 126.7, 125.9 and 125.9,
125.7, 125.6, 124.3 and 124.2, 122.7 and 122.6, 118.5 and
Benzyl 9ꢀtosylꢀ1ꢀ((triphenylꢀl5ꢀphosphaneylidene)amino)ꢀ
1,3,4,9ꢀtetrahydroꢀ2Hꢀpyrido[3,4ꢀb]indoleꢀ2ꢀcarboxylate (10).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 11
Wang, Y.; Antilla, J. C. J. Am. Chem. Soc. 2005, 127, 15696;
118.2, 117.8 and 117.7, 113.9, 113.2, 66.4 and 66.1, 64.8
and 64.3, 50.5 and 50.3, 34.4 and 34.0, 20.4, 19.9; IR (neat)
υmax = 3032, 2919, 1684, 1541, 1456, 1419, 1220, 1090 cmꢀ1;
HRMS (ESI) m/z calcd for C33H32N3O4S [M + H]+ 566.2108,
found 566.2100; Rf 0.48 (Petroleum ether/EtOAc, 10/1).
1
2
3
4
5
6
7
8
(c) Connon, S. J. Angew. Chem., Int. Ed. 2006, 45, 3909; (d)
Liang, Y.; Rowland, E. B.; Rowland, G. B.; Perman, J. A.;
Antilla, J. C. Chem. Commun. 2007, 4477; (e) Neel, A. J.;
Hehn, J. P.; Tripet, P. F.; Toste, F. D. J. Am. Chem. Soc. 2013,
135, 14044; (f) Orlandi, M.; Toste, F. D.; Sigman, M. S. Anꢀ
gew. Chem., Int. Ed. 2017, 56, 14080.
(5) Li, G.; Fronczek, F. R.; Antilla, J. C. J. Am. Chem. Soc.
2008, 130, 12216.
(6) (a) Yang, T.; Wang, W.; Wei, D.; Zhang, T.; Han, B.;
Yu, W. Org. Chem. Front. 2017, 4, 421ꢀ426. (b) Pedersen, C.
M.; Marinescu, L. G.; Bols, M. Org. Biomol. Chem. 2005, 3,
816.
(7) (a) Kobayashi, J.; Cheng, J. F.; Ohta, T.; Nozoe, S.;
Ohizumi, Y.; Sasaki, T. J. Org. Chem. 1990, 55, 3666ꢀ3670;
(b) Kato, N.; Comer, E.; SakataꢀKato, T.; Sharma, A.; Sharma,
M.; Maetani, M.; Bastien, J.; Brancucci, N. M.; Bittker, J. A.;
Corey, V.; Clarke, D.; Derbyshire, E. R.; Dornan, G. L.;
Duffy, S.; Eckley, S.; Itoe, M. A.; Koolen, K. M. J.; Lewis, T.
A.; Lui, P. S.; Lukens, A. K.; Lund, E.; March, S.; Meibalan,
E.; Meier, B. C.; McPhail, J. A.; Mitasev, B.; Moss, E. L.;
Sayes, M.; Van Gessel, Y.; Wawer, M. J.; Yoshinaga, T.;
Zeeman, A.ꢀM.; Avery, V. M.; Bhatia, S. N.; Burke, J. E.;
Catteruccia, F.; Clardy, J. C.; Clemons, P. A.; Dechering, K.
J.; Duvall, J. R.; Foley, M. A.; Gusovsky, F.; Kocken, C. H.
M.; Marti, M.; Morningstar, M. L.; Munoz, B.; Neafsey, D. E.;
Sharma, A.; Winzeler, E. A.; Wirth, D. F.; Scherer, C. A.;
Schreiber, S. L. Nature 2016, 538, 344; (c) Tokuda, R.; Okaꢀ
moto, Y.; Koyama, T.; Kogure, N.; Kitajima, M.; Takayama,
H. Org. Lett. 2016, 18, 3490.
(8) CH3ꢀprotected tetrahydroꢀβꢀcarbolines were also used,
but the reaction became mess when we detected by TLC.
(9) (a) Xia, Q.; Wang, Q.; Yan, C.; Dong, J.; Song, H.; Li,
L.; Liu, Y.; Wang, Q.; Liu, X.; Song, H. Chem.–Eur. J. 2017,
23, 10871. (b) SchweitzerꢀChaput, B.; Klussmann, M. Eur. J.
Org. Chem. 2013, 666.
(10) (a) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew.
Chem., Int. Ed. 2001, 40, 2004ꢀ2021; (b) Sletten, E. M.;
Bertozzi, C. R. Acc. Chem. Res. 2011, 44, 666.
(11) (a) Köhn, M.; Breinbauer, R. Angew. Chem., Int. Ed.
2004, 43, 3106; (b) van Berkel, S. S.; van Eldijk, M. B.; van
Hest, J. C. M. Angew. Chem., Int. Ed. 2011, 50, 8806.
(12) (a) Richter, H.; Mancheno, O. G. Eur. J. Org. Chem.
2010, 4460. (b) Yan, C. C.; Liu, Y. X.; Wang, Q. M. RSC Adv.
2014, 4, 60075. (c) Yan, C. C.; Liu, Y. X.; Wang, Q. M. Org.
Lett. 2015, 17, 5714. (d) Richter, H.; Frohlich, R.; Daniliuc,
C.ꢀG.; Mancheno, O. G. Angew. Chem., Int. Ed. 2012, 51,
8656; (e) Srivastava, A. K.; Koh, M.; Park, S. B. Chem. Eur. J.
2011, 17, 4095; (f) Hamlin, T. A.; Kelly, C. B.; Ovian, J. M.;
Wiles, R. J.; Tilley, L. J.; Leadbeater, N. E. J. Org. Chem.
2015, 80, 8150.
(13) (a) Murahashi, S.ꢀI.; Komiya, N.; Terai, H. Angew.
Chem., Int. Ed. 2005, 44, 6931. (b) Boess, E.; Sureshkumar,
D.; Sud, A.; Wirtz, C.; Farès, C.; Klussmann, M. J. Am. Chem.
Soc. 2011, 133, 8106. (c) Jung, H. H.; Floreancig, P. E. Tetraꢀ
hedron 2009, 65, 10830. (d) Chen, Q.; Zhou, J.; Wang, Y.;
Wang, C.; Liu, X.; Xu, Z.; Lin, L.; Wang, R. Org. Lett. 2015,
17, 4212.
ASSOCIATED CONTENT
Supporting Information
9
Experimental procedures, characterization data of all compounds,
1
copies of H NMR and 13C NMR of all compounds (PDF). The
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Supporting Information is available free of charge on the ACS
Publications website.
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: wangqm@nankai.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We are grateful to the National Natural Science Foundation of
China (21732002, 21672117, 21602117) and the Tianjin Natural
Science Foundation (16JCZDJC32400) for generous financial
support for our programs.
REFERENCES
(1) For selected examples of bioactive molecules and funcꢀ
tional materials that consist of aminal structural units:(a)
Huang, G.; Kling, B.; Darras, F. H.; Heilmann, J.; Decker, M.
Eur. J. Med. Chem. 2014, 81, 15; (b) Darras, F. H.; Kling, B.;
Heilmann, J.; Decker, M. ACS. Med. Chem. Lett. 2012, 3, 914;
(c) Liang, X.; Zhang, T.ꢀY.; Zeng, X.ꢀY.; Zheng, Y.; Wei, K.;
Yang, Y.ꢀR. J. Am. Chem. Soc. 2017, 139, 3364; (d) Sohn, J.ꢀ
H.; Waizumi, N.; Zhong, H. M.; Rawal, V. H. J. Am. Chem.
Soc. 2005, 127, 7290; (e) Li, Y.; Zhang, G.; Yang, G.; Guo,
Y.; Di, C. a.; Chen, X.; Liu, Z.; Liu, H.; Xu, Z.; Xu, W.; Fu,
H.; Zhang, D. J. Org. Chem. 2013, 78, 2926.
(2) (a) Polshettiwar, V.; Varma, R. S. Tetrahedron. Lett.
2008, 49, 7165; (b) Zhang, C.; De, C. K.; Mal, R.; Seidel, D.
J. Am. Chem. Soc. 2008, 130, 416; (c) Zhang, C.; Murarka, S.;
Seidel, D. J. Org. Chem. 2009, 74, 419; (d) He, Y.; Cheng, C.;
Chen, B.; Duan, K.; Zhuang, Y.; Yuan, B.; Zhang, M.; Zhou,
Y.; Zhou, Z.; Su, Y.ꢀJ.; Cao, R.; Qiu, L. Org. Lett. 2014, 16,
6366; (e) Li, H.; Belyk, K. M.; Yin, J.; Chen, Q.; Hyde, A.; Ji,
Y.; Oliver, S.; Tudge, M. T.; Campeau, L.ꢀC.; Campos, K. R.
J. Am. Chem. Soc. 2015, 137, 13728; (f) Horibe, T.; Ohmura,
S.; Ishihara, K. Org. Lett. 2017, 19, 5525; (g) Zhu, Z.; Lv, X.;
Anesini, J. E.; Seidel, D. Org. Lett. 2017, 19, 6424.
(3) (a) Goodman, M.; Chorev, M. Acc. Chem. Res. 1979,
12, 1; (b) Fuller, W. D.; Goodman, M.; Verlander, M. S. J.
Am. Chem. Soc. 1985, 107, 5821; (c) Chorev, M.; Goodman,
M. Acc. Chem. Res. 1993, 26, 266.
(4) For selected functionalization of CꢀH bonds to prepare
aminals： (a) Manzo, A. M.; Perboni, A. D.; Broggini, G.;
Rigamonti, M. Tetrahedron. Lett. 2009, 50, 4696; (b) Rowꢀ
land, G. B.; Zhang, H.; Rowland, E. B.; Chennamadhavuni, S.;
(14) For selected recent examples of αꢀC–H functionalizaꢀ
tion reactions of Nꢀacyl THIQs, see: (a) Ghobrial, M.; Harꢀ
hammer, K.; Mihovilovic, M. D.; Schnurch, M. Chem. Comꢀ
mun. 2010, 46, 8836; (b) Ghobrial, M.; Schnurch, M.; Miꢀ
hovilovic, M. D. J. Org. Chem. 2011, 76, 8781; (c) Xie, Z. Y.;
ACS Paragon Plus Environment

Page 11 of 11
The Journal of Organic Chemistry
Liu, L.; Chen, W. F.; Zheng, H. B.; Xu, Q. Q.; Yuan, H. Q.;
Lou, H. X. Angew. Chem. Int. Ed. 2014, 53, 3904; (d) Sun, S.
1
T.; Li, C. K.; Floreancig, P. E.; Lou, H. X.; Liu, L. Org. Lett.
2015, 17, 1684; (e) Punirun, T.; Soorukram, D.; Kuhakarn, C.;
Reutrakul, V.; Pohmakotr, M. J. Org. Chem. 2018, 83, 765; (f)
Huo, C.; Wu, M.; Chen, F.; Jia, X.; Yuan, Y.; Xie, H. Chem
Commun. 2015, 51, 4708; (g) Huo, C.; Wu, M.; Jia, X.; Xie,
H.; Yuan, Y.; Tang, J. J. Org. Chem. 2014, 79, 9860; (h) Huo,
C.; Yuan, Y.; Wu, M.; Jia, X.; Wang, X.; Chen, F.; Tang, J.
Angew Chem Int Ed. 2014, 53, 13544ꢀ7.
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment