Photocatalyzed Csp3-Csp3cross-dehydrogenative coupling of: N -Boc-tetrahydroisoquinolines with α,β-unsaturated ketones

Article abstract of DOI:10.1039/d1ob00527h

A novel photocatalyzed cross-dehydrogenative coupling reaction of N-Boc-tetrahydroisoquinolines with α,β-unsaturated ketones has been developed. This research provides an easy access to a variety of C1-substituted tetrahydroisoquinolines, which can be further transformed into benzo[a]-quinolizine-2-ones, the skeletons of natural products with a wide range of biological activities. The load of the photocatalyst is low and the oxidant is inexpensive and less toxic.

Full text of DOI:10.1039/d1ob00527h

Organic &
Biomolecular Chemistry
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Photocatalyzed Csp3–Csp3 cross-dehydrogenative
coupling of N-Boc-tetrahydroisoquinolines with
α,β-unsaturated ketones†
Cite this: Org. Biomol. Chem., 2021,
19, 4752
Na-Ri-Mei Ao, Xue-Qing Zhu, Chun-Xin Zhao, Ya-Ru Gao * and
Yong-Qiang Wang
*
A novel photocatalyzed cross-dehydrogenative coupling reaction of N-Boc-tetrahydroisoquinolines with
α,β-unsaturated ketones has been developed. This research provides an easy access to a variety of C1-
substituted tetrahydroisoquinolines, which can be further transformed into benzo[a]-quinolizine-2-ones,
the skeletons of natural products with a wide range of biological activities. The load of the photocatalyst
is low and the oxidant is inexpensive and less toxic.
Received 18th March 2021,
Accepted 1st May 2021
DOI: 10.1039/d1ob00527h
rsc.li/obc
Furthermore, ketones as coupling partners were always trans-
formed into more reactive enolates and their derivatives such
Introduction
α,β-Unsaturated ketones are key building blocks in modern as silyl enol ethers or enamine, because of the relatively low
organic synthesis due to their involvement in various funda- reactivity of ketones as electrophiles.7d,f,n The report on unsa-
mental transformations.1 So far the reactive sites of turated ketones was scarce. Thus, realizing this type of reaction
α,β-unsaturated ketones are mainly located at the carbonyl under mild conditions is still a challenge. Inspired by the
group (e.g., 1,2-addition)2 and the CvC double bond side, importance of these biological molecules, and based on our
such as the α-position (e.g., Baylis–Hillman reaction)3 and the long-standing interest in C–H direct functionalization, we
β-position (e.g., Michael addition)4 (Fig. 1). In contrast, the would like to develop a visible-light-mediated photocatalytic
direct reaction on the other side of the carbonyl group was CDC reaction of N-Boc-THIQs with α,β-unsaturated ketones.
much less reported. Herein, we report a new reaction of
α,β-unsaturated ketones, a direct functionalization of α′-C
(sp3)–H on the other side of the carbonyl group;
α,β-unsaturated ketones need not be pre-functionalized.
Results and discussion
To begin our study, we examined the CDC reaction of N-Boc-
Due to the abundance of biologically relevant molecules
containing the tetrahydroisoquinoline (THIQ) motif (Fig. 2),5
the cross-dehydrogenative coupling (CDC) reaction of THIQs
has attracted intense attention from synthetic chemists.6 The
visible-light-mediated photocatalytic CDC reaction of N-aryl-
THIQ has obtained extensive attention as a capable and envir-
onmentally benign method in the past decade.7 The aryl group
linked to the nitrogen weakens the target C–H bond, but aryl
is difficult to remove for the subsequent reaction, which may
limit the downstream utility of these products. Compared to
the N-aryl group, the N-carbamyl group decreases the reactivity
tetrahydroisoquinoline 1a and α,β-unsaturated ketone 2a in
the presence of 5 mol% Ru(bpy)3Cl2·6H2O in CH3CN under 10
W blue LED irradiation with molecular oxygen as the oxidant
(Table 1, entry 1). Unfortunately, no desired product was
obtained; instead 1a was oxidized to the corresponding amide
(N-Boc-3,4-dihydroisoquinolin-1(2H)-one). Then, various other
oxidants were examined, and in order to avoid the influence of
oxygen, the reaction was performed under an Ar atmosphere
(entries 2–6). When tert-butyl hydroperoxide (TBHP) and 2,3-
of THIQ; only
a
few examples have been reported.6f–h
Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry
of Education, National Demonstration Center for Experimental Chemistry Education,
College of Chemistry & Materials Science, Northwest University, Xi’an 710069,
People’s Republic of China. E-mail: gyaru@nwu.edu.cn, wangyq@nwu.edu.cn
†Electronic supplementary information (ESI) available: Experimental details,
characterization data. See DOI: 10.1039/d1ob00527h
Fig. 1 The reactions on α,β-unsaturated ketone.
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catalyst or an oxidant, and the reaction hardly proceeded in
the dark (entries 14–16). The control experiments showed that
the Ru(bpy)3Cl2·6H2O photoredox catalyst, the oxidant
(NH4)2S2O8 and blue light were essential for the reaction.
With the established optimal reaction conditions in hand,
we set out to explore the scope of this transformation
(Scheme 1). Firstly, the CDC reaction was applied to various
α,β-unsaturated ketones with tert-butyl 3,4-dihydroisoquino-
line-2(1H)-carboxylate (1a). The effect of electronic and struc-
tural variation on the β-position of aromatic rings was initially
examined. The alkyl groups (–Me, –Et, –iPr, –iBu, –tBu) on the
para-site of aromatic rings of α,β-unsaturated ketones could
afford the desired products in moderate to good yields (3ab–
3af). Halogens (–F, –Cl, –Br, –I) on the para-aromatic rings still
afforded the corresponding products in good yields (3ag–3aj).
Both electron-donating group (–OMe) and strong electron-with-
drawing group (–NO2) on the para-aromatic rings didn’t influ-
ence the reaction outcome, and they afforded the desired pro-
ducts in moderate yields (3ak, 3al). However, α,β-unsaturated
ketones bearing electron-withdrawing groups such as methoxy-
carbonyl (–COOMe) or cyano (–CN) at the para-positions could
not afford the desired product, but gave complex by-products.
Electron-withdrawing groups such as methoxycarbonyl
(–COOMe) or halogen (–F, –Cl, –Br) groups on the ortho-aromatic
rings were still suitable for the reaction conditions to afford
the corresponding products in moderate yields (3am–3ap). An
Fig. 2 Natural products containing THIQs.
Table 1 Optimization and control studiesa
Entry
Photocat.
Oxidant
Solvent
Yieldb [%]
1c
2
[Ru]
[Ru]
O2
TBHP
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
0
0
0
3
4
[Ru]
[Ru]
DDQ
Na2S2O8
15
19
26
63
13
42
38
15
81
55
0
5
[Ru]
[Ru]
[Ru]
[Ir]
Eosin Y
Riboflavin
Mes-Acr+ClO4
[Ru]
[Ru]
[Ru]
K2S2O8
6
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
None
7d
8
9
10
11
12e
13e, f
14e,g
15h
16e,i
−
None
[Ru]
(NH4)2S2O8
(NH4)2S2O8
Trace
0
a Unless noted otherwise, reactions were conducted with 1a
(0.2 mmol), 2a (0.1 mmol), photocatalyst (0.005 mmol, 5 mol%),
oxidant (0.2 mmol), solvent (1.0 mL), 10 W blue LEDs at room temp-
erature under an Ar atmosphere for 12 h. b Isolated yield. c Under an
oxygen atmosphere. d The yield of other solvents: EtOH (32%), DMF
(10%), THF (NR), Et2O (5%), 1,2-propanediol (12%), H2O (NR).
e Photocatalyst (0.001 mmol, 1 mol%). f White light. g No oxidant. h No
photocatalyst. i In the dark. [Ru] = Ru(bpy)3Cl2·6H2O. [Ir] = Ir(dtbbpy)
(ppy)2PF6. Eosin Y = 2,4,5,7-tetrabromofluorescein disodium salt.
dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) were added, no
desired coupling product was obtained (entries 2 and 3). Due
to the high potential of the peroxydisulfate ion, peroxydisulfate
salts were added. To our delight, the desired product 3aa was
obtained, albeit in a low yield. Among peroxydisulfate salts,
(NH4)2S2O8 showed higher efficiency than Na2S2O8 and K2S2O8
(entries 4–6). Other solvents were then tested, methanol was
more suitable than acetonitrile and other solvents with a good
yield and reaction rate (entry 7). Then we tested the reactivities
of other photocatalysts including the Ir(dtbbpy)(ppy)2PF6
complex, eosin Y, riboflavin, and Mes-Acr+ClO4− (entries 8–11).
They showed lower reactivities than Ru(bpy)3Cl2·6H2O. To our
delight, when the photocatalyst loading was reduced to
1 mol%, the amount of the by-product was decreased and 3aa
was obtained with a good yield (entry 12). Changing blue LEDs
to white LEDs decreased the rate and yield (entry 13). Little or
Scheme 1 Substrate scope. Reaction conditions: 1a (0.2 mmol),
(0.1 mmol), Ru(bpy)3Cl2·6H2O (1 mol%), (NH4)2S2O8 (0.2 mmol), CH3OH
(1.0 mL), 10 W blue LEDs at room temperature under an Ar atmosphere
2
no conversion was observed without the addition of a photo- for 12 h. Isolated yield.
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alkyl group (–Me) or halogens (–F, –Cl) on the meta-aromatic
rings could give the products with good yields (3aq–3as). Both
1,2-disubstituted and 1,3-disubstituted groups on aromatic rings
reacted well with moderate yields (3at, 3au). When the substitu-
ent R was an alkyl group (2av, 2aw), the desired products were
obtained with 45% and 54% yields, respectively (3av, 3aw).
Unfortunately, for aromatic heterocycles, such as 4-(4-pyridinyl)-
3-buten-2-one and 4-(2-thienyl)-3-buten-2-one, no reaction
occurred (3ax, 3ay).
Scheme 3 The transformation to benzo[a]quinolizidine.
Then the scope of N-Boc-THIQs was also examined under
the optimal reaction conditions (Scheme 2). The substitution
on the benzene ring of N-Boc-THIQs with electron-donating
groups (6,7-(MeO)2) or an electron-withdrawing group (5-Br)
could provide the desired products in good yields (3ba, 3ca).
Only a low yield was obtained for the substrate bearing an elec-
tron-withdrawing group (–NO2) on the aryl ring of THIQ (3da).
Pleasingly, dihydro-β-carboline was also suitable for the
optimal reaction conditions to give the desired product with
78% yield (3ea). When we checked the substrate scope of tetra-
hydroisoquinolines, other N-protecting groups were examined.
However, under the reaction conditions, N-phenyl-tetrahydroi-
soquinoline was decomposed and no desired product was
obtained. When the N-protecting groups were tosyl or o-nosyl,
no reaction occurred.
Next, to test the applicability for the synthesis of benzo[a]
quinolizine analogs, the protecting group (–Boc) of 3aa was
readily removed by TFA, and then intramolecular Michael
addition in NH3·H2O/methanol afforded benzo[a]quinolizi-
dine-2-ones (4a : 4b = 3 : 1) (Scheme 3). The relative stereoselec-
tivities were confirmed by comparing with the literature.5d
Based on the reaction outcomes and the previous reports,8
we proposed a catalytic cycle for the CDC reaction (Scheme 4).
Under blue LED irradiation, Ru2+ was transformed to Ru2+*.
Then the peroxydisulfate salt (NH4)2S2O8 was reduced by Ru2+*
to produce the sulfate radical anion (SO4·−), while Ru2+* was
Scheme 4 Proposed reaction mechanism.
oxidized to Ru3+. The hydrogen atom of substrate 1 was
abstracted by the sulfate radical anion to produce α-carbamyl
radical 5. Direct oxidation of 5 by Ru3+ can lead to the
iminium ion 6, which was susceptible to attack by
α,β-unsaturated ketones to afford the desired coupling
products.
Conclusions
In conclusion, we have developed a photocatalyzed cross-dehy-
drogenative coupling reaction of N-Boc-tetrahydroisoquino-
lines with α,β-unsaturated ketones, which provides access to
Mannich type products. This research work provides an easy
access to a variety of C1-substituted tetrahydroisoquinolines
that can be further transformed into benzo[a]-quinolizine-2-
ones. The application of this reaction to the synthesis of alka-
loid natural products is the subject of ongoing research.
Experimental section
General information
All dry reactions were carried out under argon. Unless other-
wise noted, all commercial reagents and solvents were used as
received without further purification. The progress of the reac-
tions was monitored by TLC with silica gel plates (GF254), and
the visualization was carried out under UV light. Melting
points (m.p.) were measured on electrothermal digital melting
1
point apparatus and were uncorrected. The H and 13C NMR
spectroscopic data were recorded with a Varian Unity Inova-
400 spectrometer or a Bruker Ascend 400 spectrometer (1H
and 13C NMR at 400 and 100 MHz, respectively). The spectra
were referenced internally to the residual proton resonance in
CDCl3 (δ 7.26 ppm), or with tetramethylsilane (TMS, δ
Scheme 2 Substrate scope. Reaction conditions: 1 (0.2 mmol), 2a
(0.1 mmol), Ru(bpy)3Cl2·6H2O (1 mol%), (NH4)2S2O8 (0.2 mmol), CH3OH
(1.0 mL), 10 W blue LEDs at room temperature under an Ar atmosphere
for 12 h. Isolated yield.
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0.00 ppm) as the internal standard. Chemical shifts (δ) were 137.0, 134.4, 134.3, 132.1, 131.8, 129.1, 128.7, 128.54, 128.49,
reported as parts per million (ppm) in the δ scale downfield 127.2, 127.0, 126.9, 126.4, 125.6, 125.4, 80.3, 79.9, 52.0, 51.6,
from TMS. Multiplicities are reported as follows: s = singlet, d 48.6, 48.3, 39.4, 37.6, 28.8, 28.4, 15.3. IR (thin film): 2966,
= doublet, t = triplet, m = multiplet, br. s = broad singlet. 1685, 1602, 1416, 1364, 1233, 1160, 1119, 1094, 961, 823,
Infrared (IR) data were recorded as films on potassium 753 cm−1. HRMS (ESI) m/z calculated for C26H32NO3 [M + H]+:
bromide plates on a Bruker Invenio-R FT-IR spectrometer. 406.2377; found: 406.2378.
Absorbance frequencies are reported in reciprocal centimeters
tert-Butyl(E)-1-(4-(4-isopropylphenyl)-2-oxobut-3-en-1-yl)-3,4-
(cm−1). High resolution mass spectra were acquired on a dihydroisoquinoline-2(1H)-carboxylate (3ad). Yellow gum
1
Bruker Daltonics MicroTof-QII mass spectrometer.
(31.4 mg, 75%). H NMR (400 MHz, CDCl3) δ 7.60–7.46 (br m,
3H), 7.25–7.15 (m, 6H), 6.82–6.71 (m, 1H), 5.71 (d, J = 31.3 Hz,
1H), 4.25–3.88 (br m, 1H), 3.50–3.28 (br m, 1H), 3.17 (dd, J =
General procedure
To a 10 mL round-bottom flask were added N-Boc-THIQs 1 14.5, 7.1 Hz, 1H), 2.87–2.02 (br m, 4H), 1.42 (s, 9H), 1.25 (d, J =
(0.2 mmol), an unsaturated ketone
(0.1 mmol), Ru 6.9 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ 197.7, 197.4, 154.6,
2
(bpy)3Cl2·6H2O (0.001 mmol), and (NH4)2S2O8 (0.2 mmol). The 154.3, 152.1, 151.8, 143.2, 143.1, 137.1, 134.4, 132.3, 132.0,
flask was degassed for 1 min and then filled with argon gas. 129.1, 128.7, 128.5, 127.2, 127.0, 126.9, 126.4, 125.7, 125.5,
Then MeOH (1.0 mL) was added. Finally, the mixture was 80.4, 79.9, 52.0, 51.6, 48.6, 48.4, 39.4, 37.7, 34.1, 28.4, 23.8. IR
stirred at a distance of 5 cm from 10 W blue LED strips for (thin film): 2961, 1689, 1604, 1417, 1365, 1234, 1164, 1120,
irradiation at room temperature under an Ar atmosphere for 1095, 961, 823, 753 cm−1. HRMS (ESI) m/z calculated for
12 h. The reaction was nearly completed, as monitored by TLC C27H33NO3Na [M + Na]+: 442.2353; found: 442.2353.
analysis. After completion, the reaction mixture was concen-
tert-Butyl(E)-1-(4-(4-isobutylphenyl)-2-oxobut-3-en-1-yl)-3,4-
trated in vacuo and purified using silica gel chromatography to dihydroisoquinoline-2(1H)-carboxylate (3ae). White solid
1
afford the desired product.
(30.3 mg, 70%). M.p. = 90–91 °C. H NMR (400 MHz, CDCl3) δ
tert-Butyl(E)-1-(2-oxo-4-phenylbut-3-en-1-yl)-3,4-dihydroiso- 7.62–7.45 (br m, 3H), 7.25–7.07 (m, 6H), 6.78 (dd, J = 30.3, 16.1
quinoline-2(1H)-carboxylate (3aa).5d White solid (30.6 mg, Hz, 1H), 5.72 (d, J = 30.6 Hz, 1H), 4.26–3.89 (br m, 1H),
1
81%). M.p. = 88–89 °C. H NMR (400 MHz, CDCl3) δ 7.61–7.53 3.48–3.30 (br m, 1H), 3.17 (dd, J = 14.3, 7.2 Hz, 1H), 3.02–2.78
(m, 3H), 7.43–7.31 (m, 3H), 7.20–7.14 (m, 4H), 6.90–6.66 (m, (br m, 3H), 2.50 (d, J = 7.1 Hz, 2H), 1.88 (septet, J = 6.8 Hz,
1H), 5.71 (d, J = 32.1 Hz, 1H), 4.21–3.88 (br m, 1H), 3.36–3.27 1H), 1.42 (s, 9H), 0.91 (d, J = 6.5 Hz, 6H). 13C NMR (100 MHz,
(br m, 1H), 3.17 (dd, J = 14.5, 7.2 Hz, 1H), 3.08–2.71 (br m, CDCl3) δ 197.7, 197.4, 154.3, 145.0, 143.2, 137.1, 136.9, 134.4,
3H), 1.42 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 197.6, 197.4, 134.2, 132.2, 131.9, 129.8, 129.7, 129.0, 128.7, 128.3, 127.2,
154.5, 154.3, 143.1, 143.0, 137.0, 136.9, 134.4, 134.3, 130.6, 127.0, 126.9, 126.4, 125.6, 125.4, 80.3, 79.9, 52.0, 51.6, 48.6,
130.4, 129.0, 128.8, 128.4, 127.1, 127.0, 126.9, 126.5, 126.4, 48.3, 45.3, 39.3, 37.6, 30.2, 28.3, 22.3. IR (thin film): 2923,
126.3, 80.4, 52.0, 51.6, 48.7, 48.5, 39.4, 37.7, 28.4. IR (thin 1685, 1601, 1524, 1416, 1364, 1295, 1161, 1119, 1094, 961, 865,
film): 2925, 1687, 1609, 1417, 1365, 1332, 1297, 1165, 1121, 760 cm−1. HRMS (ESI) m/z calculated for C28H35NO3Na [M +
962, 757, 692 cm−1
.
HRMS (ESI) m/z calculated for Na]+: 456.2509; found: 456.2509.
tert-Butyl(E)-1-(4-(4-(tert-butyl)phenyl)-2-oxobut-3-en-1-yl)-
C24H27NO3Na [M + Na]+: 400.1883; found: 400.1883.
tert-Butyl(E)-1-(4-(4-chlorophenyl)-2-oxobut-3-en-1-yl)-3,4-dihy- 3,4-dihydroisoquinoline-2(1H)-carboxylate (3af). White gum
1
droisoquinoline-2(1H)-carboxylate (3ab). Yellow gum (24.26 mg, (32.1 mg, 74%). H NMR (400 MHz, CDCl3) δ 7.61–7.40 (br m,
62%). 1H NMR (400 MHz, CDCl3) δ 7.67–7.35 (m, 3H), 5H), 7.21–7.17 (m, 4H), 6.83–6.72 (m, 1H), 5.71 (d, J = 32.4 Hz,
7.25–7.06 (m, 6H), 6.83–6.72 (m, 1H), 5.72 (d, J = 32.7 Hz, 1H), 1H), 4.25–3.88 (br m, 1H), 3.50–3.30 (m, 1H), 3.18 (dd, J = 14.4,
4.29–3.83 (br m, 1H), 3.56–3.26 (br m, 1H), 3.17 (dd, J = 14.5, 7.0 Hz, 1H), 3.02–2.77 (br m, 3H), 1.43 (s, 9H), 1.32 (s, 9H). 13
C
7.2 Hz, 1H), 3.03–2.78 (br m, 3H), 2.37 (s, 3H), 1.43 (s, 9H). 13
C
NMR (100 MHz, CDCl3) δ 197.6, 197.4, 154.5, 154.2, 153.9,
NMR(100 MHz, CDCl3) δ 197.5, 197.3, 154.5, 154.2, 143.1, 143.1, 143.0, 137.1, 136.9, 134.4, 134.2, 131.8, 131.5, 129.0,
143.0, 141.1, 140.8, 137.0, 136.9, 134.3, 134.2, 131.8, 131.6, 128.7, 128.2, 127.2, 127.0, 126.8, 126.4, 126.0, 125.8, 125.7,
129.7, 129.6, 129.0, 128.7, 128.3, 127.1, 126.9, 126.8, 126.3, 125.5, 80.3, 79.8, 51.9, 51.5, 48.5, 48.3, 39.4, 37.6, 34.9, 31.1,
126.2, 125.5, 125.3, 80.3, 79.9, 51.9, 51.5, 48.5, 48.3, 39.3, 37.5, 28.3. IR (thin film): 2963, 1686, 1603, 1415, 1364, 1328, 1233,
28.3, 21.5. IR (thin film): 2926, 1685, 1603, 1416, 1365, 1234, 1163, 1119, 962, 865, 821, 752 cm−1. HRMS (ESI) m/z calcu-
1162, 1120, 1095, 961, 865, 758 cm−1. HRMS (ESI) m/z calcu- lated for C28H36NO3 [M + H]+: 434.2690; found: 434.2687.
lated for C25H29NO3Na [M + Na]+: 400.2040; found: 400.2042.
tert-Butyl(E)-1-(4-(4-fluorophenyl)-2-oxobut-3-en-1-yl)-3,4-dihy-
tert-Butyl(E)-1-(4-(4-ethylphenyl)-2-oxobut-3-en-1-yl)-3,4-dihy- droisoquinoline-2(1H)-carboxylate (3ag). White solid (32.4 mg,
1
droisoquinoline-2(1H)-carboxylate (3ac). Yellow gum (29.2 mg, 82%). M.p. = 88–89 °C. H NMR (400 MHz, CDCl3) δ 7.59–7.47
72%). 1H NMR (400 MHz, CDCl3) δ 7.61–7.46 (br m, 3H), (m, 3H), 7.17–7.05 (m, 6H), 6.73 (dd, J = 41.7, 16.1 Hz, 1H),
7.23–7.16 (m, 6H), 6.83–6.72 (m, 1H), 5.72 (d, J = 32.6 Hz, 1H), 5.70 (d, J = 32.8 Hz, 1H), 4.23–3.88 (br m, 1H), 3.49–3.29 (b rm,
4.25–3.89 (br m, 1H), 3.51–3.31 (m, 1H), 3.17 (dd, J = 14.4, 7.2 1H), 3.18–3.13 (m, 1H), 3.01–2.77 (br m, 3H), 1.41 (s, 9H). 13C
Hz, 1H), 3.03–2.78 (br m, 3H), 2.67 (q, 7.5 Hz, 2H), 1.43 (s, NMR (100 MHz, CDCl3) δ 197.4, 197.1, 163.9 (d, J = 249.0 Hz),
9H), 1.25 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 154.6, 154.2, 141.7, 141.6, 137.0, 136.8, 134.4, 134.2, 130.6 (d, J
197.7, 197.4, 154.6, 154.3, 147.5, 147.2, 143.2, 143.1, 137.1, = 5.0 Hz), 130.3 (d, J = 8.0 Hz), 129.1, 128.8, 126.9, 127.1,
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126.4, 126.2, 125.9, 116.1 (d, J = 22.0 Hz), 80.4, 79.9, 52.0, 51.5, 51.6, 48.6, 48.4, 39.3, 37.5, 28.3. IR (thin film): 2926, 1686,
48.7, 48.6, 39.3, 37.6, 28.3. IR (thin film): 2926, 1683, 1598, 1598, 1511, 1420, 1365, 1250, 1171, 1119, 1031, 961, 825,
1508, 1415, 1365, 1230, 1158, 1120, 1095, 961, 827, 760 cm−1
.
759 cm−1. HRMS (ESI) m/z calculated for C25H30NO4 [M + H]+:
HRMS (ESI) m/z calculated for C24H26NO3FNa [M + Na]+: 408.2169; found: 408.2168.
418.1789; found: 418.1784.
tert-Butyl(E)-1-(4-(4-nitrophenyl)-2-oxobut-3-en-1-yl)-3,4-dihy-
tert-Butyl(E)-1-(4-(4-chlorophenyl)-2-oxobut-3-en-1-yl)-3,4-dihy- droisoquinoline-2(1H)-carboxylate (3al). Yellow gum (19.8 mg,
droisoquinoline-2(1H)-carboxylate (3ah). Yellow gum (32.9 mg, 47%). 1H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 7.6 Hz, 2H),
1
80%). H NMR (400 MHz, CDCl3) δ 7.57–7.45 (m, 3H), 7.35 (d, 7.70–7.53 (m, 3H), 7.18–7.09 (m, 4H), 7.02–6.84 (m, 1H), 5.72 (d,
J = 7.9 Hz, 2H), 7.17–7.15 (m, 4H), 6.94–6.55 (m, 1H), 5.70 (d, J J = 37.3 Hz, 1H), 4.21–3.88 (br m, 1H), 3.49–3.32 (m, 1H),
= 34.5 Hz, 1H), 4.31–3.79 (br m, 1H), 3.52–3.25 (br m, 1H), 3.24–3.17 (m, 1H), 3.08–2.79 (m, 3H), 1.43 (s, 9H). 13C NMR
3.16–3.13 (m, 1H), 3.06–2.73 (br m, 3H), 1.41 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 197.0, 154.8, 154.3, 148.6, 141.0, 140.6,
(100 MHz, CDCl3) δ 197.4, 197.1, 154.6, 154.2, 141.5, 141.4, 139.8, 139.6, 136.6, 134.4, 131.0, 130.4, 129.8, 129.5, 128.9, 127.1,
136.9, 136.8, 136.5, 136.2, 134.4, 134.2, 133.1, 132.9, 129.5, 127.0, 126.5, 124.1, 123.6, 123.5, 80.5, 80.2, 52.0, 51.5, 49.1, 39.3,
129.3, 129.1, 128.8, 128.6, 127.1, 126.9, 126.8, 126.5, 126.4, 37.7, 28.4. IR (thin film): 2975, 1683, 1595, 1519, 1415, 1342,
80.3, 80.0, 51.9, 51.5, 48.8, 48.7, 39.3, 37.6, 28.3; IR (thin film): 1234, 1161, 1119, 961, 860, 742 cm−1. HRMS (ESI) m/z calculated
2975, 1687, 1609, 1491, 1417, 1365, 1234, 1164, 1120, 1089, for C24H26N2O5Na [M + Na]+: 445.1734; found: 445.1750.
961, 810, 761 cm−1
.
HRMS (ESI) m/z calculated for
tert-Butyl(E)-1-(4-(2-fluorophenyl)-2-oxobut-3-en-1-yl)-3,4-
dihydroisoquinoline-2(1H)-carboxylate (3am). Yellow gum
(23.7 mg, 60%). H NMR (400 MHz, CDCl3) δ 7.74–7.55 (br m,
C24H26NO3ClNa [M + Na]+: 434.1493; found: 434.1487.
1
tert-Butyl(E)-1-(4-(4-bromophenyl)-2-oxobut-3-en-1-yl)-3,4-
dihydroisoquinoline-2(1H)-carboxylate (3ai). White solid 2H), 7.36 (s, 1H), 7.23–7.08 (m, 6H), 6.92–6.82 (m, 1H), 5.71 (d, J
1
(34.1 mg, 75%). M.p. = 93–94 °C. H NMR (400 MHz, CDCl3) δ = 31.6 Hz, 1H), 4.22–3.92 (br m, 1H), 3.50–3.31 (m, 1H),
7.54–7.39 (br m, 5H), 7.16–7.06 (br m, 4H), 6.85–6.71 (m, 1H), 3.23–3.13 (m, 1H), 3.06–2.78 (br m, 3H), 1.42 (s, 9H). 13C NMR
5.70 (d, J = 34.2 Hz, 1H), 4.21–3.88 (br m, 1H), 3.48–3.31 (m, (100 MHz, CDCl3) δ 197.7, 197.5, 161.5 (d, J = 252.0 Hz), 154.3,
1H), 3.16–3.12 (m, 1H), 3.02–2.76 (br m, 3H), 1.41 (s, 9H). 13C 137.0, 135.5, 135.0, 134.5, 132.1 (d, J = 8.0 Hz), 129.1, 128.9 (d, J
NMR (100 MHz, CDCl3) δ 197.2, 197.0, 154.5, 154.1, 141.5, = 2.0 Hz), 127.2, 126.9, 126.4, 124.6 (d, J = 8.0 Hz), 122.5 (d, J =
141.3, 136.8, 136.7, 134.3, 134.2, 133.5, 133.2, 132.2, 132.0, 10.0 Hz), 116.3 (d, J = 21.0 Hz), 80.4, 79.9, 52.0, 51.6, 48.5, 48.2,
131.4, 129.7, 129.6, 129.0, 128.7, 127.0, 126.9, 126.5, 126.3, 39.3, 37.6, 28.3; IR (thin film): 2928, 1685, 1609, 1416, 1365,
124.8, 124.5, 80.3, 79.9, 51.9, 51.4, 48.7, 48.6, 39.2, 37.5, 28.4, 1230, 1160, 1120, 1094, 961, 861, 755 cm−1. HRMS (ESI) m/z cal-
28.3. IR (thin film): 2927, 1686, 1609, 1488, 1417, 1365, 1296, culated for C24H26NO3FNa [M + Na]+: 418.1789; found: 418.1777.
1163, 1120, 1071, 1009, 961, 805, 761 cm−1. HRMS (ESI) m/z
tert-Butyl(E)-1-(4-(2-chlorophenyl)-2-oxobut-3-en-1-yl)-3,4-
calculated for C24H27NO3Br [M
456.1155.
+
H]+: 456.1169; found: dihydroisoquinoline-2(1H)-carboxylate (3an). Yellow gum
1
(21.8 mg, 53%). H NMR (600 MHz, CDCl3) δ 7.39–7.25 (br m,
tert-Butyl(E)-1-(4-(4-iodophenyl)-2-oxobut-3-en-1-yl)-3,4-dihy- 3H), 7.17–7.06 (br m, 5H), 7.01 (d, J = 6.9 Hz, 1H), 6.34 (dd, J =
droisoquinoline-2(1H)-carboxylate (3aj). Yellow solid (30.2 mg, 47.6, 8.0 Hz, 1H), 5.60 (d, J = 32.8 Hz, 1H), 4.07–3.87 (br m,
1
60%). M.p. = 90–91 °C. H NMR (400 MHz, CDCl3) δ 7.73–7.61 1H), 3.17 (dt, J = 75.2, 6.4 Hz, 1H), 2.87–2.70 (br m, 3H), 2.63
(m, 2H), 7.47 (dd, J = 30.9, 16.1 Hz, 1H), 7.26–7.17 (br m, 6H), (d, J = 10.0 Hz, 1H), 1.46 (s, 9H). 13C NMR (150 MHz, CDCl3) δ
6.80 (dd, J = 43.3, 15.6 Hz, 1H), 5.69 (d, J = 33.6 Hz, 1H), 199.9, 199.6, 154.5, 154.2, 137.0, 136.8, 136.3, 134.4, 134.3,
4.21–3.87 (br m, 1H), 3.45–3.29 (m, 1H), 3.17–3.13 (m, 1H), 134.1, 133.9, 133.3, 131.2, 131.0, 130.4, 130.3, 130.2, 130.0,
3.01–2.78 (br m, 3H), 1.41 (s, 9H). 13C NMR (150 MHz, CDCl3) 129.4, 129.3, 129.0, 128.7, 127.1, 126.9, 126.8, 126.54, 126.51,
δ 197.2, 197.0, 154.6, 154.2, 141.7, 141.5, 138.2, 138.1, 136.9, 126.3, 80.4, 79.9, 51.7, 51.4, 50.4, 50.3, 38.8, 37.5, 28.4. IR (thin
136.8, 134.4, 133.8, 131.4, 129.8, 129.7, 129.3, 129.1, 128.9, film): 2975, 1687, 1417, 1365, 1296, 1234, 1163, 1121, 1051,
128.7, 127.1, 126.9, 126.7, 126.4, 96.9, 80.3, 79.9, 51.9, 51.5, 962, 863, 754 cm−1
48.8, 48.7, 39.3, 37.6, 28.3. IR (thin film): 2925, 1686, 1608, C24H26NO3ClNa [M + Na]+: 434.1493; found: 434.1493.
. HRMS (ESI) m/z calculated for
1484, 1418, 1365, 1235, 1164, 1121, 1005, 803, 761 cm−1.HRMS
tert-Butyl(E)-1-(4-(2-bromophenyl)-2-oxobut-3-en-1-yl)-3,4-
(ESI) m/z calculated for C24H26NO3INa [M + Na]+: 526.0850; dihydroisoquinoline-2(1H)-carboxylate (3ao). Yellow gum
1
found: 526.0850.
tert-Butyl(E)-1-(4-(4-methoxyphenyl)-2-oxobut-3-en-1-yl)-3,4-
(23.7 mg, 52%). H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 6.7
Hz, 1H), 7.33–7.01 (br m, 8H), 6.32 (dd, J = 49.9, 12.2 Hz, 1H),
dihydroisoquinoline-2(1H)-carboxylate (3ak). Yellow gum 5.60 (d, J = 31.9 Hz, 1H), 4.08–3.87 (br m, 1H), 3.26–2.05 (m,
1
(20.8 mg, 51%). H NMR (400 MHz, CDCl3) δ 7.59–7.48 (br m, 1H), 2.87–2.61 (br m, 4H), 1.46 (s, 9H). 13C NMR (100 MHz,
3H), 7.22–7.15 (m, 4H), 6.91 (d, J = 8.2 Hz, 2H), 6.69 (dd, J = CDCl3) δ 200.1, 199.8, 154.5, 154.2, 139.1, 138.5, 136.8, 136.7,
33.2, 16.0 Hz, 1H), 5.71 (d, J = 32.6 Hz, 1H), 4.22–3.78 (br m, 136.0, 135.8, 134.5, 134.3, 132.6, 132.4, 131.2, 131.1, 130.3,
4H), 3.47–3.27 (br m, 1H), 3.15 (dd, J = 14.3, 7.3 Hz, 1H), 130.2, 129.0, 128.7, 127.20, 127.15, 126.9, 126.8, 126.3, 123.2,
3.00–2.77 (br m, 3H), 1.41 (s, 9H). 13C NMR (100 MHz, CDCl3) 80.4, 79.9, 51.7, 51.4, 50.4, 50.2, 38.8, 37.5, 28.4, 28.2. IR (thin
δ 197.6, 197.3, 161.7, 161.5, 154.6, 154.3, 142.94, 142.85, 137.1, film): 2974, 1684, 1415, 1364, 1232, 1159, 1119, 1025, 961, 862,
137.0, 134.4, 134.3, 130.1, 129.1, 128.7, 127.2, 127.0, 126.98, 751, 657 cm−1. HRMS (ESI) m/z calculated for C24H27NO3Br
126.86, 126.4, 124.3, 124.1, 114.5, 114.3, 80.3, 79.8, 55.4, 52.0, [M + H]+: 456.1169; found: 456.1149.
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tert-Butyl(E)-1-(4-(2-(methoxycarbonyl)phenyl)-2-oxobut-3-
en-1-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate
tert-Butyl(E)-1-(4-(3-fluoro-4-methoxyphenyl)-2-oxobut-3-en-
(3ap). 1-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (3at). yellow
Yellow gum (35.7 mg, 82%). 1H NMR (400 MHz, CDCl3) δ gum (25.9 mg, 61%). 1H NMR (400 MHz, CDCl3) δ 7.46 (dd, J =
8.51–8.44 (m, 1H), 7.99 (s, 1H), 7.63–7.44 (br m, 3H), 7.30–7.15 31.7, 16.0 Hz, 1H), 7.29–7.16 (br m, 6H), 6.95 (t, J = 8.4 Hz,
(br m, 4H), 6.62 (dd, J = 34.1, 16.2 Hz, 1H), 5.76 (d, J = 29.2 Hz, 1H), 6.66 (dd, J = 35.6, 15.9 Hz, 1H), 5.69 (d, J = 31.9 Hz, 1H),
1H), 4.23–3.93 (br m, 1H), 3.92 (s, 3H), 3.51–3.33 (m, 1H), 4.20–3.88 (br m, 1H), 3.91 (s, 3H), 3.45–3.29 (br m, 1H), 3.14
3.27–3.07 (m, 2H), 2.97–2.79 (m, 2H), 1.41 (s, 9H). 13C NMR (dd, J = 14.4, 7.3 Hz, 1H), 3.00–2.77 (br m, 3H), 1.41 (s, 9H).
(100 MHz, CDCl3) δ 198.0, 167.0, 154.2, 142.4, 141.7, 137.0, 13C NMR (100 MHz, CDCl3) δ 197.3, 197.1, 154.6, 154.2, 152.3
136.7, 136.5, 134.5, 134.3, 132.5, 132.4, 131.0, 130.8, 129.9, (d, J = 246.0 Hz), 149.8 (d, J = 11.0 Hz), 141.7, 141.6, 137.0,
129.6, 129.4, 129.0, 128.7, 127.9, 127.7, 127.3, 127.0, 126.8, 136.8, 134.4, 134.3, 129.1, 128.7, 127.9 (d, J = 8.0 Hz), 127.5 (d,
126.3, 80.2, 79.8, 52.4, 52.2, 51.6, 47.3, 39.1, 37.4, 28.3. IR (thin J = 6.0 Hz), 126.9, 127.2, 127.0, 126.4, 125.9 (d, J = 2.0 Hz),
film): 2975, 1718, 1687, 1609, 1418, 1365, 1253, 1163, 1122, 125.3, 125.0, 114.8 (d, J = 19.0 Hz), 113.1, 80.3, 79.9, 56.2, 51.9,
1079, 963, 757 cm−1
C26H30NO5H [M + H]+: 436.2118; found: 436.2118.
. HRMS (ESI) m/z calculated for 51.5, 48.7, 48.6, 39.3, 37.5, 28.3. IR (thin film): 2933, 1682,
1601, 1513, 1417, 1365, 1275, 1160, 1120, 1023, 960, 732 cm−1
.
tert-Butyl(E)-1-(2-oxo-4-(m-tolyl)but-3-en-1-yl)-3,4-dihydroiso- HRMS (ESI) m/z calculated for C25H28NO4FNa [M + Na]+:
quinoline-2(1H)-carboxylate (3aq). Yellow gum (32.1 mg, 82%). 448.1895; found: 448.1895.
1H NMR (400 MHz, CDCl3) δ 7.62–7.31 (br m, 3H), 7.19–7.15
tert-Butyl(E)-1-(4-(2,4-dichlorophenyl)-2-oxobut-3-en-1-yl)-
(m, 5H), 6.85–6.72 (m, 1H), 5.73 (d, J = 32.1 Hz, 1H), 4.31–3.81 3,4-dihydroisoquinoline-2(1H)-carboxylate (3au). Yellow gum
(br m, 1H), 3.51–3.31 (br m, 1H), 3.20–3.15 (m, 1H), 3.08–2.72 (22.3 mg, 50%). 1H NMR (400 MHz, CDCl3) δ 7.40–7.35 (m,
(br m, 3H), 2.37 (s, 3H), 1.44 (s, 9H). 13C NMR (100 MHz, 2H), 7.17–7.08 (br m, 5H), 6.96 (d, J = 12.4 Hz, 1H), 6.40 (dd, J
CDCl3) δ 197.5, 197.3, 154.3, 154.2, 143.2, 143.1, 138.5, 138.4, = 55.7, 12.3 Hz, 1H), 5.61 (d, J = 37.5 Hz, 1H), 4.09–3.87 (br m,
137.0, 136.8, 134.3, 134.2, 131.4, 131.2, 129.7, 129.5, 128.9, 1H), 3.35–3.11 (m, 1H), 2.94–2.66 (br m, 4H), 1.45 (s, 9H). 13C
128.8, 128.7, 128.3, 127.1, 126.9, 126.8, 126.3, 126.2, 126.0, NMR (100 MHz, CDCl3) δ 199.0, 154.6, 154.2, 136.7, 136.1,
125.6, 125.5, 80.2, 79.8, 51.9, 51.5, 48.6, 48.2, 39.3, 37.5, 135.7, 135.4, 135.1, 134.4, 134.1, 132.5, 132.1, 131.9, 130.3,
28.3, 21.4, 21.2. IR (thin film): 2926, 1684, 1605, 1416, 1364, 130.0, 129.2, 129.0, 128.8, 127.1, 127.0, 126.8, 126.4, 80.5, 80.0,
1232, 1159, 1119, 1095, 961, 755, 691 cm−1. HRMS (ESI) m/z 51.7, 51.3, 50.9, 39.0, 37.7, 28.4. IR (thin film): 2927,
calculated for C25H29NO3Na [M + Na]+: 400.2040; found: 1 685 1415, 1364, 1233, 1159, 1120, 1097, 1050, 961, 862,
400.2043.
tert-Butyl(E)-1-(4-(3-fluorophenyl)-2-oxobut-3-en-1-yl)-3,4-dihy- + Na]+: 468.1104; found: 468.1104.
751 cm−1. HRMS (ESI) m/z calculated for C24H25NO3Cl2Na [M
droisoquinoline-2(1H)-carboxylate (3ar). Yellow gum (30.8 mg,
tert-Butyl(E)-1-(2-oxo-6-phenylhex-3-en-1-yl)-3,4-dihydroiso-
78%). 1H NMR (400 MHz, CDCl3) δ 7.57–7.46 (m, 1H), quinoline-2(1H)-carboxylate (3av). Yellow gum (18.2 mg, 45%).
7.34–7.08 (m, 8H), 6.79 (dd, J = 36.6, 15.9 Hz, 1H), 5.70 (d, J = 1H NMR (600 MHz, CDCl3) δ 7.30–7.28 (m, 2H), 7.22–7.12 (m,
31.9 Hz, 1H), 4.21–3.89 (br m, 1H), 3.50–3.30 (br m, 1H), 7H), 6.89–6.79 (m, 1H), 6.22–6.14 (m, 1H), 5.60 (d, J = 32.1 Hz,
3.16–3.14 (m, 1H), 3.03–2.78 (br m, 3H), 1.42 (s, 9H). 13C NMR 1H), 4.16–3.84 (br m, 1H), 3.41–3.21 (m, 1H), 3.05–2.76 (br m,
(100 MHz, CDCl3) δ 197.3, 197.1, 163.0 (d, J = 246.0 Hz), 154.6, 6H), 2.54 (q, J = 4.8 Hz, 2H), 1.44 (s, 9H). 13C NMR (150 MHz,
154.2, 141.5, 141.4, 136.9 (d, J = 5.0 Hz), 134.4, 134.3, 130.6 (d, CDCl3) δ 197.6, 154.2, 146.8, 146.5, 140.8, 140.6, 137.0, 134.4,
J = 7.0 Hz), 129.1, 128.8, 127.5, 127.2 (d, J = 10.0 Hz), 127.0, 131.4, 130.8, 129.0, 128.5, 128.4, 127.2, 127.0, 126.9, 126.33,
126.4, 124.4, 117.5 (d, J = 20.0 Hz), 114.5 (d, J = 22.0 Hz), 80.4, 126.27, 80.3, 79.8, 52.0, 51.6, 47.6, 39.3, 37.5, 34.4, 34.2, 28.4. IR
80.0, 51.9, 51.5, 48.8, 48.7, 39.3, 37.6, 28.3. IR (thin film): 2928, (thin film): 2928, 1687, 1416, 1364, 1332, 1295, 1233, 1160,
1686, 1612, 1417, 1365, 1236, 1163, 1121, 1096, 962, 865, 757, 1119, 961, 747, 699 cm−1. HRMS (ESI) m/z calculated for
681 cm−1. HRMS (ESI) m/z calculated for C24H26NO3FNa [M + C26H31NO3Na [M + Na]+: 428.2196; found: 428.2195.
Na]+: 418.1789; found: 418.1781.
tert-Butyl(E)-1-(4-(3-chlorophenyl)-2-oxobut-3-en-1-yl)-3,4-dihy-
tert-Butyl(E)-1-(2-oxodec-3-en-1-yl)-3,4-dihydroisoquinoline-2
(1H)-carboxylate (3aw). Yellow gum (21.9 mg, 54%). 1H NMR
droisoquinoline-2(1H)-carboxylate (3as). Yellow gum (32.1 mg, (400 MHz, CDCl3) δ 7.15–7.12 (m, 4H), 6.90–6.77 (m, 1H),
78%). 1H NMR (400 MHz, CDCl3) δ 7.53–7.33 (br m, 5H), 6.18–6.10 (m, 1H), 5.62 (d, J = 28.7 Hz, 1H), 4.17–3.86 (m, 1H),
7.17–7.15 (br m, 4H), 6.79 (dd, J = 35.2, 16.0 Hz, 1H), 5.70 (d, J 3.42–3.23 (m, 1H), 3.08–2.74 (br m, 4H), 2.20 (q, J = 6.9 Hz,
= 32.4 Hz, 1H), 4.21–3.88 (br m, 1H), 3.47–3.29 (m, 1H), 2H), 1.44–1.41 (m, 11H), 1.34–1.24 (m, 6H), 0.88 (t, J = 6.8 Hz,
3.19–3.13 (m, 1H), 3.03–2.77 (br m, 3H), 1.42 (s, 9H). 13C NMR 3H). 13C NMR (100 MHz, CDCl3) δ 197.7, 154.2, 148.3, 137.1,
(100 MHz, CDCl3) δ 197.2, 197.0, 154.6, 154.2, 141.3, 141.1, 134.3, 130.9, 130.4, 129.0, 128.6, 127.1, 127.0, 126.8, 126.3,
136.8, 136.7, 136.5, 136.1, 134.9, 134.8, 134.4, 134.2, 130.4, 80.2, 79.7, 51.9, 47.5, 39.3, 37.5, 32.5, 31.6, 28.8, 28.3, 28.0,
130.2, 129.1, 128.7, 127.9, 127.4, 127.2, 126.9, 127.1, 126.5, 22.5, 14.0. IR (thin film): 2927, 1688, 1625, 1415, 1364, 1332,
126.4, 80.3, 79.9, 51.8, 51.5, 48.8, 48.7, 39.3, 37.6, 28.6, 28.4, 1295, 1231, 1161, 1119, 960, 749 cm−1. HRMS (ESI) m/z calcu-
28.3. IR (thin film): 2927, 1683, 1611, 1416, 1364, 1233, 1160, lated for C24H36NO3 [M + H]+: 386.2690; found: 386.2691.
1119, 1096, 962, 864, 760, 683 cm−1. HRMS (ESI) m/z calcu-
tert-Butyl(E)-6,7-dimethoxy-1-(2-oxo-4-phenylbut-3-en-1-yl)-
lated for C24H26NO3ClNa [M
434.1474.
+
Na]+: 434.1493; found: 3,4-dihydroisoquinoline-2(1H)-carboxylate (3ba). White solid
1
(32.8 mg, 75%). M.p. = 89–90 °C. H NMR (400 MHz, CDCl3) δ
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7.60–7.53 (m, 3H), 7.38 (s, 3H), 6.86–6.72 (m, 2H), 6.61 (s, 1H),
5.65 (d, J = 39.0 Hz, 1H), 4.24–3.93 (br m, 1H), 3.84 (s, 6H),
Acknowledgements
3.44–3.26 (m, 1H), 3.21–3.16 (m, 1H), 3.01–2.68 (br m, 3H), We are grateful for the financial support from the National
1.43 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 197.6, 154.4, Natural Science Foundation of China (NSFC-21702162 and
154.1, 147.8, 147.5, 143.1, 142.8, 134.4, 134.2, 130.5, 130.3, NSFC-21971206) and the Scientific Research Program Funded
128.9, 128.8, 128.2, 126.5, 126.2, 126.0, 111.3, 110.0, 109.69, by Shaanxi Provincial Education Department (Program No.
80.2, 79.7, 55.9, 55.8, 51.5, 51.0, 48.5, 48.4, 39.1, 37.5, 28.2. 17JK0788).
IR (thin film): 2931, 1683, 1608, 1515, 1417, 1364, 1254,
1160, 1097, 974, 860, 752, 695 cm−1. HRMS (ESI) m/z
calculated for C26H31NO5Na [M + Na]+: 460.2094; found:
460.2093.
Notes and references
tert-Butyl(E)-5-bromo-1-(2-oxo-4-phenylbut-3-en-1-yl)-3,4-
1 For selected reviews, see: (a) S. R. Harutyunyan, T. Hartog,
K. Geurts, A. J. Minnaard and B. L. Feringa, Chem. Rev.,
2008, 108, 2824; (b) K. Zheng, X. Liu and X. Feng, Chem.
Rev., 2018, 118, 7586; (c) G. Desimoni, G. Faita and
P. Quadrelli, Chem. Rev., 2018, 118, 2080; (d) Y.-Q. Zou,
F. M. Hörmann and T. Bach, Chem. Soc. Rev., 2018, 47, 278.
dihydroisoquinoline-2(1H)-carboxylate (3ca). Yellow gum
1
(27.8 mg, 61%). H NMR (400 MHz, CDCl3) δ 7.55–7.40 (br m,
7H), 7.18–7.06 (m, 2H), 6.86–6.74 (m, 1H), 5.73 (d, J = 36.8 Hz,
1H), 4.31–4.03 (br m, 1H), 3.39–2.89 (br m, 5H), 1.42 (s, 9H).
13C NMR (150 MHz, CDCl3) δ 197.1, 197.0, 154.1, 143.4, 143.2,
139.6, 134.2, 131.0, 130.8, 130.6, 129.6, 129.0, 128.9, 128.7, 2 For selected examples of 1,2-addition of α,β-unsaturated
128.4, 127.6, 126.2, 125.5, 80.6, 80.2, 51.7, 51.1, 48.5, 48.2,
38.6, 37.1, 28.3. IR (thin film): 2975, 1686, 1608, 1418, 1365,
1323, 1229, 1162, 1104, 963, 751, 690 cm−1. HRMS (ESI) m/z
calculated for C24H26NO3BrNa [M + Na]+: 478.0988; found:
478.0988.
ketones, see: (a) Y. Hanzawa, N. Tabuchi, K. Saito,
S. Noguchi and T. Taguchi, Angew. Chem., Int. Ed., 1999, 38,
2395; (b) N. Halland, R. G. Hazell and K. A. Jørgensen,
J. Org. Chem., 2002, 67, 8331; (c) M. L. Kantam, S. Laha,
J. Yadav, B. M. Choudary and B. Sreedhar, Adv. Synth. Catal.,
2006, 348, 867.
tert-Butyl(E)-7-nitro-1-(2-oxo-4-phenylbut-3-en-1-yl)-3,4-dihy-
droisoquinoline-2(1H)-carboxylate (3da). Yellow gum (8.9 mg, 3 For selected reviews and examples of the Baylis–Hillman
21%). 1H NMR (400 MHz, CDCl3) δ 8.14 (s, 1H), 8.01 (d, J =
8.3 Hz, 1H), 7.61–7.55 (m, 3H), 7.40–7.28 (m, 4H), 6.82–6.79
(m, 1H), 5.82 (d, J = 22.7 Hz, 1H), 4.28–3.97 (br m, 1H),
3.49–3.30 (m, 1H), 3.24–3.18 (m, 1H), 3.13–2.89 (br m, 3H),
1.44 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 196.4, 154.4,
reaction of α,β-unsaturated ketones, see: (a) D. Basavaiah,
A. J. Rao and T. Satyanarayana, Chem. Rev., 2003, 103, 811;
(b) D. Basavaiah, B. S. Reddy and S. S. Badsara, Chem. Rev.,
2010, 110, 5447; (c) D. Basavaiah and G. Veeraraghavaiah,
Chem. Soc. Rev., 2012, 41, 68.
154.0, 146.5, 143.6, 142.2, 138.6, 134.2, 130.8, 130.1, 129.0, 4 For selected reviews and examples of Michael addition of
128.4, 125.9, 122.3, 121.8, 80.9, 80.5, 51.5, 51.0, 48.2, 47.7,
38.5, 36.9, 28.3; IR (thin film): 2929, 1685, 1608, 1521, 1413,
1343, 1157, 1132, 1089, 968, 741, 690 cm−1; HRMS (ESI) m/z
calculated for C24H26N2O5Na [M + Na]+: 445.1734; found:
445.1734.
α,β-unsaturated ketones, see: (a) T. Hayashi and
K. Yamasaki, Chem. Rev., 2003, 103, 2829; (b) A. Alexakis,
J. E. Bäckvall, N. Krause, O. Pàmies and M. Diéguez, Chem.
Rev., 2008, 108, 2796; (c) S. R. Harutyunyan, T. Hartog,
K. Geurts, A. J. Minnaard and B. L. Feringa, Chem. Rev.,
2008, 108, 2824.
Di-tert-butyl(E)-1-(2-methylene-4-phenylbut-3-en-1-ylj)-3,4-
dihydro-1H-pyrido[3,4-b]indole-2,9-dicarboxylate (3ea). Yellow 5 (a) J. D. Scott and R. M. Williams, Chem. Rev., 2002, 102,
1
gum (40.3 mg, 78%). H NMR (400 MHz, CDCl3) δ 8.10 (d, J =
7.3 Hz, 1H), 7.82 (d, J = 15.9 Hz, 1H), 7.59 (s, 2H), 7.38–7.23 (br
m, 6H), 6.97 (dd, J = 59.4, 16.5 Hz, 1H), 6.43 (dd, J = 67.4, 8.6
Hz, 1H), 4.54–4.27 (br m, 1H), 3.55–3.23 (br m, 2H), 2.96–2.64
1669; (b) G. A. Cordell, Phytochemistry, 2013, 91, 29;
(c) M. Iranshahy, R. J. Quinn and M. Iranshahi, RSC Adv.,
2014, 4, 15900; (d) H. Zheng, Y. Dong, L. Li, B. Sun, L. Liu,
H. Yuan and H. Lou, J. Med. Chem., 2016, 59, 5063.
(br m, 3H), 1.76 (s, 9H), 1.37 (s, 9H). 13C NMR (100 MHz, 6 For selected reviews and examples of the CDC reaction of
CDCl3) δ 197.1, 197.6, 154.7, 154.2, 150.2, 150.1, 143.2, 142.9,
135.8, 135.6, 134.8, 134.7, 130.4, 130.1, 128.9, 128.7, 128.4,
128.2, 126.5, 125.7, 124.5, 124.4, 122.9, 122.8, 118.1, 116.1,
115.8, 115.4, 84.5, 84.4, 80.3, 79.9, 50.1, 49.1, 45.3, 44.7, 37.0,
35.5, 28.3, 20.7. IR (thin film): 2976, 1723, 1691, 1609, 1455,
1415, 1367, 1311, 1159, 1140, 1117, 991, 747, 695 cm−1. HRMS
(ESI) m/z calculated for C31H37N2O5 [M + H]+: 517.2697; found:
517.2719.
tetrahydroisoquinolines, see: (a) D. Cheng and W. Bao, Adv.
Synth. Catal., 2008, 350, 1263; (b) X.-Z. Shu, X.-F. Xia,
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2009, 74, 7464; (c) K. Alagiri, P. Devadig and K. R. Prabhu,
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S. Kobayashi, Org. Lett., 2014, 16, 2346; (e) Z. Xie, L. Liu,
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Chem., Int. Ed., 2014, 53, 3904; (f) W. Chen, H. Zheng,
X. Pan, Z. Xie, X. Zan, B. Sun, L. Liu and H. Lou, Tetrahedron
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Adv., 2014, 4, 60075; (h) S. Sun, C. Li, P. E. Floeancig, H. Lou
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Conflicts of interest
There are no conflicts to declare.
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