Construction of Indoline-Fused Tetrahydroisoquinolines through a Domino Coupling Reaction Catalyzed by CuCoFe Layered Double Hydroxide

Article abstract of DOI:10.1021/acs.orglett.1c02059

A convenient catalytic protocol for efficiently constructing indoline-fused tetrahydroisoquinolines based on CuCoFe layered double hydroxide (LDH) has been described. Preliminary mechanistic studies show that indoline-fused tetrahydroisoquinolines are produced via domino coupling/cyclization reactions between tetrahydroisoquinolines and active methylene compounds, including malononitrile, malonates, and analogues. CuCoFe-LDH can accelerate the Csp3-Csp3 and Csp3-Csp2 formation reactions in a single step. The research thus presents a unique opportunity to develop a synthetic methodology for N-containing polycyclic compounds.

Full text of DOI:10.1021/acs.orglett.1c02059

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Letter
Construction of Indoline-Fused Tetrahydroisoquinolines through a
Domino Coupling Reaction Catalyzed by CuCoFe Layered Double
Hydroxide
Weiyou Zhou, Anwei Wang, Zhenji Kong, Xiaoting Tian, Zhenzhen Xia, Zhihui Zhang, Mingyang He,*
Qun Chen, and Shixin Sun*
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ABSTRACT: A convenient catalytic protocol for efficiently construct-
ing indoline-fused tetrahydroisoquinolines based on CuCoFe layered
double hydroxide (LDH) has been described. Preliminary mechanistic
studies show that indoline-fused tetrahydroisoquinolines are produced
via domino coupling/cyclization reactions between tetrahydroisoquino-
lines and active methylene compounds, including malononitrile,
malonates, and analogues. CuCoFe-LDH can accelerate the Csp3−Csp3 and Csp3−Csp2 formation reactions in a single step. The
research thus presents a unique opportunity to develop a synthetic methodology for N-containing polycyclic compounds.
Scheme 1. Methods for the Synthesis of Indoline-Fused
Tetrahydroisoquinoline
-Containing polycyclic compounds make up an important
class for bioactive substances, natural products, and
N
medicine.1 Construction of various polycyclic compounds
through domino or cascade reactions is always an effective
method,2 featuring a high efficiency, a simple process, and easy
handling. However, the reaction systems are always complex,
and multiple metals, noble ligands, and base or acid additives are
required. Developing simple and efficient catalytic systems for
organic transformation is quite attractive for chemists.
Tetracyclic indoline-fused tetrahydroisoquinoline is an
important tetracyclic structure for the synthesis of natural
product cryptaustoline and related alkaloids.3 The motif is
generally synthesized via the intramolecular coupling of aryl
chlorides or bromides with amines,3,4 using multi-step-
synthesized substrates and complex catalytic systems (Scheme
1i). Maciver et al. reported a catalytic enantioselective
electrocyclic cascade for the construction of multiple rings
with specific reactants and a phase catalyst (Scheme 1ii).5 The
module structure has also been reported by Mahoney and
Fillion,6 where N-aziridinyl imines were introduced as the
substrates using [Rh2(5S-MEPY)4] [5S-MEPY = methyl-2-
oxopyrrolidine-5(S)-carboxylate]7 as the catalyst (Scheme 1iii).
In our recent research on the heterogeneously catalytic coupling
reaction between N-phenyltetrahydroisoquinoline (1a) and
malononitrile (2a), an interesting domino coupling/cyclization
product (3aa) (Scheme 1) was observed under the catalysis of
CuCoFe layered double hydroxide (CuCoFe-LDH).8 To
confirm the structure of the product, single crystals of 3aa
were subjected to X-ray analysis. To the best of our knowledge,
the transformation and the formation of tetracyclic indoline-
fused tetrahydroisoquinoline have not been reported. This
protocol will provide a very simple and efficient method for the
direct functionalization of tertiary α-C−H and the construction
Received: June 24, 2021
Published: August 11, 2021
https://doi.org/10.1021/acs.orglett.1c02059
© 2021 American Chemical Society
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of indoline-fused tetrahydroisoquinolines from readily available
and cost-effective precursors under mild reaction conditions.
We initially focused on the reaction between 1a and 2a over
CuCoFe-LDH.9 After the systematic optimization of the
reaction conditions, a good 65% isolated yield of 3aa could be
obtained.10 The stability of the catalyst has also been studied,
and the results indicated that the present CuCoFe-LDH catalyst
is highly durable and quite stable in structure (Figures S5 and
S6). Then the scope of tetrahydroisoquinolines bearing various
substituents was first investigated (Scheme 2). The substrates
to that of 3ca. As expected, a similar result was observed for the
substrate with two methyls at sites 2 and 5 (1h), and an only 8%
yield of 3ha could be isolated. Surprisingly, substrate 1i with an
ethyl located at the ortho site could be well tolerated, giving a
good 58% yield of 3ia. Substrates with a halogen group located at
the para site of the phenyl could proceed smoothly and offer
moderate to good yields (3ja−3la). With regard to the reaction
time, it can be deduced that electron-withdrawing substituents
on the phenyl accelerate the reaction. On the contrary, when the
N atom is linked with high-electron density groups, the reaction
was significantly suppressed (3ma and 3na). Subsequently,
some N-phenyltetrahydroisoquinoline derivatives with substitu-
ents at site 6 or 7 were tested. For the substrate with a methyl at
site 6 (3oa), an excellent 90% yield was obtained. However,
substrates with one or two methoxyls at sites 6 and 7 offered
relatively lower yields (3pa and 3qa), but with short reaction
times. These observations indicated that electron-donating
groups in isoquinoline improve the reaction activity. Then, N-
benzyl-N-ethylaniline (1r) as an acyclic amine was examined in
the reaction, and only the de-ethyl product (4r) could be
observed, which might be due to its high sensitivity to oxidation.
Subsequently, some other nucleophiles were tested (Scheme
3). Dimethyl malonate (2b), ethyl cyanoacetate (2c), and 1,3-
indanedione (2d) could react with 1a smoothly (3ab, 3ac, and
3ad, respectively) and gave moderate to good yields. Then,
various tetrahydroisoquinoline derivatives were investigated
using 2c as the nucleophile, and satisfactory results could be
obtained (3dc, 3jc, 3oc, and 3pc). Consistent with that of 2a,
when 1m was used as the substrate, no coupling/cyclization
a
Scheme 2. Scope of Tetrahydroisoquinolines
a
Scheme 3. Scope of Nucleophiles
a
Reaction conditions: 0.5 mmol of 1, 1.5 mmol of 2a, 0.2 g of
b
CuCoFe-LDH, 2 mL of 1,4-dioxane, 80 °C, oxygen atmosphere. The
main byproduct was 2-[2-(2,5-dimethylphenyl)-1,2,3,4-tetrahydroiso-
quinolin-1-yl]malononitrile (4ha).
with electron-donating groups at the para site of phenyl could be
well tolerated, and good yields of the corresponding products
were obtained (3aa−3da). However, tetrahydroisoquinoline
with a methyl located at the ortho site gave a quite low yield
(3ea) for the corresponding product, and the coupling product
(4ea) formed as the main byproduct. On the contrary, 1f with a
methoxyl at the same site could give a moderate yield of the
product (3fa) with a prolonged reaction time. The result for 1e
might be ascribed to steric hindrance. When methoxyl is located
at the meta site (1g), 3ga was obtained in 47% yield, comparable
a
Reaction conditions: 0.5 mmol of 1, 1.5 mmol of 2, 0.2 g of
CuCoFe-LDH, 2 mL of 1,4-dioxane, 80 °C, oxygen atmosphere.
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product 3mc could be detected. Considering the substituents
with different electronic properties, these observations further
indicated that electron-withdrawing substituents in the phenyl
and electron-donating groups in the isoquinoline could enhance
the reactivity. 1,3-Indanedione could also react with these
substrates well to form spiro structures with relatively lower
yields, which might be due to its poor nucleophilic ability and
high steric hindrance (3jd, 3od, and 3pd). However, ethyl
acetoacetate, benzoyl acetonitrile, p-trifluoromethylphenylace-
tonitrile, or acetylacetone was not reactive under the catalytic
system presented here.
The aforementioned results have shown that indoline-fused
tetrahydroisoquinolines can be constructed from N-phenyl-
tetrahydroisoquinolines and appropriate nucleophiles over an
available CuCoFe-LDH catalyst. Furthermore, the trans-
formation of the geminal dinitriles in the resultant indoline-
fused tetrahydroisoquinoline 3aa has been tried (Scheme 4).
the substrate. Furthermore, the surface copper valence for
CuCoFe-LDH was identified through XPS spectra. As illustrated
in Figure S8, the core fitting peaks of Cu 2p3/2 could be fitted at
932.7 and 934.6 eV, indicating the mixed valence of Cu+ and
Cu2+.12 To identify the effect of the valence of copper species,
CuCl and CuCl2 were tested in the reaction (entries 8 and 9,
respectively). Excellent catalytic activity for the transformation
of 1a could be obtained, but the selectivity for 3aa were quite
low, giving 6a as the main product (78% yield), consistent with
previously reported results.13 In contrast, only a trace of 6a was
observed in the case of CuCoFe-LDH. These results suggested
that Cu species (both Cu+ and Cu2+) accelerate the trans-
formation of 1a, but the combination of Cu, Co, and Fe is
essential for the formation of 3aa. Therefore, a synergistic effect
among Cu, Co, and Fe probably exists in this transformation.
Radical scavengers [BHT (2,6-di-tert-butyl-4-methylphenol)
and CCl3Br] significantly suppressed the reaction (entries 10
and 11, respectively), implying that a radical intermediate
probably forms during the reaction.
Scheme 4. Transformation of the Resultant Indoline-Fused
Tetrahydroisoquinoline 3aa
In the classical CDC transformation, iminium has been
proven to be the intermediate,14 which was also verified by the
MS-ESI analysis of the reaction filtrate without any nucleophile
(Figure S9) in the study presented here. Kinetic isotopic effect
(KIE) experiments were also conducted to gain further
information about the catalytic domino reaction (Scheme 5).
Scheme 5. Kinetic Isotopic Effect Experiments
Oxidative treatment of 3aa under the CuCl2/TBHP (tert-butyl
hydroperoxide) oxidation conditions led to methyl 2-[1-oxo-
3,4-dihydroisoquinolin-2(1H)-yl]benzoate (5a) with a high
yield of 81%. To the best of our knowledge, the cleavage mode
has not been reported, and the structure of 5a has been
confirmed by X-ray analysis. Then, we carried out the reductive
elimination in toluene using AIBN (azodiisobutyronitrile) and
tributyltin hydride as a reducing system,11 and an excellent 93%
yield of 5,6-dihydroindolo[2,1-a]isoquinoline-12-carbonitrile
(5b) was obtained. These transformations will facilitate further
application of the protocol presented here. Moreover, when the
reaction of 1a was scaled up to 1.05 g (5.0 mmol), a satisfactory
55% yield of 3aa could be obtained (Scheme S3), demonstrating
the good practicability of the protocol.
To elucidate the catalytic behavior of CuCoFe-LDH, a series
of controlled experiments were carried out (Table S3). In the
absence of a catalyst, 67% conversion and 12% selectivity to 3aa
were detected (entry 2), indicating the catalytic function of
CuCoFe-LDH. The results of the experiments performed under
different atmospheres (entries 3 and 4) suggested that oxygen is
crucial for the efficient transformation. To identify the active
catalytic site, some hydrotalcite-like compounds with different
cations in the brucite layers have been investigated (XRD
patterns can be found in Figure S7). Although CuMgAl-LDH
and CuCoAl-LDH exhibited excellent catalytic activity for the
transformation of 1a (entries 5 and 6, respectively), the
selectivity to 3aa was quite low. In the case of Co2Fe-LDH,
both conversion and selectivity were markedly low (entry 7),
implying that Cu species played an important role in activating
When 2-phenyl-1,2,3,4-tetrahydroisoquinoline-1-d (1a-d1) was
subjected to the reaction, an intramolecular isotopic kH/kD of 3.3
was calculated from the ratio of the signal intensity in the GC-
MS analysis (Scheme 5i). This observation suggested a more
important contribution from C−H bond cleavage than from
electron transfer in the rate-determining step,15 and a hydrogen
atom transfer (HAT) process should occur predominantly for
C−H bond cleavage. An obvious secondary kinetic isotope
effect on the benzene ring (intermolecular kH/kD = 2.1)
indicated that C−C bond formation occurs before C−H bond
cleavage (Scheme 5ii).16
Then, we focused on the catalytic behavior of CuCoFe-LDH
in the transformation of 4aa to 3aa (Table S4). Without a
catalyst, an only 13% conversion and 67% selectivity were
observed (entry 2),17 indicating the catalytic activity of
CuCoFe-LDH in the cyclization. The reaction proceeded well
with decreased reactivity in the absence of oxygen (entry 3),
which might be due to the adsorbed oxygen on the catalyst. The
control experiments with different catalysts suggested that the
Cu+ was crucial for this coupling between Csp3−H and Csp2−H.
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Without oxygen, CuCl offered only quite low conversion and
selectivity for 3aa (entry 9), implying that Cu2+ superoxide
(Cu2+OO•) might form by the reaction of Cu+ with O2 during
the reaction,18 which then could activate the α-Csp3−H of the
geminal dinitriles via a HAT process. In addition, radical
scavenges (BHT and CCl3Br) could significantly suppress the
reaction (entries 10 and 11, respectively), further verifying the
speculation presented above.
On the basis of the findings presented above and previous
studies,14b,18,19 we proposed a reaction pathway for the domino
reaction between N-phenyl-tetrahydroquinolines and malono-
nitrile over CuCoFe-LDH (Scheme 6). In the reaction, Cu+ in
In conclusion, we have developed an unprecedented layered
double hydroxide-catalyzed domino coupling/cyclization re-
action to construct ring-annulated 5,6,12,12a-tetrahydroindolo-
[2,1-a]isoquinoline motifs in moderate to good yields, where
CuCoFe-LDH acted as an efficient catalyst for the dual
functionalization of both a C(sp3)−H bond and a C(sp2)−H
bond in a single step. To the best of our knowledge, these are the
first examples of N-aryltetrahydroisoquinolines participating in
direct annulation reactions with nucleophiles in this fashion
under any conditions, and these products have all previously
been unreported. This chemistry also displays the potential of
layered double hydroxides as efficient heterogeneous catalysts
for the domino transformation via convenient ways, for the
construction of complex heterocyclic scaffolds.
Scheme 6. Proposed Reaction Pathway
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c02059.
Experimental procedures, optimization tables, character-
ization data, and X-ray crystallographic data (PDF)
Accession Codes
CCDC 2083420−2083421 contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/data_request/cif, or by email-
ing data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road, Cam-
bridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
■
Mingyang He − Jiangsu Key Laboratory of Advanced Catalytic
Materials and Technology, Changzhou University, Changzhou
213164, P. R. China; orcid.org/0000-0001-7409-0756;
Email: hemy_cczu@126.com
Shixin Sun − School of Chemical & Environmental Engineering,
Yancheng Teachers University, Yancheng 224002, P. R. China;
Email: asunshixin@163.com
CuCoFe-LDH can react with molecular O2 to afford Cu2+OO•
species. The Cu2+OO• then abstracts a hydrogen from the α-C-
H of N-phenyl-tetrahydroquinoline to afford α-amino radical
intermediate 7, which is transformed into an iminium ion
intermediate (8) via further loss of an electron. The reaction can
also be initiated by SET (single-electron transfer) from the
nitrogen to Cu2+ in CuCoFe-LDH, and the resulting amine
radical species is transformed into 8 via loss of a H atom from
site 1 (or a combination of an electron and H+). Intermediate 8,
which is stabilized by the N-aryl group,20 then is trapped by
malononitrile as a nucleophile to produce 4aa. Next, coupling
product 4aa is transformed into a neutral radical intermediate
(9) primarily via a HAT process over CuCoFe-LDH, followed
by an intramolecular radical arylation to furnish the cyclo-
hexadienyl radical (10). Zhu et al. have reported that this
pathway from 9 to 10 is reversible in the absence of oxygen,21
and the oxygen atmosphere in this system should accelerate the
formation of 10, consistent with the results presented here.
Finally, cyclization product 3aa forms via proton and electron
transfer, or a HAT process from cyclohexadienyl radical H to
formed Cu2+OO• under certain conditions. On the contrary,
the C−H at site 3 of the tetrahydroisoquinoline can also cleave
to produce iminium cation (8′), which can be trapped by
malononitrile to produce byproduct 4′aa, which has been
isolated in a 12% yield under the selected conditions.
Intermediate 8 may be in equilibrium with 8′, also leading to
the formation of 8′.
Authors
Weiyou Zhou − Jiangsu Key Laboratory of Advanced Catalytic
Materials and Technology, Changzhou University, Changzhou
213164, P. R. China; orcid.org/0000-0003-0149-0921
Anwei Wang − Jiangsu Key Laboratory of Advanced Catalytic
Materials and Technology, Changzhou University, Changzhou
213164, P. R. China
Zhenji Kong − Jiangsu Key Laboratory of Advanced Catalytic
Materials and Technology, Changzhou University, Changzhou
213164, P. R. China
Xiaoting Tian − Jiangsu Key Laboratory of Advanced Catalytic
Materials and Technology, Changzhou University, Changzhou
213164, P. R. China
Zhenzhen Xia − Jiangsu Key Laboratory of Advanced Catalytic
Materials and Technology, Changzhou University, Changzhou
213164, P. R. China
Zhihui Zhang − Jiangsu Key Laboratory of Advanced Catalytic
Materials and Technology, Changzhou University, Changzhou
213164, P. R. China
Qun Chen − Jiangsu Key Laboratory of Advanced Catalytic
Materials and Technology, Changzhou University, Changzhou
213164, P. R. China
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(8) A Chinese patent has been submitted: Zhou, W. Y.; Wang, A. W.;
Kong, Z. J.; Xia, Z. Z.; He, M. Y.; Chen, Q. Synthesis of a Polycyclic
Compound Containing Dihydroindole Structure. CN112645948A,
2021.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c02059
Notes
(9) The structural analysis of the CuCoFe-LDH catalyst can be found
The authors declare no competing financial interest.
in the Supporting Information.
(10) Various reaction conditions, including reaction temperature,
solvent, and the ratio of 2a to 1a, were optimized. The detailed data can
be found in the Supporting Information.
(11) Gerlach, U. Synthesis of Tricyclic Cyano-substituted Tetrahy-
droquinolines by Radical Decyanation of Geminal Dinitriles.
Tetrahedron Lett. 1995, 36, 5159−5162.
(12) Yan, J. C.; Chen, Y.; Qian, L. B.; Gao, W. G.; Ouyang, D.; Chen,
M. F. Heterogeneously Catalyzed Persulfate with a CuMgFe Layered
Double Hydroxide for the Degradation of Ethylbenzene. J. Hazard.
Mater. 2017, 338, 372−380.
(13) (a) Li, Z. P.; Li, C. J. Highly Efficient CuBr-Catalyzed Cross-
Dehydrogenative Coupling (CDC) between Tetrahydroisoquinolines
and Activated Methylene Compounds. Eur. J. Org. Chem. 2005, 2005,
3173−3176. (b) Li, Z.; Pi, Y. X.; Xu, D. Y.; Li, Y.; Peng, W. C.; Zhang,
G. L.; Zhang, F. B.; Fan, X. B. Utilization of MoS2 and Graphene to
Enhance the Photocatalytic Activity of Cu2O for Oxidative C−C Bond
Formation. Appl. Catal., B 2017, 213, 1−8.
(14) (a) Yang, Q.; Zhang, L.; Ye, C.; Luo, S. Z.; Wu, L. Z.; Tung, C. H.
Visible-Light-Promoted Asymmetric Cross-Dehydrogenative Coupling
of Tertiary Amines to Ketones by Synergistic Multiple Catalysis. Angew.
Chem., Int. Ed. 2017, 56, 3694−3698. (b) Boess, E.; Schmitz, C.;
Klussmann, M. A Comparative Mechanistic Study of Cu-Catalyzed
Oxidative Coupling Reactions with N-Phenyltetrahydroisoquinoline. J.
Am. Chem. Soc. 2012, 134, 5317−5325.
(15) (a) Murahashi, S.-I.; Nakae, T.; Terai, H.; Komiya, N.
Ruthenium-Catalyzed Oxidative Cyanation of Tertiary Amines with
Molecular Oxygen or Hydrogen Peroxide and Sodium Cyanide: sp3 C−
H Bond Activation and Carbon−Carbon Bond Formation. J. Am.
Chem. Soc. 2008, 130, 11005−11012. (b) Wang, Y. D.; Hedman, B.;
Hodgson, K. O.; Stack, T. D. P. Catalytic Galactose Oxidase Models:
Biomimetic Cu(II)-Phenoxyl-Radical Reactivity. Science 1998, 279,
537−540.
ACKNOWLEDGMENTS
■
This work was supported by the Advanced Catalysis and Green
Manufacturing Collaborative Innovation Center of Changzhou
University, a project funded by the Priority Academic Program
Development of Jiangsu Higher Education Institutions (PAPD),
the Jiangsu Key Laboratory of Advanced Catalytic Materials and
Technology (BM2012110), the Natural Science Foundation for
Colleges and Universities in Jiangsu Province (20KJA530003),
the Changzhou Key Technology R&D Program for Social
Development (CE20205054), and the Qinglan Project of
Jiangsu Province.
REFERENCES
■
(1) (a) Faust, R.; Garratt, P. J.; Jones, R.; Yeh, L.-K.; Tsotinis, A.;
Panoussopoulou, M.; Calogeropoulou, T.; Teh, M.-T.; Sugden, D.
Mapping the Melatonin Receptor. 6. Melatonin Agonists and
Antagonists Derived from 6H-Isoindolo[2,1-a]indoles, 5,6-
Dihydroindolo[2,1-a]isoquinolines, and 6,7-Dihydro-5H-benzo[c]-
azepino[2,1-a]indoles. J. Med. Chem. 2000, 43, 1050−1061. (b) Mao,
Q.; Zhang, B. J.; Li, W. W.; Tian, S.; Shui, W. Q.; Ye, N. Identification of
Novel 1-O-Substituted Aporphine Analogues as Potent 5-HT2C
Receptor Agonists. ACS Chem. Neurosci. 2020, 11, 549−559.
(2) (a) Andreansky, E. S.; Blakey, S. B. An Iminium Ion Cascade
Annulation Strategy for the Synthesis of Akuammiline Alkaloid
Pentacyclic Core Structures. Org. Lett. 2016, 18, 6492−6495. (b) Yu,
S. Y.; Zhang, Z. H.; Gao, Y.; Mo, L.; Wang, S. Z.; Yao, Z. J. Asymmetric
Cascade Annulation Based on Enantioselective Oxa-Diels−Alder
Cycloaddition of in Situ Generated Isochromenyliums by Cooperative
Binary Catalysis of Pd(OAc)2 and (S)-Trip. J. Am. Chem. Soc. 2013,
135, 11402−11407. (c) He, M.; Chen, N.; Liu, L. L.; Zhu, Y. Q.; Li, Q.;
Li, H. G.; Lang, M.; Wang, J.; Peng, S. Y. Synthesis of 3-
Azabicyclo[m.2.0] Ring Systems via a Copper-Catalyzed Cascade
Reaction of Diazo Compounds with 1,n-Allenynes. J. Org. Chem. 2020,
85, 4418−4429.
(16) Yang, X. L.; Guo, J. D.; Lei, T.; Chen, B.; Tung, C. H.; Wu, L. Z.
Oxidative Cyclization Synthesis of Tetrahydroquinolines and Reduc-
tive Hydrogenation of Maleimides under Redox-Neutral Conditions.
Org. Lett. 2018, 20, 2916−2920.
(17) The main byproducts were 1a and 6a.
(18) Itoh, S. Developing Mononuclear Copper−Active-Oxygen
Complexes Relevant to Reactive Intermediates of Biological Oxidation
Reactions. Acc. Chem. Res. 2015, 48, 2066−2074.
(3) (a) Kametani, T.; Ogasawara, K. Benzyne reaction. Part I. Total
Syntheses of ( )-Cryptaustoline and ( )-Cryptowoline by the
Benzyne Reaction. J. Chem. Soc. C 1967, 0, 2208−2212. (b) Meyers,
A. I.; Sielecki, T. M. Total Synthesis of the Dibenzopyrrocoline Alkaloid
S-(+)-Cryptaustoline. Revision of Absolute Configuration due to an
Unusual Inversion in Stereochemistry. J. Am. Chem. Soc. 1991, 113,
2789−2790. (c) Meyers, A. I.; Sielecki, T. M.; Crans, D. C.; Marshman,
R. W.; Nguyen, H. (−)-Cryptaustoline: its Synthesis, Revision of
Absolute Stereochemistry, and Mechanism of Inversion of Stereo-
chemistry. J. Am. Chem. Soc. 1992, 114, 8483−8489.
(19) Some selected examples: (a) Li, Z. P.; Li, C. J. Highly Efficient
Copper-Catalyzed Nitro-Mannich Type Reaction: Cross-Dehydrogen-
ative-Coupling between sp3 C−H Bond and sp3 C−H Bond. J. Am.
Chem. Soc. 2005, 127, 3672−3673. (b) Baslé, O.; Li, C. J. Copper-
catalyzed Aerobic Phosphonation of sp3 C−H Bonds. Chem. Commun.
2009, 27, 4124−4126. (c) Li, Z. P.; Bohle, D. S.; Li, C. J. Cu-catalyzed
Cross-dehydrogenative Coupling: A Versatile Strategy for C−C Bond
Formations Via the Oxidative Activation of sp3 C−H Bonds. Proc. Natl.
Acad. Sci. U. S. A. 2006, 103, 8928−8933.
(4) (a) Omar-Amrani, R.; Thomas, A.; Brenner, E.; Schneider, R.;
Fort, Y. Efficient Nickel-Mediated Intramolecular Amination of Aryl
Chlorides. Org. Lett. 2003, 5, 2311−2314. (b) Vincze, Z.; Bíró, A. B.;
Csékei, M.; Timári, G.; Kotschy, A. The Palladium-Catalyzed
Preparation of Condensed Tetracyclic Heterocycles and their
Application to the Synthesis of rac-Mangochinine. Synthesis 2006, 8,
1375−1385.
(20) Tsang, A. S. K.; Hashmi, A. S. K.; Comba, P.; Kerscher, M.; Chan,
B.; Todd, M. H. N-Aryl Groups Are Ubiquitous in Cross-Dehydrogen-
ative Couplings Because They Stabilize Reactive Intermediates. Chem. -
Eur. J. 2017, 23, 9313−9318.
(21) Zhu, S. Q.; Das, A.; Bui, L.; Zhou, H. J.; Curran, D. P.; Rueping,
M. Oxygen Switch in Visible-Light Photoredox Catalysis: Radical
Additions and Cyclizations and Unexpected C−C-Bond Cleavage
Reactions. J. Am. Chem. Soc. 2013, 135, 1823−1829.
(5) Maciver, E. E.; Knipe, P. C.; Cridland, A. P.; Thompson, A. L.;
Smith, M. D. Catalytic Enantioselective Electrocyclic Cascades. Chem.
Sci. 2012, 3, 537−540.
(6) Mahoney, S. J.; Fillion, E. N-Fused Indolines through Non-
Carbonyl-Stabilized Rhodium Carbenoid C−H Insertion of N-
Aziridinyl Imines. Chem. - Eur. J. 2012, 18, 68−71.
(7) Doyle, M. P. New Catalysts and Methods for Highly
Enantioselective Metal Carbene Reactions. Pure Appl. Chem. 1998,
70, 1123−1128.
6325
https://doi.org/10.1021/acs.orglett.1c02059
Org. Lett. 2021, 23, 6321−6325