Multicomponent Synthesis of α-Branched Tertiary and Secondary Amines by Photocatalytic Hydrogen Atom Transfer Strategy

Article abstract of DOI:10.1021/acs.orglett.1c01412

A multicomponent carbonyl alkylative amination reaction is described. A variety of N-arylamines, aldehydes, and hydrocarbons have been examined as reaction substrates using tetrabutylammonium decatungstate as photocatalyst, providing the corresponding α-branched tertiary and secondary amines in good to moderate yields. The reaction proceeds through the generation of alkyl radicals by a light-promoted hydrogen atom transfer process followed by free radical addition to iminium ions generated in situ.

Full text of DOI:10.1021/acs.orglett.1c01412

pubs.acs.org/OrgLett
Letter
Multicomponent Synthesis of α‑Branched Tertiary and Secondary
Amines by Photocatalytic Hydrogen Atom Transfer Strategy
Xu-Kuan Qi, Lin Guo, Li-Juan Yao, Han Gao, Chao Yang,* and Wujiong Xia*
Cite This: Org. Lett. 2021, 23, 4473−4477
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: A multicomponent carbonyl alkylative amination reaction is described. A variety of N-arylamines, aldehydes, and
hydrocarbons have been examined as reaction substrates using tetrabutylammonium decatungstate as photocatalyst, providing the
corresponding α-branched tertiary and secondary amines in good to moderate yields. The reaction proceeds through the generation
of alkyl radicals by a light-promoted hydrogen atom transfer process followed by free radical addition to iminium ions generated in
situ.
Scheme 1. Methods for the Preparation of α-Branched
Tertiary Amines via Iminium Ion Intermediate
ulticomponent reactions (MCRs) are convergent
Mreactions in which three or more starting materials
react to generate a product with essentially all or most of the
atoms contributing to the newly formed product.1 The one-pot
process allows rapid and efficient access to highly diverse
synthesis, making the MCRs more atomically and procedurally
economical. In particular, these integral benefits make MCRs
highly attractive for natural product and pharmaceuticals
synthesis, heterocyclic chemistry, as well as bioconjugation.2
Considering the fact that branched amines are privileged
structural motifs present in bioactive molecules and drug
candidates,3 the synthesis of α-branched tertiary and secondary
amines by MCRs would be of considerable interest.
Carbonyl reductive amination is an important method for
the preparation of tertiary amines, which comprises two
elementary steps: the condensation of secondary amines with
aldehydes or ketones to form iminium ions and the subsequent
reduction by hydride reagents (Scheme 1a).4 Due to the slow
condensation of secondary amines with ketones, this strategy
suffers from limitations for the synthesis of branched variants,
requiring activating reagents or multistep synthesis.5 Coupling
of an alkyl fragment with in situ generated iminium ion stands
for a more desirable strategy for the multicomponent synthesis
of branched amines,6 while this route has not been fully
investigated, as commonly used alkyl organometallic reagents
are rarely compatible with in situ iminium ion formation.7
Until recently, the Gaunt group has made significant
breakthrough to this research area.8 They reported a
photocatalytic carbonyl alkylative amination (CAA) protocol
for the multicomponent synthesis of α-branched tertiary
alkylamines through the addition of alkyl radicals to all-alkyl
iminium ions using iodoalkanes as alkyl sources and
stoichiometric silanes as reducing agents (Scheme 1b).8c
As part of our ongoing interest in developing viable
protocols for novel photochemical transformations,9 we are
interested in exploring a multicomponent carbonyl alkylative
amination protocol directly using unactivated alkanes as alkyl
Received: April 25, 2021
Published: May 24, 2021
https://doi.org/10.1021/acs.orglett.1c01412
© 2021 American Chemical Society
Org. Lett. 2021, 23, 4473−4477
4473

Organic Letters
pubs.acs.org/OrgLett
Letter
source. Such a synthetic pathway of generating carbon-center
radicals via a photocatalytic hydrogen atom transfer (HAT)
process is very attractive in organic synthesis, as there is no
need for prior functionalization. The most straightforward way
to implement the HAT process is to use a photocatalyst, which
could be excited by light to achieve the excited state followed
by hydrogen atom abstraction from simple alkanes.10 Among
these photocatalysts, tetrabutylammonium decatungstate
(TBADT; [W10O32] (nBu4N)4) is widely used by scientists
due to its high reactivity, unique site selectivity, and simple
preparation from inexpensive precursors.10d−f We envisaged
that under appropriate photochemical conditions, the use of
TBADT would facilitate the generation of alkyl radicals, which
will be further added to iminium ions formed in situ by
secondary amines and aldehydes to achieve the preparation of
α-branched tertiary amines (Scheme 1).
With the optimized conditions in hand, we next sought to
examine the scope of this multicomponent photocatalytic
reaction. At the outset, various secondary arylamines were
examined with 2a and 3a under the standard conditions,
affording the desired N-aryl tertiary amine products in good to
moderate yields (Scheme 2, 4a−4m). Diarylamine with methyl
(4b, 4d, 4f, and 4g), bromine (4c), and fluorine (4e) at
different positions on the aromatic ring (ortho, meta, and para
positions) was tolerated well. Moderate yields were obtained
for N-benzyl- and N-methylanilines as reaction substrates
(4h−4k), and our method was also applicable to indoline and
tetrahydroquinoline substrates (4l−4m), which are ubiquitous
in pharmaceutically relevant molecules.11
In addition, an excellent tolerance of functional groups was
observed during the subsequent investigation of the aldehydes
scope (Scheme 2, 4n−4x). Studies have showed that aliphatic
aldehydes bearing acyclic hydrocarbons were all converted into
the corresponding α-branched tertiary amines 4n−4t in good
to moderate yields. Branched aldehydes also worked well
under the optimal conditions (4u−4x). To highlight the
practicability of our method, a reaction of 3-methylbutanal
with 1a and 3a was successfully performed on a larger scale
(3.0 mmol), affording the desired product 4r in 75% yield.
Furthermore, the scope with respect to aliphatic C−H
compounds was investigated (Scheme 2, 4y−4kk). A wide
range of hydrocarbons proved to be competent coupling
partners for the three-component reaction. Cycloalkanes with
different ring sizes were effectively transformed into the
corresponding products 4y−4aa. Norbornane was predom-
inantly functionalized on the ethylene bridge (4bb), while the
sterically hindered tertiary C−H bonds showed almost no
reactivity despite their relatively low BDEs.12 The structures of
4bb as well as 4a was confirmed by X-ray crystallography. It is
worth noting that the functionalization of toluene derivatives
occurred exclusively on the primary benzylic C−H bonds, and
the corresponding tertiary amine products 4cc−4ii were
isolated in moderate to excellent yields. Tetrasubstituted
alkene 3jj was further examined to successfully furnish the
desired product 4jj in 29% yield. Additionally, α-heteroatom
C−H bonds were found to be effectively functionalized with
excellent regioselectivity. For example, tert-butyl methyl ether
(3kk) was functionalized at the α-oxy position to afford 4kk in
74% yield.
The scope with respect to the multicomponent synthesis of
α-branched secondary amines from aniline derivatives was
further explored (Scheme 3). These reactions were performed
in the presence of 2 mol % of TBADT using acetic acid as
additive. Various aniline derivatives, including substrates
bearing methyl (5a) and halogen (5b−5d) substituents,
underwent the photocatalytic multicomponent reaction with
benzaldehyde and cyclohexane (3a) to furnish the correspond-
ing secondary amines products 6a−6d in good yields.
Aromatic, heteroaromatic, and aliphatic aldehydes were
successfully employed as necessary components affording the
desired products 6e−6h in 62−78% yields. Furthermore, the
multicomponent reaction of aniline and benzaldehyde with a
variety of hydrocarbons, including cyclohexane (6i), 2,3-
dimethyl-2-butene (6j), 1,4-dioxane (6k), and p-xylene (6l),
proceeded smoothly under the standard conditions. Notably,
aldehyde substrate 2a can also serve as a suitable C−H
component to react with benzaldehyde, affording the two-
component reaction product 7 in 78% yield (Scheme 4).
Our study commenced with the three-component reaction
of diphenylamine (1a), cyclohexanecarbaldehyde (2a), and
cyclohexane (3a), as shown in Table 1. In the presence of 3
a
Table 1. Optimization of Reaction Conditions
TBADT
(mol %)
additive
(1.1 equiv)
solvent (0.1
M)
b
entry
yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
3
3
3
3
3
3
2
1
3
3
BF3·Et2O
TMSOTf
TFA
dry MeCN
dry MeCN
dry MeCN
dry MeCN
dry DCM
benzonitrile
dry MeCN
dry MeCN
dry MeCN
dry MeCN
dry MeCN
dry MeCN
40
58
trace
82
62
trace
63
48
TBSOTf
TBSOTf
TBSOTf
TBSOTf
TBSOTf
TBSOTf
TBSOTf
TBSOTf
c
10
d
3
a
Standard conditions: 1a (0.20 mmol), 2a (1.5 equiv), 3a (40 equiv),
TBSOTf (1.1 equiv), TBADT (3 mol %), 4 Å MS (30 mg), MeCN
b
(0.1 M), 10 W 390 nm LEDs, 24 h. Yields of isolated products.
c
d
Without 4 Å MS molecular sieves. Without light.
mol % of TBADT as photocatalyst, BF3·Et2O as additive, and 4
Å molecular sieves in dry MeCN under irradiation of near-
ultraviolet light (390 nm, 10 W LEDs), the desired α-branched
tertiary amine product 4a was isolated in 40% yield (entry 1).
Different additives were first investigated (entries 2−4). To
our delight, tert-butyldimethylsilyl trifluoromethanesulfonate
(TBSOTf) was found to be the optimal candidate with 82%
yield of 4a (entry 4). The use of other solvents was explored
but provided no improvement over dry acetonitrile (entries 5
and 6). Moreover, reducing the photocatalyst loading led to a
drop of reaction efficiency (entries 7 and 8), and the reaction
in the absence of 4 Å molecular sieves resulted in much lower
yields (entry 9). As anticipated, control experiments revealed
that light, photocatalyst, as well as additive are essential for this
transformation (entries 10−12).
4474
https://doi.org/10.1021/acs.orglett.1c01412
Org. Lett. 2021, 23, 4473−4477

Organic Letters
pubs.acs.org/OrgLett
Letter
a,b
Scheme 2. Scope of the Multicomponent Photocatalytic Synthesis of α-Branched Tertiary Amines
a
Standard conditions: 1 (0.20 mmol), 2 (0.30 mmol, 1.5 equiv), 3 (8.0 mmol, 40 equiv), TBSOTf (0.22 mmol, 1.1 equiv), TBADT (0.006 mmol, 3
b
c
mol %), 4 Å MS (30−50 mg), dry MeCN (0.1 M), 10 W 390 nm LEDs, 24 h. Yields of isolated products. Reaction was performed on the 3.0
mmol scale for 36 h. 3 (6.0 mmol, 30 equiv). 3 (4.0 mmol, 20 equiv). 3 (2.0 mmol, 10 equiv).
d
e
f
In order to understand the mechanism of this multi-
component reaction, 2,2,6,6-tetramethyl-1-piperidinyloxy
(TEMPO) as suitable radical scavenger was first subjected to
the standard reaction conditions, and the desired reaction
process was significantly inhibited, indicating that the trans-
formation may undergo a radical pathway (Scheme 5a). To
determine whether the hydrogen atom transfer (HAT) is the
rate-determining step of the whole reaction process, a kinetic
isotope effect (KIE) experiment was further carried out. The
reaction with same amount of 3a and deuterated substrate 3a-
On the basis of the above results and literature reports, a
plausible reaction mechanism for the multicomponent photo-
catalytic synthesis of α-branched tertiary amines was proposed
(Scheme 6). Secondary arylamine 1 and aldehyde 2 first
undergo a fast condensation reaction to in situ generate
iminium ion species I in the presence of additives such as
TBSOTf. In the meantime, photoexcitation of TBADT
produces its excited state, which can abstract hydrogen from
unactivated hydrocarbons 3 to form neutral carbon radical
intermediates II. Then the radical II undergoes a free radical
addition to the iminium ion I to release amine radical cation
III followed by a fast hydrogen atom transfer process. The
formed N-centered cation IV subsequently undergoes
deprotonation process and releases tertiary amine 4 as final
product. The multicomponent synthesis of α-branched
secondary arylamines from aniline derivatives shows a similar
d12 under the standard conditions for 6 h provided a mixture of
4a and isotopically labeled 4a-d12 in 50% yield, in which the
ratio of 4a and 4a-d12 was 3.5 (Scheme 5b). The KIE value
revealed that the step of hydrogen atoms extraction by
photoexcited TBADT might be the rate-determining step of
this transformation.
4475
https://doi.org/10.1021/acs.orglett.1c01412
Org. Lett. 2021, 23, 4473−4477

Organic Letters
pubs.acs.org/OrgLett
Letter
Scheme 3. Scope of the Multicomponent Photocatalytic
Synthesis of α-Branched Secondary Amines
Scheme 6. Proposed Reaction Mechanism
a,b
photocatalyst. The reaction uses cheap and commercially
available alkanes, easily accessible aldehydes, and N-arylamines
as feedstock, showing high synthetic efficiency as well as atom
and step economy. The use of stoichiometric TBSOTf as
additive to promote the in situ formation of iminium ions is
the key to the success of preparing α-branched tertiary amines.
The reaction could be easily scaled up, making the synthetic
methodology suitable for diversity-oriented synthesis in drug
discovery scenarios. Further development of other photo-
catalytic transformations is underway in our laboratory.
a
Standard conditions: 5 (0.20 mmol), 2 (0.30 mmol, 1.5 equiv), 3
(30 equiv), AcOH (0.10 mmol, 0.5 equiv), TBADT (0.004 mmol, 2
mol %), dry MeCN (0.2 M), 10 W 390 nm LEDs, 24 h. Yields of
isolated products. 3 (4.0 mmol, 20 equiv). 3 (2.0 mmol, 10 equiv).
b
c
d
ASSOCIATED CONTENT
■
sı
* Supporting Information
Scheme 4. Reaction of Aniline with
Cyclohexanecarbaldehyde to Form α-Branched Secondary
Amine via Acyl C−H Bond Abstraction
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c01412.
Experimental details, characterization data, and copies of
NMR spectra for all novel compounds (PDF)
Accession Codes
CCDC 2074730−2074731 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
Scheme 5. Investigation of Reaction Mechanism
AUTHOR INFORMATION
Corresponding Authors
■
Chao Yang − State Key Lab of Urban Water Resource and
Environment, School of Science, Harbin Institute of
Technology (Shenzhen), Shenzhen 518055, China;
Email: xyyang@hit.edu.cn
Wujiong Xia − State Key Lab of Urban Water Resource and
Environment, School of Science, Harbin Institute of
Technology (Shenzhen), Shenzhen 518055, China; School of
Chemistry and Chemical Engineering, Henan Normal
University, Xinxiang, Henan 453007, China; orcid.org/
0000-0001-9396-9520; Email: xiawj@hit.edu.cn
reaction character, where anilines and aldehydes rapidly
condense in situ to form N-arylimine intermediates.6a,13
In summary, we have established an efficient multi-
component protocol for the synthesis of α-branched tertiary
and secondary amines using catalytic amount of TBADT as
Authors
Xu-Kuan Qi − State Key Lab of Urban Water Resource and
Environment, School of Science, Harbin Institute of
Technology (Shenzhen), Shenzhen 518055, China
4476
https://doi.org/10.1021/acs.orglett.1c01412
Org. Lett. 2021, 23, 4473−4477

Organic Letters
pubs.acs.org/OrgLett
Letter
Solution Mediated by Nanoscale Zinc Architectures. Angew. Chem.,
Int. Ed. 2011, 50, 924−927. (d) Uraguchi, D.; Kinoshita, N.; Kizu, T.;
Ooi, T. Synergistic Catalysis of Ionic Bronsted Acid and Photo-
sensitizer for a Redox Neutral Asymmetric alpha-Coupling of N-
Arylaminomethanes with Aldimines. J. Am. Chem. Soc. 2015, 137,
13768−13771. (e) Patel, N. R.; Kelly, C. B.; Siegenfeld, A. P.;
Molander, G. A. Mild, Redox-Neutral Alkylation of Imines Enabled by
an Organic Photocatalyst. ACS Catal. 2017, 7, 1766−1770. (f) Jia, J.;
Lefebvre, Q.; Rueping, M. Reductive Coupling of Imines with Redox-
Active Esters by Visible Light Photoredox Organocatalysis. Org. Chem.
Front. 2020, 7, 602−608.
Lin Guo − State Key Lab of Urban Water Resource and
Environment, School of Science, Harbin Institute of
Technology (Shenzhen), Shenzhen 518055, China
Li-Juan Yao − State Key Lab of Urban Water Resource and
Environment, School of Science, Harbin Institute of
Technology (Shenzhen), Shenzhen 518055, China
Han Gao − State Key Lab of Urban Water Resource and
Environment, School of Science, Harbin Institute of
Technology (Shenzhen), Shenzhen 518055, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c01412
(7) (a) Reiber, H. G.; Stewart, T. D. The Tetra Alkyl Methylene
Immonium Salts. J. Am. Chem. Soc. 1940, 62, 3026−3030. (b) Bloch,
R. Additions of Organometallic Reagents to C = N Bonds: Reactivity
and Selectivity. Chem. Rev. 1998, 98, 1407−1438.
Notes
(8) (a) Trowbridge, A.; Reich, D.; Gaunt, M. J. Multicomponent
Synthesis of Tertiary Alkylamines by Photocatalytic Olefin-Hydro-
aminoalkylation. Nature 2018, 561, 522−527. (b) Flodén, N. J.;
Trowbridge, A.; Willcox, D.; Walton, S. M.; Kim, Y.; Gaunt, M. J.
Streamlined Synthesis of C(sp3)-Rich N-Heterospirocycles Enabled
by Visible-Light-Mediated Photocatalysis. J. Am. Chem. Soc. 2019,
141, 8426−8430. (c) Kumar, R.; Floden, N. J.; Whitehurst, W. G.;
Gaunt, M. J. A General Carbonyl Alkylative Amination for Tertiary
Amine Synthesis. Nature 2020, 581, 415−421. (d) Blackwell, J. H.;
Kumar, R.; Gaunt, M. J. Visible-Light-Mediated Carbonyl Alkylative
Amination to All-Alkyl α-Tertiary Amino Acid Derivatives. J. Am.
Chem. Soc. 2021, 143, 1598−1609.
(9) (a) Zhao, Y.; Huang, B.; Yang, C.; Li, B.; Gou, B.; Xia, W.
Photocatalytic Cross-Dehydrogenative Amination Reactions between
Phenols and Diarylamines. ACS Catal. 2017, 7, 2446−2451.
(b) Zhao, Y.; Xia, W. Recent Advances in Radical-Based C−N
Bond Formation via Photo-/Electrochemistry. Chem. Soc. Rev. 2018,
47, 2591−2608. (c) Feng, L.; Guo, L.; Yang, C.; Zhou, J.; Xia, W.
Visible-Light-Induced Palladium-Catalyzed Intermolecular Narasaka-
Heck Reaction at Room Temperature. Org. Lett. 2020, 22, 3964−
3968.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful for financial support from the National Natural
Science Foundation of China (No. 21672047), The Science
a n d T e c h n o l o g y P l a n o f S h e n z h e n
(JCYJ20180306172044124), and the Natural Science Founda-
tion of Guangdong (No. 2020A1515010564). W. X. is grateful
for the Talent Plan of the Pearl River in Guangdong, Starting
up fund from Shenzhen Government and the financial support
from Guangdong Province Covid-19 Pandemic Control
Research Fund (No.2020KZDZX1218). The project was also
supported by the Open Research Fund of the School of
Chemistry and Chemical Engineering, Henan Normal
University.
REFERENCES
■
(1) (a) Ugi, I.; Dömling, A.; Hörl, W. Multicomponent Reactions in
Organic Chemistry. Endeavour 1994, 18, 115−122. (b) Tietze, L. F.
Domino Reactions in Organic Synthesis. Chem. Rev. 1996, 96, 115−
136.
(10) (a) Shen, Y.; Gu, Y.; Martin, R. sp3 C−H Arylation and
Alkylation Enabled by the Synergy of Triplet Excited Ketones and
Nickel Catalysts. J. Am. Chem. Soc. 2018, 140, 12200−12209. (b) Fan,
X.-Z.; Rong, J.-W.; Wu, H.-L.; Zhou, Q.; Deng, H.-P.; Tan, J. D.; Xue,
C.-W.; Wu, L.-Z.; Tao, H.-R.; Wu, J. Eosin Y as a Direct Hydrogen-
Atom Transfer Photocatalyst for the Functionalization of C−H
Bonds. Angew. Chem., Int. Ed. 2018, 57, 8514−8518. (c) Capaldo, L.;
Merli, D.; Fagnoni, M.; Ravelli, D. Visible Light Uranyl Photo-
catalysis: Direct C−H to C−C Bond Conversion. ACS Catal. 2019, 9,
3054−3058. (d) Perry, I. B.; Brewer, T. F.; Sarver, P. J.; Schultz, D.
M.; DiRocco, D. A.; MacMillan, D. W. C. Direct Arylation of Strong
Aliphatic C−H bonds. Nature 2018, 560, 70−75. (e) Tzirakis, M. D.;
Lykakis, I. N.; Orfanopoulos, M. Decatungstate as an Efficient
Photocatalyst in Organic Chemistry. Chem. Soc. Rev. 2009, 38, 2609−
2621. (f) Supranovich, V. I.; Levin, V. V.; Dilman, A. D. Radical
Addition to N-Tosylimines via C−H Activation Induced by
Decatungstate Photocatalyst. Org. Lett. 2019, 21, 4271−4274.
(g) Capaldo, L.; Ravelli, D. Hydrogen Atom Transfer (HAT): A
Versatile Strategy for Substrate Activation in Photocatalyzed Organic
Synthesis. Eur. J. Org. Chem. 2017, 2017, 2056−2071. (h) Capaldo,
L.; Quadri, L. L.; Ravelli, D. Photocatalytic hydrogen atom transfer:
the philosopher’s stone for late-stage functionalization? Green Chem.
2020, 22, 3376−3396.
(2) (a) Toure, B. B.; Hall, D. G. Natural Product Synthesis Using
Multicomponent Reaction Strategies. Chem. Rev. 2009, 109, 4439−
4486. (b) Rotstein, B. H.; Zaretsky, S.; Rai, V.; Yudin, A. K. Small
Heterocycles in Multicomponent Reactions. Chem. Rev. 2014, 114,
8323−8359. (c) Dömling, A.; Wang, W.; Wang, K. Chemistry and
Biology of Multicomponent Reactions. Chem. Rev. 2012, 112, 3083−
3135.
(3) Hummel, J. R.; Ellman, J. A. Convergent Synthesis of α-
Branched Amines by Transition-Metal-Catalyzed C−H Bond
Additions to Imines. Isr. J. Chem. 2017, 57, 916−931.
(4) (a) Abdel-Magid, A. F.; Mehrman, S. J. A Review on the Use of
Sodium Triacetoxyborohydride in the Reductive Amination of
Ketones and Aldehydes. Org. Process Res. Dev. 2006, 10, 971−1037.
(b) McGonagle, F. I.; MacMillan, D. S.; Murray, J.; Sneddon, H. F.;
Jamieson, C.; Watson, A. J. B. Development of a Solvent Selection
Guide for Aldehyde-Based Direct Reductive Amination Processes.
Green Chem. 2013, 15, 1159−1165.
(5) (a) Afanasyev, O. I.; Kuchuk, E.; Usanov, D. L.; Chusov, D.
Reductive Amination in the Synthesis of Pharmaceuticals. Chem. Rev.
2019, 119, 11857−11911. (b) Heinz, C.; Lutz, J. P.; Simmons, E. M.;
Miller, M. M.; Ewing, W. R.; Doyle, A. G. Ni-Catalyzed Carbon-
Carbon Bond-Forming Reductive Amination. J. Am. Chem. Soc. 2018,
140, 2292−2300.
(11) (a) Sridharan, V.; Suryavanshi, P. A.; Menendez, J. C. Advances
in the Chemistry of Tetrahydroquinolines. Chem. Rev. 2011, 111,
7157−7259. (b) Liu, D.; Zhao, G.; Xiang, L. Diverse Strategies for the
Synthesis of the Indoline Scaffold. Eur. J. Org. Chem. 2010, 2010,
3975−3984.
(6) (a) Yi, J.; Badir, S. O.; Alam, R.; Molander, G. A. Photoredox-
Catalyzed Multicomponent Petasis Reaction with Alkyltrifluorobo-
rates. Org. Lett. 2019, 21, 4853−4858. Also see selected examples of
alkylation reaction of imines: (b) Hatano, M.; Suzuki, S.; Ishihara, K.
Highly Efficient Alkylation to Ketones and Aldimines with Grignard
Reagents Catalyzed by Zinc(II) Chloride. J. Am. Chem. Soc. 2006,
128, 9998−9999. (c) Huang, J. M.; Wang, X. X.; Dong, Y.
Electrochemical Allylation Reactions of Simple Imines in Aqueous
(12) Cao, H.; Kuang, Y.; Shi, X.; Wong, K. L.; Tan, B. B.; Kwan, J.
M. C.; Liu, X.; Wu, J. Photoinduced Site-Selective Alkenylation of
Alkanes and Aldehydes with Aryl Alkenes. Nat. Commun. 2020, 11,
1956−1963.
(13) See the proposed mechanism in the Supporting Information.
4477
https://doi.org/10.1021/acs.orglett.1c01412
Org. Lett. 2021, 23, 4473−4477