Photoinduced Palladium-Catalyzed Carbofunctionalization of Conjugated Dienes Proceeding via Radical-Polar Crossover Scenario: 1,2-Aminoalkylation and beyond

Article abstract of DOI:10.1021/jacs.0c03993

A photoinduced palladium-catalyzed 1,2-carbofunctionalization of conjugated dienes has been developed. This mild modular approach, which does not require employment of exogeneous photosensitizers and external oxidants, allows for efficient and highly regio- and stereoselective synthesis of a broad range of allylic amines from readily available 1,3-dienes, alkyl iodides, and amines. Employment of O- and C-nucleophiles toward oxyalkylation and dialkylation products was also demonstrated. A putative π-allyl palladium radical-polar crossover path is proposed as a key event in this three-component coupling process. The utility of this protocol is highlighted by its application for derivatization of several amine-containing drugs.

Full text of DOI:10.1021/jacs.0c03993

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Communication
Photoinduced Palladium-Catalyzed Carbofunctionalization
of Conjugated Dienes Proceeding via Radical-Polar
Crossover Scenario: 1,2-Aminoalkylation and Beyond
Kelvin Pak Shing Cheung, Daria Kurandina, Tetsuji Yata, and Vladimir Gevorgyan
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 14 May 2020
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Journal of the American Chemical Society
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Photoinduced Palladium-Catalyzed Carbofunctionalization of
Conjugated Dienes Proceeding via Radical-Polar Crossover Scenar-
io: 1,2-Aminoalkylation and Beyond
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Kelvin Pak Shing Cheung, Daria Kurandina, Tetsuji Yata, and Vladimir Gevorgyan*
Department of Chemistry and Biochemistry, The University of Texas at Dallas, 800 West Campbell Road, Richardson, Texas 75080-
3021, United States
ABSTRACT: A photoinduced palladium-catalyzed 1,2-carbofunctionalization of conjugated dienes has been developed. This mild modular
approach, which does not require employment of exogeneous photosensitizers and external oxidants, allows for efficient and highly regio- and
stereoselective synthesis of a broad range of allylic amines from readily available 1,3-dienes, alkyl iodides, and amines. Employment of O- and
C-nucleophiles toward oxyalkylation and dialkylation products was also demonstrated. A putative p-allyl palladium radical-polar crossover
path is proposed as a key event in this three-component coupling process. The utility of this protocol is highlighted by its application for deri-
vatization of several amine-containing drugs.
3
Scheme 1. Background and Proposed 1,2-Carboamination of
1,3-Dienes
medicinal chemistry. Difunctionalization of 1,3-dienes enables
rapid access to complex molecules in one step and is therefore high-
4
ly sought after. In particular, 1,2-carboamination of dienes repre-
sents an efficient synthetic route to allylic amines, which are valua-
ble synthons, as well as important motifs in bioactive molecules
(Scheme 1a). However, only isolated examples have been reported
to date, with the vast majority being two-component annulative
reactions proceeding at elevated temperatures (Scheme 1b). As a
result, not only the choice of substrates but also the diversity of
obtained products is limited. A multicomponent reaction (MCR)
in which the carbon and nitrogen functionalities are introduced
independently would therefore be an appealing method to address
current limitations and allow for expedient synthesis of structurally
diverse allylic amines. Herein, we report a light-induced palladium-
catalyzed three-component coupling of 1,3-dienes, alkyl iodides
and amines that occurs under mild conditions. (Scheme 1c). This
transformation is proposed to involve a putative p-allyl hybrid pal-
ladium-radical intermediate A. The latter, upon radical-polar cross-
a Bioactive allylic amines
H
N
5
O
Me
F
F3C
F
NH
Me NH2
N
Ph
N
O
Me
H
DPC-082
6
Huperzine A
AChE inhibitor
Naftifine
Antifungal
Reverse transcriptase
inhibitor
O
CO2Et
i-Pr
N
O
O
O
NH
H
O
MeO
O
N
H
O
Me
OMe
N
O
O
O
OH
NH
Me
HO Me
Chronic myeloid leukaemia
F
7
Rupintrivir
HRV 3C protease inhibitor
Omacetaxine
b Annulative reactions
Dieck, Lꢀꢁꢂꢃꢄ, Overman, Lloyd-Jones & Booker-Milburn,
Yang, Chemler, Han, and Gong
over step is converted into a “traditional” p-allyl palladium inter-
R2N
R2HN
[Pd] or [Cu]
+
R1
8
mediate B, which is then trapped with amine to deliver the reac-
R1
heat
X
X = I, H or BF3K
tion products.
c This work: Intermolecular, multicomponent reaction
In recent years, the photoinduced palladium catalysis has be-
9
come a highly emerging area of research. It has been established by
Nu
[Pd]
R1
R3I
+
+
R3
NuH
R1
R2
blue LED
our group and others that hybrid palladium radical species can be
generated via cleavage of C(sp3)- and C(sp2)—X (X = Cl, Br, I,
CO2NPhth, OTf) bonds in the presence of photoexcited palladium
R2
Readily available
LnPdI
LnPdII
R3
R3
via
R1
R1
complexes. Formation of these species was crucial for achieving
R2
R2
10
A
π-allyl Pd radical-polar crossover
B
various processes, including remote desaturation, alkyl Heck reac-
11
12
tions , and other transformations. Keeping in mind a facile addi-
tion of hybrid alkyl radical palladium species across double bond,11
we envisioned that analogous addition at conjugated diene would
1,3-Dienes are readily available versatile building blocks, which
enjoy numerous applications in synthesis, material science, and
1
2
1
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Journal of the American Chemical Society
yields (8–12). Notably, in the case of phenol-containing moiety
Page 2 of 8
Table 1. Optimization of Reaction Conditionsa
1
(9), the formation of a potential competing carboalkoxylation
product was not observed, thus indicating high chemoselectivity of
this reaction. Electron-deficient aryl groups were also tolerated,
thus delivering the expected products in moderate to good yields
(13–15). Alkyne and halides functionalities were also compatible
with this transformation (16–19). Aminoalkylation of dienes pos-
sessing substituents at meta- and ortho- positions of the arene pro-
ceeded uneventfully producing the reaction products 20–24. Fer-
rocenyl and heteroaryl groups were also amenable to this catalytic
process, affording the corresponding products in moderate to good
yields (25–30). Alkyl-substituted dienes were also reactive under
these reaction conditions. Selective 1,2-addition was observed with
secondary alkyl substituent (31), whereas mixtures of 1,2- and 1,4-
adducts were isolated for the primary counterparts (32–33), prob-
ably due to steric reasons. In addition, this MCR can be performed
with trienes to obtain the corresponding dienamines 34–35. Lower
yield from diene ester (36) was obtained, presumably due to the
electronic mismatch between silylmethyl radical and electron-
deficient diene ester. Importantly, 1,2-disubstituted butadiene was
also proved to be viable substrate to produce trisubstituted alkenyl
amine 37. Higher catalyst loading, however, was required to
achieve reasonable yield for this substrate.
2
3
4
5
6
7
8
9
PdCl2 (5 mol%)
Xantphos (10 mol%)
AgNTf2 (10 mol%)
Cs2CO3 (1 equiv)
Me
Bn
N
Me
Bn
Me
Bn
H
N
N
+
3
THF (0.5 M)
rt, 15 h
blue LED
Ph
TMS Ph
TMS
I
TMS
2
Ph
(E)-1
4a
1,2-addition
4b
1,4-addition
standard conditions
Side products
Me
Bn
Bn
N
N
TMS
Ph
TMS
Me
Ph
Me
6
hydroamination
7
SN
5
Heck
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
2
Deviation from
standard condi-
tions
Entry
4:5:6:7b
Yield of 4ac
1
2
3
4
5
6
None
98:1:0.5:0.5
96:1:1:2
8:0:0:92
4:0:0:96
91:5:2:2
62:29:7:2
89% (80%)
83% (75%)
Trace
(E)/(Z)-1 (1:1.2)
45 or 80 oC (dark)
Without PdCl2
Without AgNTf2
Without Cs2CO3
Trace
48%d
44%
a 0.2 mmol scale; (E)-1:2:3 = 1:1.3:1.3. b Determined by GC/MS using
Next, the scope of alkyl iodides has been evaluated. Primary alkyl
c
1
pentadecane as internal standard; 4a:4b > 20:1. Determined by H
NMR using dibromomethane as internal standard; isolated yields given
in parentheses. d Formation of substantial amounts of radical dimeriza-
tion products was observed.
iodides bearing a-silyl or germyl substituents reacted efficiently to
furnish the coupling products 38–40 in reasonable to good yields.
Reactions employing primary alkyl iodides gave diminished yields
(41–44), presumably due to stronger C—I bond and thus lower
reactivity,11 b, as well as due to competing alkylation reaction of the
14
also be feasible, thereby leading to a putative hybrid p-allyl palladi-
um radical species A that would exist in equilibrium with the classi-
cal p-allyl complex B. The anticipated aminoalkylation product
would be delivered upon nucleophilic attack by amine at the latter
(Scheme 1c).
To this end, we commenced our study with examining the reac-
tion of 1-phenylbutadiene (1), (trimethylsilyl)methyl iodide (2)
and N-methylbenzylamine (3). Expectedly, the major challenge
was to suppress the expected side reactions, including Heck reac-
tion (5), hydroamination (6), and amine alkylation (7) processes.
amine. In contrast, different secondary alkyl iodides reacted well
producing the corresponding allylic amines 45–50 in good yields.
Due to the steric reasons, employment of bulky tert-butyl iodide,
however, produced nearly equimolar mixture of 1,2- and 1,4-
adducts (51). This reaction was found to be very general with the
respect to the secondary amine used. Thus, benzylamines readily
participated in this reaction, delivering the allylic amines 52–55 in
moderate to good yields. Amine containing a picolyl moiety (56)
was also found to be effective. Aliphatic acyclic amines also reacted,
though with somewhat lower efficiency (57–58). Reactions with
various amine heterocycles, including pyrrolidine, piperidine, pi-
perazine, and morpholine, proceeded smoothly to furnish the tar-
get allylic amines in good yields (59–64), presumably due to higher
13
After extensive screening of reaction parameters, we were delight-
ed to obtain 4a in 80% isolated yield (Table 1, entry 1). Similarly to
our previous studies,11a the combination of Pd salt with Xantphos
ligand proved to be the most efficient catalytic system. This reac-
tion appeared to be insensitive to the stereochemistry of diene, as
employment of a 1:1.2 mixture of (E)/(Z) isomers of 1 did not
lead to significant change of the yield (entry 2). Control experi-
ments indicated that both visible light irradiation and palladium
catalyst were necessary (entries 3, 4). Without silver triflimide (en-
try 5), the reaction was significantly less efficient due to the for-
mation of substantial amounts of radical dimerization products
(see Figure 4b and discussion, therein). Likewise, the reaction effi-
ciency was substantially lower in the absence of the base (entry 6).
Employment of bromo analog of 2 was much less efficient (24%),
whereas the chloro counterpart did not react under these condi-
tions at all.
15
nucleophilicity in comparison to that of their acylic counterparts.
Remarkably, reactions of less nucleophilic N-Me-aniline and indo-
line were successful, as well (65–66). Importantly, employment of
allylic amines led to the corresponding di- and triallylamines, albeit
in low yields (67–68). Notably, N-methyl-1-naphthyl amine un-
derwent smooth reaction to give 69, which represents an alkylated
analogue of the drug naftifine. The scope of this transformation was
also tested in a more complex setting. Hence, a secondary amine
moiety of ciprofloxacin and desloratadine drugs was successfully
converted into allylic amine functionality (70–71).
Importantly, 1,3-dienes containing substituents at C2 and/or C3
positions were also proven competent reaction partners. However,
in these cases, 1,4-aminoalkylation products 73 and 75 were ob-
16
With the optimized conditions in hand, we examined the gener-
ality of this methodology (Table 2). First, the diene scope was test-
ed. It was found that 1-aryl- and hetaryl substituted dienes are all
capable partners for this transformation. Thus, electron-rich dienes
reacted smoothly to give the corresponding allyic amines in good
tained selectively (Scheme 2).
Moreover, the use of O- and C-nucleophiles, such as phenol-
(76) and malonate derivatives (78), respectively, led to the 1,2-
carbofunctionalization products in reasonable yields (Scheme 3).
2
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Journal of the American Chemical Society
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Table 2. Scope of Three-Component 1,2-Carboamination of 1,3-Dienesa
PdCl2 (5 mol%)
Xantphos (10 mol%)
AgNTf2 (10 mol%)
Cs2CO3 (1 equiv)
R5
R4
R5
R4
R5
N
N
R4
R1
R3I
R3
R3
+
+
N
H
R1
R1
R2
THF (0.5 M)
rt, 15 h
blue LED
R2
R2
8
9
Diene scope
Bn
N
Me
Bn
Me
Bn
Me
Bn
Me
Bn
Me
Me
Bn
N
N
N
N
N
TMS
TMS
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
TMS
TMS
TMS
TMS
O
TMS
Me2N
F3C
Me
HO
MeO
8, 76%
9, 75%
10, 78%
11, 73%
12, 83%
13, 67%
Me
Bn
Me
Bn
Me
Bn
N
Me
N
Bn
Me
N
Bn
Me
N
Bn
N
N
TMS
TMS
TMS
TMS
TMS
MeO2C
NC
F
Cl
Br
TMS
14, 75%
15, 62%
16, 70%
17, 67%
18, 65%
19, 53%b,c
Me Bn
N
Me
N
Bn
Me
N
Bn
Me
N
Bn
Me
Bn
Me
Bn
Me
Me
N
Ph
N
TMS
Me
F
TMS
TMS
TMS
TMS
TMS
Fe
Me
Me
20, 68%
21, 76%
22, 66%
23, 59%
24, 52%
25, 60%
Me Bn
Me
Bn
Me
Bn
Me
N
Bn
Me
N
Bn
Me
N
Bn
N
N
N
TMS
TMS
TMS
TMS
TMS
TMS
N
MeN
BocN
S
N
26, 65%
27, 65%
Me Bn
28, 78%
29, 42%
30, 65%
31, 63%
Me Bn
Me
Bn
Me
N
Bn
Me
Bn
Me
Bn
N
N
N
N
N
EtO
TMS
Ph
TMS
TMS
Ph
TMS
TMS Ph
TMS
O
Me
37, 55%d
32, 62%
(1.4:1 r.r.)
33, 56%
(1.3:1 r.r.)
34, 66%
(1.4:1 r.r.)
35, 65%
36, 30%c
Halide scope
Me
Bn
Me
Bn
Me
Bn
N
Me
Bn
Me
Bn
Me
Bn
N
Me
Bn
N
N
N
N
N
Ph
n-Bu
t-Bu
Ph
i-Pr
Ph
SiMe2Ph Ph
SiMe2(Ot-Bu) Ph
39, 55%
GeMe3
Ph
t-Bu
Ph
38, 81%
Me Bn
40, 78%
Me Bn
41, 68%
Me Bn
42, 56%
Me Bn
43, 48%
44, 54%
Me Bn
Me
Bn
Me
Bn
N
N
TMS
N
N
N
N
O
NBoc
N
O
Ph
TMS
Ph
Ph
Ph
Ph
Ph
Ph
45, 32%
(2:1 r.r.)
46, 70%
47, 70%
(13:1 r.r.)
48, 67%
49, 76%
50, 80%
51, 46%
(1:1.2 r.r.)
Amine scope
N
F
Me
PMB
Me
Bn
Bn
Me
Et
Et
Me
i-Pr
N
N
N
N
N
N
N
Ph
TMS
Ph
TMS
Ph
TMS
Ph
TMS
Ph
TMS
Ph
TMS
Ph
TMS
52, 70%
53, 65%
54, 71%
55, 68%
56, 59%
57, 59%
58, 38%
Me
Me
N
Ph
N
O
N
Me
Ph
N
N
N
N
N
N
Ph
TMS
Ph
TMS
Ph
TMS
Ph
TMS
Ph
TMS
Ph
TMS
Ph
TMS
59, 47%
60, 70%
(4:1 r.r.)
61, 68%
(4:1 r.r.)
62, 71%
63, 75%
64, 60%
65, 65%c,e
Drug analogue & derivatives
OMe
O
O
N
F
Me
N
N
N
N
TMS
Me
N
Ph
TMS
Ph
TMS
Ph
TMS
TMS
N
66, 83%
67, 25%
68, 26%
N
Ph
TMS
N
Cl
70, 58%f
from ciprofloxacin
methyl ester
71, 75%g
from desloratidine
69, 81%
naftifine analogue
Ph
Ph
a 0.4 mmol scale; isolated yields. b NMR yield. c 0.2 mmol scale. 10 mol% PdCl2, 20 mol% Xantphos and 20 mol% AgNTf2 were used. e 10 mol%
d
Pd(OAc)2, 20 mol% Xantphos and 20 mol% AgNTf2 were used. f THF/MeOH = 1:1 (0.25 M). g THF/DCM = 2:1 (0.33 M).
3
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Based on the results of the aforementioned studies, the following
Page 4 of 8
Scheme 2. Examples of 1,4-Carboamination of 1,3-Dienesa
1
2
3
4
reaction mechanism is proposed (Scheme 5). First, photoexcited
Me
Me
standard conditions
Bn
Me
Bn
+
+
N
H
TMS
I
N
TMS
Scheme 4. Mechanistic Studies
Me
72
Me Me
73, 73%
2
3
a Reaction in the presence of TEMPO
5
6
7
8
TEMPO (2 equiv)
PdCl2 (10 mol%)
Xantphos (20 mol%)
AgNTf2 (20 mol%)
Cs2CO3 (1 equiv)
Ph
Ph
Me
Bn standard conditions
Bn
+
+
N
TMS
I
N
TMS
Me
Bn
H
Me
Me
N
Me
Me
Bn
75, 59%
74
2
3
H
N
+
3
N
a 0.4 mmol scale; isolated yields.
O
TMS
THF (0.5 M)
rt, 12 h
blue LED
I
TMS
2
Ph
TMS
Ph
Me Me
(E)-1
4a
0%
80
9
22% NMR yield
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 3. Employment of O- and C-Nucleophilesa
b Reaction without AgNTf2
Pd(OAc)2 (10 mol%)
Xantphos (20 mol%)
AgNTf2 (20 mol%)
no AgNTf2
PdCl2 (5 mol%)
Xantphos (10 mol%)
Cs2CO3 (1 equiv)
Me
Me
Bn
N
H
Me
Me
Bn
Ph
TMS
TMS
Cs2CO3 (1 equiv)
N
+
+
I
+
TMS
Ph
3
O
THF (0.5 M)
rt, 15 h
blue LED
THF (0.5 M)
rt, 12 h
blue LED
HO
Ph
TMS Ph
I
TMS
2
Ph
(E)-1
Ph
TMS
2
76
+ isomers
(E)-1
4a
77, 68%
44% NMR yield
81, 34%
Pd(OAc)2 (10 mol%)
Xantphos (20 mol%)
AgNTf2 (20 mol%)
Cs2CO3 (1 equiv)
c Reactions of π-allyl Pd complexes with TEMPO
O
O
O
O
Me Me
+
+
I
EtO
Ph
OEt
TMS
TMS
Ph
EtO
OEt
THF (0.5 M)
rt, 15 h
blue LED
Me Me
(E)-1
TEMPO (1.5 equiv)
2
78
Ph
O
N
O
79, 62%
X
Ph
Ph
P
Ph
CDCl3
Me
Me
P
Pd
Ph
Ph
82, X = I
83, X = NTf2
84
a 0.2 mmol scale; isolated yields.
complex
conditions
NMR yield of 84
rt, 0.5 h, blue LED
40 oC, 12 h, dark
74%
50%
82
83
rt, 0.5 h, blue LED
40 oC, 12 h, dark
59%
0%
Naturally, we were eager to elucidate the mechanism of this nov-
el transformation. We believe that under these reaction conditions,
an interplay between hybrid radical and ionic palladium intermedi-
ates takes place. The involvement of radical intermediates was un-
ambiguously supported by the following experiments. Thus, initial-
ly formed alkyl radicals from alkyl iodide 2 were trapped by 2,2,6,6-
tetramethylpiperidine-N-oxyl radical (TEMPO) in 22% yield
(Scheme 4a, 8011a). Next, the intermediacy of the allylic radicals
was uncovered in the reaction performed without silver triflimide.
In that case, the reaction produced a substantial amount of allylic
LnPd0 undergoes a single electron transfer (SET) process with alkyl
iodide to produce hybrid alkyl palladium radical species C,11 which
adds to the terminal position of diene to produce radical species A
that exists in equilibrium with p-allyl complex B. In the presence of
triflimide anion, this equilibrium is shifted towards complex B. A
subsequent attack of the amine at the latter delivers the carbofunc-
22
tionalization product and regenerates the palladium catalyst.
17
Scheme 5. Proposed Mechanism
radical dimerization products 81 (Scheme 4b, Table 1, entry 5).
Beneficial effect of accessing more electrophilic p-allyl palladium
Nu
base HX
R3I
LnPd0
R3
entities in reactions with nucleophiles by employing weakly-
R1
blue light
18
R2
coordinating anions is well documented. Accordingly, we pre-
sumed that employment of triflimide would not only render Pd-
complex more electrophilic, but would also potentially shift the
LnPdIX
R3
NuH, base
LnPdIIX
C
proposed equilibrium between p-allyl radical- and p-allyl ionic Pd
entities to the right (cf. Scheme 1c, A D B). To validate this as-
sumption, we synthesized model p-allyl palladium complexes bear-
R1
R3
R2
R1
R2
LnPdIX
B
19
R3
ing Xantphos ligand with iodide (82) and triflimide (83) counter-
R1
R2
A
ions and subjected them to the reaction with TEMPO under blue
20
light-irradiation (Scheme 4c). In both cases, the product of allyl
radical trapping (84)17c, was observed in good yields; however,
21
the reaction of 83 occurred at a slower rate as compared to that of
complex 82.13 Control experiments under the thermal conditions
showed that the reaction of 82 with TEMPO still proceeded albeit
much slower, while complex 83 was completely non-reactive under
such conditions. These results support our hypothesis that triflim-
ide anion stabilizes the p-allyl Pd complex against homolysis upon
irradiation with blue light or thermal conditions, thereby suppress-
ing the undesired radical dimerization process.
In conclusion, the first visible light-induced protocol for the in-
termolecular aminoalkylation, oxyalkylation and dialkylation of 1,3-
dienes has been developed. This mild multicomponent coupling
reaction, which utilizes readily available reaction partners with
broad functional group compatibility, does not require employ-
ment of exogeneous photosensitizers or external oxidants. It can be
used for the late-stage derivatization of complex molecules and
drugs. Preliminary mechanistic studies suggest that the radical-
polar crossover path is crucial for the success of this reaction. It is
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of densely functionalized alkenes will find use organic synthesis and
in drug discovery.
1,3-Dienes: From Racemic to Enantioselective. Synthesis 2019, 51, 122–
134.
(5) Skoda, E. M.; Davis, G. C.; Wipf, P. Allylic Amines as Key Building
Blocks in the Synthesis of (E)-Alkene Peptide Isosteres. Org. ProcessRes.
Dev. 2012, 16, 26–34.
Supporting Information
The Supporting Information is available free of charge at
Experimental procedures; analytical data for all new compounds
(PDF)
(6) (a) O’Connor, J. M.; Stallman, B. J.; Clark, W. G.; Shu, A. Y. L.;
Spada, R. E.; Stevenson, T. M.; Dieck, H. A. Some Aspects of Palladium-
Catalyzed Reactions of Aryl and Vinylic Halides with Conjugated Dienes in
the Presence of Mild Nucleophiles. J. Org. Chem. 1983, 48, 807–809. (b)
Larock, R. C.; Berrios-Peña, N.; Narayanan, K. Palladium-Catalyzed Het-
eroannulation of 1,3-Dienes by Functionally Substituted Aryl Halides. J.
Org. Chem. 1990, 55, 3447–3450. (c) Overman, L. E.; Rosen, M. D. Total
Synthesis of (–)-Spirotryprostatin B and Three Stereoisomers. Angew.
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Ford, J. G.; Gagné, M. R.; Lloyd-Jones, G. C.; Booker-Milburn, K. I. Dis-
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Carboamination of Dienes. J. Am. Chem. Soc. 2008, 130, 10066–10067. (e)
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2518. (g) Chen, S.-S.; Meng, J.; Li, Y.-H.; Han, Z.-Y. Palladium-Catalyzed
Enantioselective Heteroannulation of 1,3-Dienes by Functionally Substi-
tuted Aryl Iodides. J. Org. Chem. 2016, 81, 9402–9408. (h) Chen, S.-S.;
Wu, M.-S.; Han, Z.-Y. Palladium-Catalyzed Cascade sp2 C—H Functional-
ization/Intramolecular Asymmetric Allylation: From Aryl Ureas and 1,3-
Dienes to Chiral Indolines. Angew. Chem. Int. Ed. 2017, 56, 6641–6645. (i)
Zhang, T.; Shen, H.-C.; Xu, J.-C.; Fan, T.; Han, Z.-Y.; Gong, L.-Z. Pd(II)-
Catalyzed Asymmetric Oxidative Annulation of N-Alkoxyheteroaryl Am-
ides and 1,3-Dienes. Org. Lett. 2019, 21, 2048–2051. For an example of
non-annulative aminomethylamination reaction, see: (j) Liu, Y.; Xie, Y.;
Wang, H.; Huang, H. Enantioselective Aminomethylamination of Conju-
gated Dienes with Aminals Enabled by Chiral Palladium Complex-
Catalyzed C—N Bond Activation. J. Am. Chem. Soc. 2016, 138, 4314–
4317. (k) When this manuscript was under original submission, a related
work on light-induced two-component aminoalkylation of dienes has been
published: Huang, H.-M.; Koy, M.; Serrano, E.; Pflüger, P. M.; Schwarz, J.
L.; Glorius, F. Catalytic Radical Generation of π-Allylpalladium Complex-
es. Nat. Catal. 2020, 3, 393–400.
AUTHOR INFORMATION
Corresponding Author
Vladimir Gevorgyan – Department of Chemistry and Biochemistry,
University of Texas at Dallas, Richardson, Texas 75080, United States;
orcid.org/0000-0002-7836-7596; Email: vlad@utdallas.edu
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Authors
Kelvin Pak Shing Cheung – Department of Chemistry and
Biochemistry, University of Texas at Dallas, Richardson, Texas 75080,
United States
Daria Kurandina – Department of Chemistry and Biochemistry,
University of Texas at Dallas, Richardson, Texas 75080, United States
Tetsuji Yata – Department of Chemistry and Biochemistry, University of
Texas at Dallas, Richardson, Texas 75080, United States
Complete contact information is available at:
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank the National Institutes of Health (GM120281), National
Science Foundation (CHE-1936422), and Welch Foundation (Chair,
AT-0041) for financial support.
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É
Re
́
́
́
́s
en Pre
́
̀
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(22) Although, generation of alkyl radicals by light irradiation of EDA
complexes of alkyl halides with amines is known, the possibility of such
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ble 1, entry 4). For light-induced radical generation from EDA complexes,
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Promoted Photoactivation of Perfluoroalkyl Iodides: A Photochemical
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(c) Tang, X.; Studer, A. Alkene 1,2-Difunctionalization by Radical Alkenyl
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nation. Chem. Sci. 2019, 10, 9374–9379.
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TOC GRAPHICS
Nu
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[Pd]
R1
R3I
NuH
+
+
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R1
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blue LED
R2
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> 60 examples
R3
LnPdI
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LnPdII
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via
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π-allyl Pd radical polar crossover
• Modular synthesis • Broad scope
• Stereoconvergent
• Regioselective
• Exogeneous photosensitizer-free
• Mild conditions
• Redox neutral
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