Photoinduced Formation of Hybrid Aryl Pd-Radical Species Capable of 1,5-HAT: Selective Catalytic Oxidation of Silyl Ethers into Silyl Enol Ethers

Article abstract of DOI:10.1021/jacs.6b01628

A direct visible light-induced generation of a hybrid aryl Pd-radical species from aryl iodide and Pd(0) is reported to enable an unprecedented (for hybrid Pd-radical species) hydrogen atom-transfer event. This approach allowed for efficient desaturation of readily available silyl ethers into synthetically valuable silyl enols. Moreover, this oxidation reaction proceeds at room temperature without the aid of exogenous photosensitizers or oxidants.

Full text of DOI:10.1021/jacs.6b01628

Subscriber access provided by UOW Library
Communication
Photoinduced Formation of Hybrid Aryl Pd-Radical Species Capable of
1,5-HAT: Selective Catalytic Oxidation of Silyl Ethers into Silyl Enol Ethers
Marvin Parasram, Padon Chuentragool, Dhruba Sarkar, and Vladimir Gevorgyan
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.6b01628 • Publication Date (Web): 05 May 2016
Downloaded from http://pubs.acs.org on May 7, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of the American Chemical Society is published by the American Chemical
Society. 1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 5
Journal of the American Chemical Society
1
2
3
4
5
Photoinduced Formation of Hybrid Aryl Pd-Radical Species
Capable of 1,5-HAT: Selective Catalytic Oxidation of Silyl
Ethers into Silyl Enol Ethers
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
†
†
Marvin Parasram, Padon Chuentragool, Dhruba Sarkar, and Vladimir Gevorgyan*
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607-7061, United States
Supporting Information Placeholder
Pd(0); (2) capability of the formed hybrid aryl Pd-radical
species to undergo a 1,5-hydrogen atom transfer (HAT)
process (iii); (3) a new method for general, efficient, and
mild desaturation of silyl ethers (1) into silyl enol ethers (2)
(Scheme 1, b).
ABSTRACT: A direct visible light-induced generation of a
hybrid aryl Pd-radical species from aryl iodide and Pd(0) is
reported to enable an unprecedented (for hybrid Pd-radical
species) hydrogen atom transfer (HAT) event. This ap-
proach allowed for efficient desaturation of readily available
silyl ethers into synthetically valuable silyl enols. Moreover,
this oxidation reaction proceeds at room temperature with-
out the aid of exogenous photosensitizers or oxidants.
In his pioneering work, Curran reported a remote C–H
functionalization of alcohols via a 1,5-HAT processes utiliz-
ing a halo-aryl silane tether (1’) (eq 1).3a Standard radical
initiation of 1’ led to the aryl radical iii, which underwent 1,5-
HAT to produce alkyl radical iv capable of undergoing fur-
Aryl halides are vital starting materials for a variety of im-
portant Pd(0)-catalyzed C–C and C–heteroatom bond
forming reactions, which usually involve Pd(II) intermedi-
ates A, formed via a two-electron oxidative addition process
(Scheme 1, a).1 Alternatively, if a hybrid aryl Pd-radical spe-
cies B, possessing both traditional Pd and radical nature can
be realized, it may exhibit novel reactivity.2 Thus, if condi-
tions for a direct conversion of easily available aryl halides
into B will be found, it could trigger the development of an
array of novel transformations. The work described herein
features: (1) the first direct visible light-induced generation
of a hybrid aryl Pd-radical species (i) from aryl iodide and
3
ther useful free radical reactions. We thought of developing
an oxidative hybrid Pd-radical version of Curran’s free radical
chemistry as a potentially useful new method. Indeed, if a
hybrid aryl Pd-radical complex i, capable of HAT and a sub-
sequent β-hydride elimination could be generated (Scheme
1b), it would allow for a direct oxidation of silyl ethers (1)
into silyl enols (2).4,5 Clearly, the success of this process
hinges on the efficient generation of the hybrid aryl Pd-
radical species (i) from aryl halides, and capability of the
latter to undergo HAT, both of which, to the best of our
knowledge, are unprecedented.6,7 We envisioned that puta-
6,8
tive species i could possibly be generated either via thermal
or photochemical9,10 activation of an aryl iodide in the pres-
Scheme 1. Traditional and Proposed Novel Reactivity of
Aryl Halides in Pd(0)-Catalyzed Reactions
ence of Pd(0) complex.
Curran, 1988
Proposed Novel Reactivity
Traditional Reactivity
Pd(II)X
O
R
O
R
O
R
Pd(I)X
Me2Si
Me2Si
Me2Si
X
Cross-
Pd(0)
Pd(0)
Hybrid
Pd-Radical
Reactions
AIBN
X
H
H
H
1,5 HAT
(a)
Coupling
Reactions
Free Radical
Reactions
(1)
Bu3SnH
Δ
B
A
X = Hal
1'
iv
iii
This work
Novel Reactivity: Generation of Hybrid Aryl Pd-Radical Species Capable of 1,5 HAT
To this end, we first tested silyl-tethered alcohol 1a under
various thermal Pd-catalyzed conditions that have been de-
veloped for hybrid Pd-radical reactions of alkyl halides (Ta-
Pd(I)I
Pd(0)
1,5 HAT
H
H
H
H
H
(b)
O
O
O
2,6,11
O
Si
Si
ble 1).
However, employment of Pd(PPh3)4 or
Blue LED
room temp
Si
Si
H
H
Pd(I)I
PEPPSITM-IPr complexes resulted in hydro-dehalogenation12
of 1a (entries 1, 2). The combination of Pd(OAc)2 and bi-
dentate ferrocene ligands were also incompetent (entries 3,
4). Evidently, other means of activation were needed to
stimulate this process. We were intrigued by recent reports of
beneficial effect of visible light on promoting radical-type
transition metal-catalyzed transformations.9
I
no exogenous
photosensitizers
or oxidants!
i
ii
2
1
Known This Work
• Direct generation of hybrid
aryl Pd-radical species
from Ar-I and Pd(0)
• Hybrid Pd-radical species
involved in HAT process
• General, efficent, and mild
desaturation of silyl ethers
into silyl enol ethers
ACS Paragon Plus Environment

Journal of the American Chemical Society
Table 1. Optimization of the Reaction Conditions
Page 2 of 5
Table 2. Photoinduced Pd-Cat. Oxidation of Silyl Ethersa
1
2
3
4
5
6
7
8
9
PPh2
I
SiEt2
R3
PPh2
Catalyst (10 mol%)
Ligand (20 mol%)
I
Pd(OAc)2 (10 mol%)
L (20 mol%)
H
OSiEt2Ph
R3
Fe
O
Fe
O
O
Si
Cs2CO3 (2 equiv)
PhH, 12 h
R1
H
P(tBu)2
Si
R2
P(tBu)2
Cs2CO3 (2 equiv)
PhH, Blue LED, rt
R2
R1
R2
L
R = Et 1a
L
R2
2a
2
1
entry
Catalyst
Pd(PPh3)4
PEPPSITM-IPr
Pd(OAc)2
Pd(OAc)2
Pd(PPh3)4
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
-
Ligand
Conditions
120 oC
Yield, %a
0b
0b,c
OSiEt2Ph
OSiEt2Ph
OSiEt2Ph
OSiEt2Ph
1
2
3
4
5
6
7
8
9
-
-
dppf
L
120 oC
120 oC
0b
0b
O
R
2c, 86%
2e, 74%
2a, R = H, 79%
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
2d, 72%b
120 oC
2b, R = t-Bu, 64%
OSiEt2Ph
-
rt, Blue LED
rt, Blue LED
rt, Blue LED
rt, 23W CFL
rt, Blue LED
72
OSiEt2Ph
OSiEt2Ph
OSiEt2Ph
dppf
L
67
N
79 (79)d
49e
O
Boc
2i, 70%
2h, 65%
2f, 75%
L
2g, 58%
OSiEt2Ph
L
NR
o
OSiEt2Ph
OSiEt2Ph
OSiEt2Ph
Standard Conditions: 1a 0.05 mmol scale, PhH 0.1 M, 120 C or
a
b
34W Blue LED. NMR Yield. 14-35% of hydro-dehalogenation of
2k, 43%
1a was obtained. 5 mol% of catalyst was used. Isolated yield. e51%
c
d
2l, 61%
2m, 72%
2j, 58%
OSiEt2Ph
conversion of 1a.
OSiEt2Ph
OSiEt2Ph
R
R
Thus, we examined the reaction under irradiation of visible
light (Blue LED). Excitingly, product 2a was obtained in 72%
using Pd(PPh3)4 catalyst at room temperature (Table 1, entry
5). Remarkably, the reaction proceeded quite efficiently without
the use of any exogenous photosensitizers.13 Next, bidentate
phosphine ligand dppf with Pd(OAc)2 was tried, although, it
was less efficient (entry 6). Delightfully, 1-
diphenylphosphino-1′-(di-tert-butylphosphino)ferrocene
(L) was found to be the best ligand, producing desaturated
product 2a in 79% yield (entry 7). Notably, performing the
reaction with a 23W CFL led to lower efficiency (entry 8). A
control experiment indicated that the Pd-catalyst is crucial
for this reaction (entry 9). It was also found that both dime-
thyl- and diisopropyl substituted substrates were less effi-
cient.14 Obviously, this novel desaturation protocol requires
no external oxidants, which makes it milder compared to
other desaturation methods.4b,c,15
OSiEt2Ph
2q, R = F , 72%
2r, R = Cl, 85%
2n, R = Me, 79%
2o, R = t-Bu, 95%c
2p, R = TMS, 97%
2s, R = CN, 50%
2y, 61%e
OSiEt2Ph
2x, 79%
2t, R = H, 64%
2u, R = Me, 45%d
2v, R = OMe, 52%d
2w, R = CH(OH)CH3, 69%
O
H
H
OSiEt2Ph
OSiEt2Ph
H
H
H
PhEt2SiO
PhEt2SiO
2z, 58%f
2aa, 40% (95%)g
2ab, 58%
2ac, 75%
Standard Conditions: 1 0.2 mmol, Pd(OAc)2 0.02 mmol, L 0.04
a
mmol, Cs2CO3 0.4 mmol, PhH 0.1 M, 34W Blue LED, rt. Isolated
yields. b10:1 ratio, major isomer shown. c3 mmol scale = 99% isolat-
d
e
f
ed yield. Yield based on NMR ratios. Z:E = 3:1. Z:E:terminal =
7:3:1. Yield based on isolation of desilylated product, Camphor
(55% isolated yield).
g
possessing bulky groups at the β-position, such as -t-Bu (1o)
and -TMS (1p), provided 2o and 2p in 95% and 97% yields,
respectively. The practicality of this method was supported
by a scale-up experiment with 1.2 grams of 1o, where the
oxidation product 2o was produced in nearly quantitative
yield. Desaturation of 4-substituted benzylic alcohol deriva-
tives 1q-w containing different functionalities, including aryl
chloride (1r), cyanide (1s) and unprotected 2oalcohol (1w),
proceeded well, producing moderate to good yields of the
corresponding silyl enol ethers. Moreover, a double-fold
desaturation of diol derivative 1x led to the dienol ether 2x in
good yield. This methodology also has proven to be efficient
on challenging linear substrates, which are known to be unse-
lective in HAT protocols.3a,3d,17 Thus, 4-heptanol 1y and 2-
hexanol 1z, selectively generated their respective α-β desatu-
rated products (2y, z) in good yields, although as a mixture
of stereoisomers.18 Then, we investigated our technology
towards functionalization of more complex molecules. Thus,
With the optimized conditions in hand, the generality of
this reaction was examined. Thus, cyclohexanol derivatives
(1b-d) reacted smoothly to produce silyl enol ethers 2b-d in
good
yields.
Heterocycles,
possessing
4-
hydroxyltetrahydropyran (1e), 4-chromanol (1f), and 4-
hydroxylpiperidine (1g) motifs, afforded products 2e-g in
good yields. Cyclopentanol derivatives 1h-j were found to
produce 2h-j in reasonable yields. Moreover, cyclobutanol
(1k) and medium sized cyclic-alcohol derivatives (1l-m)
were found to be competent substrates as well, producing the
corresponding products 2k-m in moderate to good yields.
Next, we tested this methodology on desaturation of acyclic
ethers, which are known to react inefficiently in dehydro-
genation reactions.16 Hence, desaturation of 2-propanol de-
rivative1n produced 2n efficiently. Likewise, substrates
2
ACS Paragon Plus Environment

Page 3 of 5
Journal of the American Chemical Society
terpenes 1aa and 1ab reacted well, though the former pro- Scheme 2. Possible Mechanisms
1
2
3
4
5
6
7
8
duced an unstable silyl enol (2aa) that resulted in 40% iso-
lated yield along with 55% yield of desilylated ketone prod-
uct (Camphor). Oxidation of steroid androstanone 1ac,
bearing multiple sites of desaturation, proceeded smoothly,
producing 2ac in 75% yield as a sole regioisomer.
ation
Oxid
A3
Hα
Si O
Hβ
8
Hβ
Hα
O
Si
A1
Direct
H-elimination
A2
Pd(I)I
Recom-
bination
6
Hα
sfer
Tran
A4
Atom
Pd(II)I
1,5-HAT
Si
O
Hβ
We foresee two distinct mechanistic scenarios for this nov-
el oxidation reaction, a radical pathway (Path A) and a con-
certed metalation deprotonation (CMD) protocol (Path B)
Hα
7
Hβ
O
Si
β–H
elimination
9
I
Pd(I)I
O
Hα
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Hα
Si
(Scheme 2). First, under visible light (Blue LED), a direct
3
Path A
O
Hβ
Si
Hybrid Aryl Pd-Radical
(1,5-HAT)
2,6,10,11
SET
from excited Pd(0) complex to aryl iodide 1a pro-
2a
HβPd(II)I
SET
via
duces a hybrid Pd-radical intermediate 3 (Path A). In an
-
1a
19
B
*
alternative, though, less likely scenario, the latter can form
Pd(II)I
B
HβI
*
O
through a conventional oxidative addition of Pd(0) complex
to 1a to form the Pd(II) intermediate 4, followed by its exci-
tation into 520 and a subsequent homolysis.21 Then, 3 under-
goes a 1,5-HAT of Hα to generate the hybrid alkyl Pd-radical
complex 6, which subsequently produces silyl enol 2a either
via recombination and successive β-hydride elimination of
LnPd(0)
1a
Si
Hα
Hβ
Hβ
5
O
Si
2a'
Si
Pd(II)I
O
4
Hα
Hβ
Pd(II)Hβ
O
Path B
Si
Concerted
Metalation-Deprotonation
(CMD)
12
O
11
Hβ (Path A1), or via a direct Hβ–atom elimination22 with
O
O
Pd(I)I (Path A2). Potentially, 6 can also be converted to 2a
either via oxidation by Pd(I)I into a cationic intermediate 8,
Pd(II) Hα
Si
O
I
Hβ
Pd(II)
Hβ
followed by its deprotonation (Path A3), or via an atom
10
O
Si
23,24
Si
O
Hα
transfer/HI-elimination sequence (Path A4).
In the al-
Et2
CMD
Hβ
11
ternative pathway (Path B), intermediate 4 undergoes a
1a
-
HαCO3
16a,25
CMD process
of Hα (410) to produce palladacycle 11.
The following β-hydride (Hβ) elimination of the latter occurs
to generate the aryl Pd(II) silyl enol intermediate 12. A sub-
sequent reductive elimination yields 2a’ and regenerates the
Pd(0) catalyst. However, the performed deuterium-labeling
experiments disproved this mechanism (Path B).14
Scheme 3. Radical Clock Experiment
I
Et2Si
Pd(OAc)2 (10 mol%)
Et2Si
Et2Si
Et2Si
L (20 mol%)
O
Me
O
Me
O
O
Me
Ph
Cs2CO3 (2 equiv)
C6D6, Blue LED,
12 h, rt
Ph
Ph
Ph
13
The intermediacy of radical species (Path A) was support-
14
not observed
15
16
11
78% (NMR)
Trans : Cis = 2.1 : 1
not observed
ed by the use of radical scavengers and radical clock exper-
iments.14,26 Hence, it was found that employment of radical
traps, such as galvinyloxy and TEMPO, completely sup-
pressed the reaction.14 It was also found that cyclopropyl-
containing substrate 13 under standard reaction conditions
underwent smooth ring opening of the cyclopropyl ring pro-
ducing 16 as the major product (Scheme 3). Notably, for-
mation of product 14 with preserved cyclopropyl unit and
ASSOCIATED CONTENT
Experimental procedures and compound characterization data.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
27
the β–C elimination product 15 were not detected.
Corresponding Author
vlad@uic.edu
In conclusion, we demonstrated the first direct generation
of a hybrid aryl Pd-radical species from aryl halides and
Pd(0), and its capability of promoting 1,5-HAT process,
which allowed for a general mild and efficient conversion of
easily available silyl ethers into valuable silyl enol ethers.
Notably, this photoinduced Pd-catalyzed reaction proceeds
at room temperature without any exogenous photosensitiz-
ers or oxidants. We envision that this methodology can be
applied for a late-stage desaturation of complex molecules.
Author Contributions
†M.P. and P.C. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We thank National Science Foundation (CHE-1362541) for
financial support of this work.
3
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 5
REFERENCES
1
2
3
4
5
6
7
8
9
(11) (a) Bloome, K. S.; McMahen, R. L.; Alexanian, E. J. J. Am. Chem.
Soc. 2011, 133, 20146. (b) Parasram, M.; Iaroshenko, V. O.; Gevorgyan, V.
J. Am. Chem. Soc. 2014, 136, 17926. (c) Bonney, K. J.; Proutiere, F.;
Schoenebeck, F. Chem. Sci. 2013, 4, 4434.
(12) Hydro-dehalogenation of the reactants is the common side process
Pd-catalyzed and radical type reactions, see, for example references 11
and 3.
(13) For recent reviews on visible light photocatalytic reactions employ-
ing exogenous photosensitizers, see: (a) Prier, C. K.; Rankic, D. A.; Mac-
Millan, D. W. C. Chem. Rev. 2013, 113, 5322. (b) Xi, Y.; Yi, H.; Lei, A. Org.
Biomol. Chem. 2013, 11, 2387. (c) Reckenthaler, M.; Griesbeck, A. G. Adv.
Synth. Catal. 2013, 355, 2727. (d) Jeffrey, J. L.; Terrett, J. A.; MacMillan, D.
W. C. Science 2015, 349, 1532. For aryl radicals species in visible light pho-
toinduced reactions with photosensitizers, see: Kalyani, D.; McMurtrey, K.
B.; Neufeldt, S. R.; Sanford, M. S. J. Am. Chem. Soc. 2011, 133, 18566.
(14) See SI for details.
(15) (a) Diao, T.; Stahl, S. S. J. Am. Chem. Soc. 2011, 133, 14566. (b)
Nicolaou, K. C.; Gray, D. L. F.; Montagnon, T.; Harrison, S. T. Angew.
Chem., Int. Ed. 2002, 41, 996. (c) Uyanik, M.; Akakura, M.; Ishihara, K. J.
Am. Chem. Soc. 2009, 131, 251.
(16) (a) Yao, W.; Zhang, Y.; Jia, X.; Huang, Z. Angew. Chem., Int. Ed.
2014, 53, 1390. (b) Lyons, T.W.; Bezier, D.; Brookhart, M. Organometal-
lics. 2015, 34, 4058.
(17) Curran, D. P.; Xu, J. J. Am. Chem. Soc. 1996, 118, 3142.
(18) Tsunoi, S.; Ryu, I.; Okuda, T.; Tanaka, M.; Komatsu, M.; Sonoda,
N. J. Am. Chem. Soc. 1998, 120, 8692.
(19) Attempts to isolate intermediate complex 4 via reaction of Pd(0)
complexes with 1a failed, presumably due to steric hindrance of bulky silyl
tether. Therefore, the SET path is considered as more likely. See SI for
details.
(20) For examples utilizing photoinduced Pd(II) excited complexes,
see: (a) To, W.-P.; Liu, Y.; Lau, T.-C.; Che, C.-M. Chem. Eur. J. 2013, 19,
5654. (b) Ozawa, F.; Yamamoto, A.; Ikariya, T.; Grubbs, R. H. Organome-
tallics 1982, 1, 1481. (c) Wakatsuki, Y.; Yamazaki, H.; Grutsch, P. A.; San-
thanam, M.; Kutal, C. J. Am. Chem. Soc. 1985, 107, 8153.
(21) For examples of generating radical species from Pd(II) complexes,
see: (a) Kraatz, H.-B.; van der Boom, M. E.; Ben-David, Y.; Milstein, D. Isr.
J. Chem. 2001, 41, 163. (b) Seligson, A. L.; Trogler, W. C. J. Am. Chem. Soc.
1992, 114, 7085. (c) Lanci, M. P.; Remy, M. S.; Kaminsky, W.; Mayer, J.
M.; Sanford, M. S. J. Am. Chem. Soc. 2009, 131, 15618.
(22) (a) Kuo, J. L.; Hartung, J.; Han, A.; Norton, J. R. J. Am. Chem. Soc.
2015, 137, 1036. (b) Hu, Y.; Shaw, A. P.; Estes, D. P.; Norton, J. R. Chem.
Rev. 2016, DOI: 10.1021/acs.chemrev.5b00532.
(23) However, an attempt to detect intermediate 9 in stoichiometric
NMR experiment failed. See SI for details.
(24) Alternative hypothetical scenarios may include radical chain mech-
anism (see ref. 6), or electron catalysis mechanism. See, Studer, A.; Curran,
D. P. Nat. Chem. 2014, 6, 765.
(25) (a) Kefalidis, C. E.; Davi, M.; Holstein, P. M.; Clot, E.; Baudoin, O.
J. Org. Chem. 2014, 79, 1190. (b) Baudoin, O.; Herrbach, A.; Gueritte, F.
Angew. Chem., Int. Ed. 2003, 42, 5736. (c) Motti, E.; Catellani, M. Adv
Synth. Catal. 2008, 350, 565.
(26) (a) Newcomb, M.; Toy, P. H. Acc. Chem. Res. 2000, 33, 449. (b)
Baldwin, J. E. Chem. Rev. 2003, 103, 1197.
(1) For selected reviews on Pd-catalyzed reactions, see: (a) Handbook of
Organopalladium Chemistry for Organic Synthesis; Negishi, E.; John Wiley &
Sons: West Sussex, U.K., 2003. (b) In Metal-Catalyzed Cross-Coupling
Reactions, 2nd ed.; de Meijere, A.; Diederich, F.; Eds.; Wiley-VCH: Wein-
heim, Germany, 2004, 815. (c) Selander, N.; Szabó, K. J. Chem. Rev. 2011,
111, 2048. (d) Molnar, A. Chem. Rev. 2011, 111, 2251. (e) Knappke, C. E.
I.; Wangelin, A. J. Chem. Soc. Rev. 2011, 40, 4948. (f) Seechun, C. J.; Kitch-
ing, M. O.; Colacot, T. J.; Snieckus, V. Angew. Chem., Int. Ed. 2012, 51,
5062.
(2) Recently, a plethora of methods involving alkyl hybrid-Pd radical in-
termediates have been reported, most of which have led to unique reactivity
and selectivity due to the intrinsic characteristics of the hybrid intermedi-
ates. However, direct formation and utilization of aryl hybrid-Pd radical
intermediates has not been reported. For a recent review on Pd involved
radical reactions, see: (a) Liu, Q.; Dong, X.; Li, J.; Xiao, J.; Dong, Y.; Liu, H.
ACS Catal. 2015, 5, 6111. For a review on catalyzed radical reactions, see:
(b) Studer, A.; Curran, D. P. Angew. Chem., Int. Ed. 2016, 55, 58.
(3) (a) Curran, D. P.; Kim, D.; Liu, H. T.; Shen, W. J. Am Chem Soc.
1988, 110, 5900. For HAT reviews, see: (b) Majetich, G.; Wheless, K.
Tetrahedron 1995, 51, 7095. (c) Radicals in Organic Synthesis Vol. 2; Re-
naud, P.; Sibi, M.P.; Wiley-VCH: Weinheim, 2001. (d) Robertson, J.;
Pillai, J.; Lush, R. K. Chem. Soc. Rev. 2001, 30, 94. (e) Nechab, M.; Mondal,
S.; Bertrand, M. P.; Chem. Eur. J. 2014, 20, 16034.
(4) For an impressive example on photoinduced desaturation reaction
involving HAT process, see: (a) Breslow, R.; Baldwin, S.; Flechtner, T.;
Kalicky, P.; Liu, S.; Washburn, W. J. Am. Chem. Soc. 1973, 95, 3251. For
efficient desaturation reactions involving both free radical and cationic
intermediates, see: (b) Voica, A.; Mendoza, A.; Gutekunst, W.R.; Fraga,
J.O.; Baran, P.S. Nat. Chem. 2012, 4, 629. (c) Hollister, K. A.; Conner, E.
S.; Spell, M. L.; Deveaux, K.; Maneval, L.; Beal, M. W.; Ragains, J. R. Angew.
Chem., Int. Ed. 2015, 54, 7837.
(5) For desilylative oxidation of silyl ethers into carbonyl derivatives,
see: (a) Reddy, M. S.; Narender, M.; Nageswar, Y. V. D. Rao, K. R. Synthesis
2005, 5, 714. (b) Chandrasekhar, S.; Mohanty, P. K.; Takhi, M. J. Org.
Chem. 1997, 62, 2628. (c) Liu, H.-J.; Han, I.-S. Synth. Commun. 1985, 15,
759. (d) Olah, G.; Balaram Gupta, G. B. Synthesis 1980, 897.
(6) For isopropyl iodide-promoted generation of a hybrid aryl Pd-
radical complex catalyzing Kumada cross-coupling reaction, see: Mano-
likakes, G.; Knochel, P. Angew. Chem., Int. Ed. 2009, 48, 205.
(7) For 1,5-HAT of aryl radical species generated in the presence of Fe
catalyst, see: (a) Yoshikai, N.; Mieczkowski, A.; Matsumoto, A.; Ilies, L.;
Nakamura, E. J. Am. Chem. Soc. 2010, 132, 5568. For 1,5-HAT of aryl radi-
cal species generated in the presence of Ni catalyst, see: (b) Wetjes, W. C.;
Wolfe, L.C.; Waller, P. J.; Kalyani, D. Org. Lett. 2013, 15, 5986.
(8) For a review on formation of hybrid transition metal-radical alkyl
species of groups 10 - 11, see: Jahn, U. Top. Curr. Chem. 2012, 320, 323.
(9) For examples of photoinduced Cu-catalyzed transformations involv-
ing alkyl iodides, see: (a) Ratani, T. S.; Bachman, S.; Fu, G. C.; Peters, J. C.
J. Am. Chem. Soc. 2015, 137, 13902. (b) Do, H.-Q.; Bachman, S.; Bissem-
ber, A. C.; Peters, J. C.; Fu, G. C. J. Am. Chem. Soc. 2014, 136, 2162. (c)
Bissember, A. C.; Lundgren, R. J.; Creutz, S. E.; Peters, J. C.; Fu, G. C.
Angew. Chem., Int. Ed. 2013, 52, 5129. For examples of photoinduced Cu-
catalyzed multi-component and cross coupling reactions, see: (d) Sagade-
van, A.; Ragupathi, A.; Hwang, K. C. Angew. Chem., Int. Ed. 2015, 54,
13896. (e) Sagadevan, A.; Hwang, K. C. Adv. Synth. Catal. 2012, 354, 3421.
(10) For a review on UV-induced Pd-catalyzed transformations involv-
ing alkyl iodides, see: Sumino, S.; Fusano, A.; Fukuyama, T.; Ryu, I. Acc.
Chem. Res. 2014, 47, 1563.
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
(27) Satoh, T.; Miura, M. Top. Organomet. Chem. 2005, 14, 1.
4
ACS Paragon Plus Environment

Page 5 of 5
Journal of the American Chemical Society
1
2
3
4
TOC Graphics
5
6
7
8
9
Direct Generation of Hybrid Pd-
Radical Species from Ar-I and Pd(0)
Hybrid Pd-Radical
Involved in HAT Process
I
Pd(I)I
H
Si
Si
Si
O
Si
Ph
O
O
O
Pd(I)I
Pd-cat.
H
H
1,5 HAT
Blue LED
room temp
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
Valuable Synthons
29 examples
40 - 99%
no exogenous
photosensitizers
or oxidants!
General, Efficent, and Mild Oxidation of Silyl Ethers
5
ACS Paragon Plus Environment