Oxidative coupling of Michael acceptors with aryl nucleophiles produced through rhodium-catalyzed C-C bond activation

Article abstract of DOI:10.1039/c7ob01212h

Utilizing rhodium catalysis, aryl nucleophiles generated via carbon-carbon single bond activation successfully undergo oxidative coupling with Michael acceptors. The reaction scope encompasses a broad range of nucleophiles generated from quinolinyl ketones as well as a series of electron deficient terminal alkenes, illustrating the broad potential of intersecting carbon-carbon bond activation with synthetically useful coupling methodologies. The demonstrated oxidative coupling produces a range of cinnamyl derivatives, several of which are challenging to prepare via conventional routes.

Full text of DOI:10.1039/c7ob01212h

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: C. E. Gregerson,
K. N. Trentadue, E. J. Phipps, J. K. Kirsch, K. M. Reed, G. D. Dyke, J. H. Jansen, C. B. Otteman, J.
Stachowski and J. B. Johnson, Org. Biomol. Chem., 2017, DOI: 10.1039/C7OB01212H.
This is an Accepted Manuscript, which has been through the
Volume 14 Number
1 7 January 2016 Pages 1–372
Royal Society of Chemistry peer review process and has been
accepted for publication.
Organic &
Biomolecular
Chemistry
www.rsc.org/obc
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1477-0520
COMMUNICATION
Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
rsc.li/obc

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 1 of 7
View Article Online
DOI: 10.1039/C7OB01212H
Organic & Biomolecular Chemistry
ARTICLE
Oxidative Coupling of Michael Acceptors with Aryl Nucleophiles
produced through Rhodium-Catalyzed C-C Bond Activation
Received 00th January 20xx,
Accepted 00th January 20xx
Caroline E. Gregerson,a Kathryn N. Trentadue,a Erik J. T. Phipps,a Janelle K. Kirsch,a Katherine M.
Reed,a Gabriella D. Dyke,a Jacob H. Jansen,a Christian B. Otteman,a Jessica L. Stachowski,b Jeffrey
B. Johnson*a
DOI: 10.1039/x0xx00000x
www.rsc.org/
Utilizing rhodium catalysis, aryl nucleophiles generated via carbon-carbon single bond activation successfully undergo
oxidative coupling with Michael Acceptors. The reaction scope encompasses a broad range of nucleophiles generated from
quinolinyl ketones as well as a series of electron deficient terminal alkenes, illustrating the broad potential of intersecting
carbon-carbon bond activation with synthetically useful coupling methodologies. The demonstrated oxidative coupling
produces a range of cinnamyl derivatives, several of which are challenging to prepare via conventional routes.
Within the realm of organic synthetic methodology, there is a
continual search for new functional groups that may be
utilized for new and transformative reactions.1 With the
dramatic rise in utility over the past two or three decades, C-H
bonds can now be considered a viable functional group for a
broad range of synthetically useful transformations.2,3 In a
similar vein, the activation and functionalization of C-C single
bonds has begun a similar rise, as evidenced by a growing
number of recent reviews in this area.4,5
The use of a covalently attached directing group to enforce
proximity of a transition metal has proven to be a successful
strategy to induce the activation of unstrained C-C bonds.6,7
The 8-substituted quinolinyl ring system pioneered by Suggs
and coworkers is well established—when utilized with acyl
substitution, carbon-carbon bond activation leads to a 5-
membered metalacycle that stabilizes the rhodium (III)
intermediate while also preventing decarbonylation (Scheme
1, intermediate A).8,9 Beyond the work by Suggs and Jun, this
directing group has been used to great effect by Douglas and
coworkers, who have achieved the highly successful
intramolecular rhodium-catalyzed alkene carboacylation of
Scheme 1. Interception of proposed rhodium(III) intermediate.
To better understand the process of C-C single bond activation
in systems containing the 8-quinolinyl directing group, our
group performed extensive mechanistic investigation of the
intramolecular alkene carboacylation reported by Douglas,
ultimately identifying primary intermediates and profiling the
kinetic behavior of this reaction with two catalysts and a range
of substrates.12 Our studies suggest that putative Rh(III)
intermediate A, presumably formed upon oxidative addition of
rhodium into the carbon-carbon single bond of the quinolinyl
ketone, has a sufficient lifetime in solution to be intercepted
via an intermolecular reaction (Scheme 1). Our group has
successfully demonstrated this strategy in the establishment of
conditions for the interconversion of quinolinyl ketones with
boronic acids.13 Herein we describe the extension of this
strategy to the oxidative coupling of aryl nucleophiles
generated from quinolinyl ketones with Michael acceptors to
form a variety of substituted cinnamyl species, several of
which are extremely challenging to make via traditional
methods.
quinolinyl
ketones
containing
pendant
olefins.10
Intermolecular alkene acylation has proven significantly more
challenging, with Douglas presenting limited success with
norbornenes in the face of competing C-H activation.11
Results and Discussion
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 2 of 7
View Article Online
DOI: 10.1039/C7OB01212H
ARTICLE
Journal Name
Previous mechanistic studies performed by our group on
Nomura’s Pd-catalyzed β-aryl elimination illustrated a dramatic
enhancement of C-C bond activation for ortho-fluorinated aryl
groups, 14,15 a phenomenon attributed to the stabilization of a
Pd-aryl intermediate.16 In this system, the presence of an o-
fluorinated arene promises to promote C-C bond activation
and stabilize the rhodium (III) intermediate A, thus facilitating
intermolecular reactivity. With this in mind, we began our
exploration of substrates and conditions utilizing o-fluorinated
Scheme 3. Observed quinoline-containing byproduct
quinolinyl ketone 1. While a significant number of alkenes
resulted in no reaction with the quinolinyl ketone, we were
delighted to observe significant reaction of the quinolinyl
starting material with the use of methyl acrylate (Scheme 2).
Upon investigation of the product mixture, however, no
With reaction conditions in hand, we sought to investigate the
importance of the ortho-fluoro substitution by evaluating a
series of other quinolinyl ketones under the standard reaction
conditions. Although the presence of the o-fluoro substitution
greatly enhances the rate of the reaction, similar reactivity is
observed with other quinolinyl ketones after 16 h at 130 °C. A
significant range of aryl functionality and substitution patterns
are compatible with the reaction conditions. Using similar
ortho-substituted quinolinyl ketone substrates, alkyl, alkoxy
and trifluoromethyl substitutions all proceed in the reaction,
albeit with reduced yields relative to the initial fluorinated
species (Table 1, entries 2-4). In all cases, reduced yields are
the result of unreacted quinolinyl ketone starting material and
not the formation of undesired byproducts.22 Notably, the
ortho-chlorinated species works well in the reaction (entry 5),
producing the desired cinnamate ester in high yields with no
signs of byproducts due to oxidative addition into the carbon-
chlorine bond. In addition to ortho substitution, the reaction
also readily proceeds with a series of meta (entries 6-9) and
para (entries 10-13) substituents, as well as with the
unsubstituted phenyl ring (entry 14). While not a perfect
correlation, substrates containing electron withdrawing
functionality generally undergo more efficient reaction than
comparable electron rich species. Efforts to extend the
reactivity to a heterocylic pyridyl group (entry 15) or furyl
group (entry 16) proved unsuccessful. Similarly, alkyl quinolinyl
ketones also failed to provide the desired product.
carboacylation product
B
was observed. Instead, the major
, presumably formed via an
species observed was alkene
2
insertion/elimination process reminiscent of an oxidative Heck
reaction.17 Notably, o-substituted cinnamate esters of this
form are challenging to prepare, with few reliable methods
reported in the literature.18
Scheme 2. Observation of oxidative coupling product.
Upon observation of this initial reactivity, efforts were made to
optimize the reaction conditions for the production of
disubstituted alkene
rhodium catalysts, solvents, and concentrations, the highest
conversion of the o-fluorinated quinolinyl ketone was
2. After exploration of a number of
1
achieved in the presence of 10 equivalents of methyl acrylate
and 5 mol% [Rh(C2H4)2Cl]2 in toluene, heated in a sealed tube
at 130 °C for 4 hours.19 Under these optimized conditions, the
quinolinyl ketone is quantitatively converted to the desired
product, which was isolated solely as the trans isomer in 79%
yield.20 As evidenced by 1H NMR spectroscopy, a number of
quinolinyl species are observed as byproducts of the reaction,
most notably quinolinyl ketone
3, which results from the
insertion of an equivalent of methyl acrylate. This compound
was isolated in 22% based on the starting quinolinyl ketone,
and is observed by GC/MS in amount ranging from 0% to 35%
in reactions using methyl acrylate. No clear trend in the
amount of
3
versus reaction conditions was observed.21
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 3 of 7
View Article Online
DOI: 10.1039/C7OB01212H
Journal Name
ARTICLE
Entrya
1
Ar
Product
Yield (%)b
59 (86)
76 (99)
43 (52)
72 (95)c
71 (95)
68 (93)
20 (41)
71 (92)
79 (99)
(16)
Ph
19
20
21
22
23
24
25
26
27
28
29
2
3
2-F-C6H4
2-OCH3-C6H4
2-CH3-C6H4
3-F-C6H4
Table 1: Reaction of substituted quinolinyl ketones with methyl acrylate.
4
5
6
3-CF3-C6H4
4-F-C6H4
7
8
4-CF3-C6H4
4-OCH3-C6H4
4-CH3-C6H4
2-pyridyl
9
10
11
< 5
Entrya
1
Ar
Product
Yield (%)b
79 (99)
34 (57)
38 (51)c
12 (33)
77 (87)
73 (92)
76 (96)c
68 (95)
75 (98)
40 (42)
72 (91)
21 (35)
46 (56)c
38 (45)
<5
a
Standard reaction conditions: Quinolinyl ketone, N,N-dimethylacrylamide (5
2-F-C6H4
2
4
equiv), [Rh(C2H4)2Cl]2 (5 mol%) in toluene (1 mL), heated in a sealed tube at 130
2
2-CF3-C6H4
2-OCH3-C6H4
2-CH3-C6H4
2-Cl-C6H4
3-OCH3-C6H4
3-CF3-C6H4
3-NO2-C6H4
3,5-(CF3)2-C6H4
4-F-C6H4
b
°C for 16 hours. Values in parentheses are conversions based upon GC/MS
analysis. c 10 mol% of [Rh(C2H4)2Cl]2 used.
3
5
4
6
5
7
In addition to exploring functionality on the quinolinyl ketone,
we also sought to explore the range of alkenes amenable to
this reaction. Following our success with methyl acrylate and
N,N-dimethylacrylamide, other terminal Michael acceptors,
including acrylonitrile, ethyl vinyl sulfone, and ethyl vinyl
ketone were examined for reactivity (Scheme 4). Despite
significant challenges in isolation due to the required excess
alkene and the similar polarities of the products and Michael
acceptors, both ethyl vinyl ketone and ethyl vinyl sulfone were
successfully utilized in the reaction. 1,1-disubstituted alkene
methyl methacrylate provided desired product, albeit in a
nearly 1:1 ratio of stereoisomers (products 30 and 31).
Unfortunately, any efforts to expand this reactivity to less
polar alkenes or 1,2-disubstituted Michael acceptors were
unsuccessful, producing trace, if any, desired product.23 In
these cases, unreacted starting material is recovered after
typical reaction time and continued exposure to the reaction
conditions ultimately leads to starting material decomposition
over several days.
6
8
7
9
8
10
11
12
13
14
15
16
17
18
9
10
11
12
13
14
15
16
4-CF3-C6H4
4-OCH3-C6H4
4-CH3-C6H4
Ph
2-pyridyl
2-furyl
<10
a Standard reaction conditions: Quinolinyl ketone, methyl acrylate (10 equiv), 5
mol% [Rh(C2H4)2Cl]2 in toluene (1 mL), heated in a sealed tube at 130 °C for 16
hours. b Values in parentheses are conversions based upon GC/MS analysis. 10
c
mol% of [Rh(C2H4)2Cl]2 used.
Beyond the use of methyl acrylate, N,N-dimethylacrylamide
was also examined with a broad range of quinolinyl ketones.
The reactions with this alternative Michael acceptor generally
proceed in moderate to good yields with a range of functional
group compatibility, while also tolerating ortho, meta, and
para substitution. Notably, the product yields with the
acrylamide tend to be higher than those observed using
methyl acrylate, particularly with more neutral and electron
rich starting materials. For example, the use of the p-
methoxyphenyl-substituted quinolinyl ketone resulted in only
a 21% yield with methyl acrylate (Table 1, entry 12), but the
same ketone reacts with N,N-dimethylacrylamide to provide
27 in 79% yield (Table 2 entry 9.)
Table 2: Reaction of substituted quinolinyl ketones with N,N-
dimethylacrylamide.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 4 of 7
View Article Online
DOI: 10.1039/C7OB01212H
ARTICLE
Journal Name
as a byproduct in several reactions utilizing methyl acrylate as
the Michael acceptor, suggesting its formation via alkene
insertion and subsequent reductive elimination. Traces of a
number of additional quinoline-containing species have been
observed by GC/MS and NMR spectroscopy, indicating a
likelihood that multiple alkene insertions lead to oligomeric
byproducts which both complicate isolation and consume
excess Michael acceptor.
Scheme 4. Product scope with a range of Michael Acceptorsa,b
O
Ar
[Rh(C2H4)2Cl]2
(5 mol%)
N
EWG
+
EWG
Ar
toluene
N2, 130 o
C
EWG
O
Ar
O
N
N
G (byproduct)
[Rh]
Ar
O
[Rh]
N
EWG
O
[Rh]
N
EWG
Ar
A
F
EWG
[Rh]
H
O
EWG
O
[Rh]
N
N
- [Rh]
D
C
a
+ [Rh]
H
O
Ar
Standard reaction conditions: Quinolinyl ketone, Michael acceptor (5 equiv),
EWG
[Rh(C2H4)2Cl]2 (5 mol%) in toluene (1 mL), heated in a sealed tube at 130 °C for 16
hours. b Values in parentheses are conversions based upon GC/MS analysis. c Recovered
as a mixture of diastereomers (approximately 1:1).
N
E
Our proposed mechanism for this transformation (Scheme 5)
relies largely upon our previous investigation of the
intramolecular carboacylation of tethered alkenes.12 We
propose that the reaction begins with rhodium coordination to
the Lewis basic site of the quinolinyl moiety, placing the metal
in proximity to the targeted C-C bond.8 Formal oxidative
addition of rhodium into the aryl carbonyl leads to formation
Scheme 5. Proposed catalytic cycle.
To gain rudimentary insight into the reaction mechanism,
intermolecular competition reactions were performed to
ascertain the relative rates of C-C activation and alkene
insertion (Scheme 6). To this end, a single reaction flask
of rhodium(III) intermediate
A. This intermediate then
containing quinolinyl ketone
1 was treated with 5 equivalents
coordinates to the exogenous Michael acceptor, which inserts
into the rhodium-aryl bond. While we initially anticipated
each of methyl acrylate and N,N-dimethylacrylamide under
otherwise standard reaction conditions. The use of periodic 1H
NMR spectroscopy to follow the reaction demonstrated that
product 20, stemming from reaction with the acrylamide, was
reductive elimination from this intermediate
of the beta hydrogen allows β-hydride elimination, yielding the
oxidative Heck-type product and rhodium hydride . While
reductive elimination from would yield quinolinyl aldehyde
, this aldehyde is never observed in solution, as C-H activation
C, the presence
D
produced at a significantly greater rate than product
from methyl acrylate. After 10 minutes, 34% of ketone
undergone conversion, resulting in a 2:1 ratio of amide 20 to
ester . Similarly, after 36 minutes of reaction, ketone
conversion reached 56%, with a 3:2 ratio of 20 to . Related
2
formed
D
1
had
E
of this species presumably occurs more rapidly than C-C
activation of the original substrate. Instead, it is proposed that
2
2
intermediate
D
is intercepted by excess Michael acceptor.
. As
(Scheme 3) has been observed
experiments have been performed with methyl acrylate in
competition with ethyl vinyl ketone or ethyl vinyl sulfone. In
Insertion and elimination could lead to compound
G
described above, compound
3
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 5 of 7
View Article Online
DOI: 10.1039/C7OB01212H
Journal Name
ARTICLE
3
4
(a) R. H. Crabtree, Chem. Rev. 1985, 85, 245. (b) W. D. Jones,
Nature 1993, 364, 676.
(a) P.-H. Chen, B. A. Billett, T. Tsukamoto, G. Dong, ACS Catal.
2017, 7, 1340. (b) G. Dong, Ed. C-C Bond Activation, Springer,
each of these cases, selectivities in excess of 10:1 favoring the
acrylate product were observed. Studies with m-CF3 and 3,5-
(CF3)2 substituent quinolinyl ketones generated similar results.
The distinct selectivity between Michael acceptors suggests
that alkene insertion is the turnover limiting step of the
catalytic cycle, an observation that aligns with reactivity
observed for the intramolecular carboacylation catalyzed by
the same catalyst.10,12b
New York, 2014. (c) L. Souillart, N. Cramer, Chem. Rev. 2015
,
115, 9410. (d) M. Murakami, Y. Ito, in Activation of
Unreactive Bonds and Organic Synthesis; (Ed.: S. Murai),
Springer: Berlin, 1999; p 97. (e) M. Murakami, N. Chantani,
Eds. Cleavage of Carbon-Carbon Single Bonds by Transition
Metals, Wiley-VCH, Weinheim, 2016
.
5
(a) T. Kondo, Eur. J. Org. Chem. 2016, 2016, 1232. (b) P.-H.
Chen, G. Dong, Chem. Eur. J. 2016, 22, 18290. (c) A. Flores-
Gaspar, R. Martin, Synthesis 2013, 45, 563. (d) T. Seiser, T.
Saget, D. N. Tran, N. Cramer, Angew. Chem. Int. Ed. 2011, 50,
7740. (e) A. K. Sadana, R. K. Saini, W. E. Billups, Chem Rev.
2003, 103, 1539. (f) J. C. Namyslo, D. E. Kaufmann, Chem Rev.
2003, 103, 1485. (g) D. Bellus, B. Ernst, Angew. Chem. Int. Ed.
1988, 27, 797. (h) B.-S. Li, Y. Wang, Z. Jin, P. Zheng, R.
Ganguly, Y. R. Chi, Nature Communications, 2015, 6, 1. (i) M.
Murakami, H. Amii, Y. Ito, Nature, 1994, 370, 540.
6
7
8
9
For examples of directing-group mediated C-C activation and
functionalization, see: (a) S. C. Bart, P. J. Chirik, J. Am. Chem.
Soc. 2003, 125, 886. (b) A. H. Hoveyda, D. A. Evans, G. C. Fu,
Chem. Rev., 1993, 93, 1307. (c). X.-G. Zhang, H.-X. Dai, M.
Wasa, J.-Q. Yu, J. Am. Chem. Soc., 2012, 134, 11948
For pyridine directed reactivity, see: (a) Z.-Q. Lei, H. Li, Y. Li,
X.-S. Zhang, K. Chen, X. Wang, J. Sun, Z.-J. Shi, Angew. Chem.,
Int. Ed. 2012, 51, 2690. (b) Z.-Q. Lei, F. Pan, H. Li, Y. Li, X.-S.
Zhang, K. Chen, X. Wang, Y.-X. Li, J. Sun, Z.-J. Shi, J. Am.
Chem. Soc. 2015, 137, 5012.
Scheme 6. Intermolecular competition between Michael Acceptors.
(a) J. W. Suggs, J. Am. Chem. Soc. 1978, 100, 640. (b) J. W.
Suggs, M. J. Wovkulich, S. D. Cox, Organometallics 1985, 4,
Conclusions
1101. (c) J. W. Suggs, S. D. Cox, J. Organomet Chem. 1981
221, 199. (d) J. W. Suggs, C.-H. Jun, J. Am. Chem. Soc. 1984
106, 3054.
,
,
The methodology presented herein demonstrates the
oxidative coupling of aryl substituents derived from the C-C
bond activation of quinolinyl ketones with Michael acceptors.
The transformation tolerates a range of functional groups, and
readily couples substituted aromatics. Although many of the
products can be accessed via known Heck chemistry, the newly
reported reaction illustrates the promise of utilizing C-C
activation on nontrivial molecules for further functionalization,
giving a glimpse to the potential synthetic utility of carbon-
carbon single bond activation.
(a) J. Ishizu, T. Yamamoto, A. Yamamoto, Chem. Lett. 1976, 5
1091. (b) T. Yamamoto, S. Miyashita, Y. Naito, S. Komiya, T.
Ito, A. Yamamoto, Organometallics, 1982, 1, 808. (c) N.
Chatani, H. Tatamidani, Y. Ie, F. Kakiuchi, S. Murai, J. Am.
Chem. Soc. 2001, 123, 4849. (d) D. V.Gribkov, S. J. Pastine, M.
Schnürch, D. Sames, J. Am. Chem. Soc. 2007, 129, 11750.
10 (a) A. M. Dreis, C. J. Douglas, J. Am. Chem. Soc. 2009, 131,
412. For similar C-O activation directed by the 8-quinolinyl
moiety, see (b) G. T. Hoang, V. J. Reddy, H. H. K. Nguyen, C. J.
Douglas, Angew. Chem. Int. Ed. 2011, 50, 1882.
11 M. T. Wentzel, V. J. Reddy, T. K. Hyster, C. J. Douglas, Angew.
Chem. Int. Ed. 2009, 48, 6121.
12 (a) C. M. Rathbun, J. B. Johnson, J. Am. Chem. Soc. 2011, 133,
2031. (b) J. P. Lutz, C. M. Rathbun, S. M. Stevenson, B. M.
Powell, T. S. Boman, C. E. Baxter, J. M. Zona, J. B. Johnson, J.
Am. Chem. Soc. 2012, 134, 715.
13 J. M. Dennis, C. T. Compagner, S. K. Dorn, J. B. Johnson, Org.
Lett. 2016, 18, 3334.
Acknowledgements
The authors thank the National Science Foundation (CHE-
1148719) and the Henry Dreyfus Teacher-Scholar Award
Program (TH-15-030) for funding. J.B.J. acknowledges support
from the Hope College Schaap Scholars Program. J.L.S. thanks
the University of Michigan Rackham Graduate School for travel
support. Grants from the NSF for the purchase of NMR
spectrometers (CHE-0922623) and GC/MS instrumentation
(CHE-0952768) are also gratefully acknowledged.
14 (a) Y. Terao, H. Wakui, T. Satoh, M. Miura, M. Nomura, J. Am.
Chem. Soc. 2001, 123, 10407. (b) Y. Terao, H. Wakui, M.
Nomoto, T. Satoh, M. Miura, M. Nomura, J. Org. Chem. 2003
68, 5236.
,
15 J. R. Bour, J. C. Green, V. J. Winton, J. B. Johnson, J. Org.
Chem. 2013, 78, 1665.
16 The presence of an ortho-fluorine is has been calculated to
stabilized a Rh-Ar complex by 5.5 kcal/mol. See E. Clot, O.
Eisenstein, N. Jasim, S. A. Macgregor, J. E. McGrady, R. N.
Perutz, Acc. Chem. Res. 2011, 44, 333.
17 For information on the oxidative Heck reaction, see: a) L. R.
Odell, J. Saevmarker, J. Lindh, P. Nilsson, M. Larhed, in
Comprehensive Organic Synthesis, (Eds.: P. Knochel, G. A.
Molander), Elsevier, Amsterdam, 2014. pg 492. b) Y. Su, N.
Jiao, Curr. Org. Chem. 2011, 15, 3362 and references therein.
Notes and references
1
A. de Meijere, F. Diederich, Metal-catalyzed Cross-Coupling
.
Reactions, 2nd Edition; Wiley-VCH: Weinheim, 2004
J. A. Labinger, J. E. Bercaw, Nature, 2002, 417, 507.
2
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 6 of 7
View Article Online
DOI: 10.1039/C7OB01212H
ARTICLE
Journal Name
18 J. Ruan, X. Li, O. Saidi, J. Xiao, J. Am. Chem. Soc. 2008, 130,
2424.
19 See supporting information for more information of the
optimization process.
20 The cis isomer is observed in <10% abundance in many crude
reaction mixtures.
21 Resubjection of compound 3 to standard reaction conditions
leads to the slow degradation of
containing species.
3 to a variety of quinolinyl
22 In many cases, product yields can be increased with an
increase in catalyst loading, or reaction mixtures can be
resubjected to reaction conditions to provide greater
conversion of the quinolinyl ketones to product.
23 Note that intermolecular carboacylation was observed upon
reaction with norbornene. See reference 11.
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 7 of 7
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C7OB01212H
78x33mm (300 x 300 DPI)