Ambient Decarboxylative Arylation of Malonate Half-Esters via Oxidative Catalysis

Article abstract of DOI:10.1021/jacs.6b08906

We report decarboxylative carbonyl α-arylation by coupling of arylboron nucleophiles with malonic acid derivatives. This process is enabled by the merger of aerobic oxidative Cu catalysis with decarboxylative enolate interception reminiscent of malonyl-CoA reactivity in polyketide biosynthesis. This method enables the synthesis of monoaryl acetate derivatives containing electrophilic functional groups that are incompatible with existing α-arylation reactivity paradigms. The utility of the reaction is demonstrated in drug intermediate synthesis and late-stage functionalization.

Full text of DOI:10.1021/jacs.6b08906

Subscriber access provided by CORNELL UNIVERSITY LIBRARY
Communication
Ambient Decarboxylative Arylation of
Malonate Half-Esters via Oxidative Catalysis
Patrick J. Moon, Shengkang Yin, and Rylan J. Lundgren
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.6b08906 • Publication Date (Web): 13 Oct 2016
Downloaded from http://pubs.acs.org on October 13, 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
6
7
8
9
Ambient Decarboxylative Arylation of Malonate Half-Esters via Oxi-
dative Catalysis
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
Patrick J. Moon, Shengkang Yin, Rylan J. Lundgren*
Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada
Supporting Information Placeholder
arylation reactions stands in contrast to the burgeoning
ABSTRACT: We report decarboxylative carbonyl α-arylation
by coupling arylboron nucleophiles with malonic acid deriva-
tives. This process is enabled by the merger of aerobic oxida-
tive Cu-catalysis with decarboxylative enolate interception
fields of radical arylative decarboxylations of α-heteroatom
substituted acids via platinum-group metal photoredox ca-
talysis8 or the use of redox-active esters functionalized with
activators to promote bond cleavage.9
reminiscent of malonyl-CoA reactivity in polyketide biosyn-
We were inspired by the exceptionally mild conditions
under which Cu(II)-catalyzed decarboxylative aldol-type
reactions occur 3a, 10 and hypothesized that combining the use
thesis. This method allows for the synthesis of monoaryl ace-
tate derivatives containing electrophilic functional groups
that are incompatible with existing α-arylation reactivity
paradigms. The utility of the reaction is demonstrated in
drug intermediate synthesis and late-stage functionalization.
a Electrophilic decarboxylative malonate half-(thio)ester functionalizations
E
O
O
E
CO2H
G
G
– CO2
O
In the biosynthesis of polyketides and fatty acids, car-
bon–carbon bond formation proceeds via decarboxylative
cross-condensation between malonic acid derivatives such as
malonyl-CoA and enzyme-bound acyl electrophiles.1 A varie-
ty of conceptually related metal- or organocatalyzed reac-
tions have been developed, in which malonates and related
species undergo decarboxylation and coupling with carbonyl
or allylic electrophiles.2 These reactions obviate the need for
high temperatures, strongly basic mediators or prior stoichi-
ometric manipulations to generate the enolate component
(Fig 1a).3 By contrast, there are limited reports of decarboxy-
lative coupling reactions of malonate derivatives with aryl
electrophiles. Pd-catalyzed coupling of malonic acid deriva-
tives with aryl halides requires pre-deprotonation of the acid
and high temperatures (≥120 °C), presumably in order to
generate a Pd enolate via thermal decarboxylation.4 The de-
velopment of mild and robust methods for decarboxylative
α-arylation would find broad appeal, as the preparation of
polyfunctionalized monoaryl acetic acids via cross-coupling
of simple acetate derivatives remains a significant challenge
in synthetic chemistry.
polyketide and fatty acid biosynthesis
metal-catalyzed allylations
RS
Me
X
E
:
O
decarboxylative aldol-type reactions
H
R
b Cu mediated coupling of aryl boron reagents and heteroatom nucleophiles
copper
oxidant
B(OR)2
Nuc
FG
Nuc–H
FG
Nuc–H:
orthogonal to classical cross-coupling
exceptionally mild reaction conditions
amines, alcohols,
sulfides, halides
c Concept : nucleophilic arylation of malonic acids via merged oxidative
decarboxylative catalysis (a + b)
FG
(RO)2B
O
catalytic [Cu]
O
FG
CO2H
G
G
– CO2
room temperature, air
[ambient conditions]
d Examples of drugs that contain polyfunctionalized aryl acetic acid moieties
NHiPr
OH
Me
O
O
O
Unstabilized acetates can be arylated via in situ enoliza-
tion under strongly basic conditions incompatible with pro-
tic or electrophilic functionality5 or subjected to stoichio-
metric manipulations to generate pre-formed silyl- or metal
enolates.6 These strategies significantly reduce synthetic effi-
ciency and utility in complex molecule synthesis. Common
methods used in medicinal chemistry campaigns requir-
ing α-aryl carbonyl compounds remain traditional SNAr or
metal-catalyzed coupling reactions involving dialkyl malo-
nates, followed by hydrolysis and thermal decarboxylation.
Thus, access to complex monoaryl acetic acids (such as those
in Fig 1d) generally requires multi-step, substrate specific
processes.7 The dearth of mild malonic acid decarboxylative
O
F
F
O
O
N
N
H
N
F
H2N
CO2H
Prasugrel
Lumacaftor
Atenolol
S
Cl
O
O
Me
S
CO2H
OEt
OAc
Cl
HN
Me
O
O
O
N
H
O
HO
N
F
NHtBu
Repaglinide
AMG 853
Figure 1. Reactivity of malonic acid derivatives, oxidative cou-
pling and α-aryl carbonyl structures in bioactive molecules.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 5
of a Cu(II) (pre)catalyst, a malonic acid derivative, and an
boroxine, or free boronic acid forms. Alternative Cu(II) salts
1
2
3
4
5
6
7
8
appropriate aryl coupling partner could allow for decarboxy-
lative C–C bond formation without the detriments of thermal
activation and strongly basic conditions. We were encour-
aged by the mild and robust nature of oxidative copper(II)-
catalyzed cross-coupling reactions of two nucleophilic part-
ners.11 The Cu-catalyzed oxidative arylation of heteroatom
nucleophiles with aryl boronic acids for the preparation of
anilines and phenols (Fig 1b)12 occurs under mild conditions
using the O2 present in ambient air as the oxidant. This reac-
tivity has been extended to the arylation of carbon-based
nucleophiles, including the stoichiometric arylation of acti-
vated methylenes.13 Thus, a new reactivity platform that
merges ambient decarboxylation of malonic acids and aero-
bic copper catalysis could allow for enolate arylation to occur
with unprecedented tolerance towards reactive functional
groups, providing a solution to the difficulties associated
with synthesizing aryl acetates (Fig 1c). The abundance of α-
aryl carbonyl units found embedded in the core of pharma-
ceuticals, ranging from relatively simple NSAIDs like
Naproxen to structurally complex, densely functionalized
bioactive molecules, such as Lumacaftor, Prasugrel, and Rep-
aglinide, provided clear motivation for development of such
a method (Fig 1d).
performed poorly, but Cu(I) species, such as Cu(MeCN)4PF6
or CuI could be used as catalysts; in these cases a significant
induction period was observed.16 These results suggest that
the nature of the counterion of the Cu (pre)catalyst
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
We were cognizant of the potential difficulties associated
with realizing an oxidative decarboxylative arylation reaction
involving malonic acids, particularly as carboxylic acids
themselves are viable partners for copper-catalyzed O-
arylation14 and that irreversible decarboxylation or proto-
deborylation would result in unreactive substrates. Attempts
to oxidatively couple enolate equivalents with aryl boron
reagents mediated by copper involving in-situ deprotonation
or the use of pre-formed silyl ketene acetals were not suc-
cessful. These results highlight an inherent difficulty in oxi-
dative coupling reactions,15 as the use of preformed enolates
resulted in exclusive formation of homocoupling products
derived from both reaction partners without detectable
cross-coupling. Monoethyl malonate however was observed
to engage in highly selective catalytic decarboxylative cross-
coupling with 3-iodophenyl boronic neopentyl ester
[B(neop)] in air at room temperature with Cu(OTf)2 to give
the desired product in 83% yield (Fig 2). No cross- or homo-
coupling at the reactive electrophilic aryl iodide site, or com-
peting arylation of the carboxylic acid was observed. The
process can be scaled up to deliver gram quantities of aryl
acetate product by using an uncapped round bottom flask
(77% yield, 1.6 grams of product). To briefly describe key
experimental parameters in reaction development, neopentyl
glycol derived boronic esters were superior to pinacol ester,
Figure 3. Scope of the Cu-catalyzed decarboxylative cross-
coupling of malonate derivatives and aryl boronic esters.
Figure 2. Overview of reaction discovery and optimization.
ACS Paragon Plus Environment

Page 3 of 5
Journal of the American Chemical Society
influences reactivity more than the initial oxidation state.
straightforward and predictable manner to give two distinct
1
2
3
4
5
6
7
8
compounds (5d and 5e) from a common starting material.
Due to the mild, ambient nature of the transformation,
the oxidative decarboxylative α-arylation reaction is amena-
ble to coupling substrates containing a host of functional
groups that would be potentially complicating with estab-
lished methods (Fig 3a). The reaction tolerates alkyl halides
(2d, 2x), aryl halides (2a-2h, 2l, 2p, 2r, 2u, 2w), enolizable
ketones (2t) and esters (2z), Michael acceptors (2w), elec-
tron-rich olefins (2f), nitriles (2j, 2q) as well as protic nitro-
gen (2v, 2y, 4b) and oxygen (2y) groups. The ester moiety
can range from relatively simple, easy to dealkylate groups,
such as methyl or benzyl, to more complex functional group-
containing species (2d-2f). Heteroaryl boronic esters such as
substituted pyridines (3a–3e), quinolines (3f), and pyrim-
idines (3g-3i), including halogenated examples, are smoothly
cross-coupled to give heteroaryl acetate adducts. Malonic
monoamides undergo decarboxylative (hetero)arylation un-
der standard conditions, including NH-amides (4b), aryl-
alkyl (4c) and dialkyl amides (4d, 4e). While beta-keto acids
are not currently viable cross-coupling partners, Weinreb
amides, versatile ketone surrogates, can be employed with
both halogenated arenes and pyridines (4f–h).
The applicability of this new copper-catalyzed decarboxy-
lative arylation reaction was demonstrated in the preparation
of the α-aryl cyclopropyl ketone core of Prasugrel (Fig 5a,
6a), which was synthesized in 51% yield in two steps via de-
carboxylative arylation of the Weinreb amide derivative fol-
lowed by treatment with cyclopropyl Grignard reagent. The
arylated core of Lumacaftor was prepared by coupling the
PMP-protected pyridyl α-carboxy amide and a functionalized
aryl B(neop) reagent (Fig 5b) to deliver the target 6b in 74%
yield.
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
The potential to functionalize complex molecules using
this ambient decarboxylative strategy was tested on a variety
of arene-containing drug molecules. The complex alkaloid
Nicergoline could be borylated quantitatively and cross-
coupled to monoethyl malonate in 57% yield (7a).
A large range of aryl boronic acids and esters are com-
mercially available; however in cases in which the aryl boron
reagent is not immediately available, the oxidative coupling
can be conducted in tandem with an arene borylation step
(Fig. 4). Aryl halides can be subjected to Pd-catalyzed boryla-
tion17 to generate the corresponding aryl–B(neop) reagent
that can be used after extractive workup without chromato-
graphic purification to give 5a. Ir- catalyzed C–H borylation18
can be used to generate products of formal carbonyl α-C–H
arylation (5b). Leveraging the combined power of metal-
catalyzed borylation and Cu-catalyzed decarboxylative malo-
nate arylation, regiocontrolled alkylation of substituted aro-
matics such as chloroarene 5c can be achieved in a
Figure 5. Applications of Cu-catalyzed decarboxylative malonate
arylation in complex molecule synthesis and functionalization.
Figure 4. Sequential arene borylation/decarboxylative coupling
reactions
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 5
H.; Lee, J. W.; List, B.; Song, C. E., Angew. Chem. Int. Ed. 2013, 52,
NBoc-Paroxetine could be selectively alkylated at one of
the five aryl C–H positions to deliver 7b via an Ir-catalyzed
diborylation/mono-deborylation strategy followed by decar-
boxylative cross-coupling. Indometacin ethyl ester could be
diversified into two unique derivatives by employing either
Pd-catalyzed aryl chloride borylation followed by oxidative
coupling (7c), or Ir-catalyzed C–H borylation followed by
oxidative coupling (7d) to give the aryl acetate derivatives in
synthetically useful yields (63% and 53% oxidative coupling
yield respectively). These results support the prospect that
malonic half esters may be used as two carbon units to syn-
thesize and diversify drug-like molecules in medicinal chem-
istry campaigns by employing the reactivity platform de-
scribed herein.
12143-12147; (h) Li, C. K.; Breit, B., J. Am. Chem. Soc. 2014, 136, 862-
865; (i) Bahlinger, A.; Fritz, S. P.; Wennemers, H., Angew. Chem. Int. Ed.
2014, 53, 8779-8783.
1
2
3
4
5
6
7
8
4. (a) Shang, R.; Ji, D.-S.; Chu, L.; Fu, Y.; Liu, L., Angew. Chem. Int. Ed.
2011, 50, 4470-4474; (b) Feng, Y.-S.; Wu, W.; Xu, Z.-Q.; Li, Y.; Li, M.;
Xu, H.-J., Tetrahedron 2012, 68, 2113-2120. (c) For the Cu/Mg promoted
decarboxylative coupling of iododpyridines and a malonic half-ester at
100 ºC : Ho, J. Z.; Braun, M. P., J. Label Compd. Radiopharm. 2007, 50,
277-280. For examples of Pd-catalyzed cross-coupling of malonates fol-
lowed by thermal dealkyoxycarbonylation or deacylation see: d) Song, B.
R.; Rudolphi, F.; Himmler, T.; Goossen, L. J., Adv. Synth. Catal. 2011,
353, 1565-1574 e) Zeevaart, J. G.; Parkinson, C. J.; de Koning, C. B.;
Tetrahedron Lett. 2007, 48, 3289-3293. For the decarboxylative coupling
of oxalate monoesters with aryl boron reagents see (f) Miao, J.-M.; Fang,
P.; Jagdeep, S.; and Ge, H.-B. Org. Chem. Front. 2016, 3, 243-250.
5. Limited to t-Bu esters: (a) Biscoe, M. R.; Buchwald, S. L., Org. Lett.
2009, 11, 1773-1775; (b) Jorgensen, M.; Lee, S.; Liu, X. X.; Wolkowski,
J. P.; Hartwig, J. F., J. Am. Chem. Soc. 2002, 124, 12557-12565.
6. (a) Kosugi, M.; Negishi, Y.; Kameyama, M.; Migita, T., Bull. Chem.
Soc. Japan 1985, 58, 3383-3384; (b) Agnelli, F.; Sulikowski, G. A., Tet-
rahedron Lett. 1998, 39, 8807-8810; (c) Hama, T.; Liu, X. X.; Culkin, D.
A.; Hartwig, J. F., J. Am. Chem. Soc. 2003, 125, 11176-11177.
7. Alternative approaches: cross-coupling of α-halo esters and aryl nucle-
ophiles (a) Goossen, L. J., Chem. Commun. 2001, 669-670; photoredox
approaches (b) Jang, H. L.; Kim, H. T.; Cho, E. J.; Joo, J. M. Asian J. Org.
Chem. 2015, 4, 1386-1391; metal catalyzed carbonylations of benzyl
halides (c) Giroux, A.; Nadeau, C.; Han, Y. X., Tetrahedron Lett. 2000,
41, 7601-7604; iodide and acid mediated reductions of mendelic acids (d)
Milne, J. E.; Storz, Colyer, T. J.; Thiel, O. R.; Seran, M. D.; Larsen, R. D.;
Murry, J. A. J. Org. Chem. 2011, 76, 9519-9524; oxidative deaminative
arylation with aryl boronic acids (e) Wu, G. J.; Deng, Y. F.; Wu, C. Q.;
Zhang, Y.; Wang, J. B.; Angew. Chem. Int. Ed. 2014, 53, 10510-10514;
and silyl ketene acetal arylation with pyridine N-oxides (f) Londregan, A.
T.; Burford, K.; Conn, E. L.; Hesp, K. D., Org. Lett. 2014, 16, 3336-3339.
8. (a) Zuo, Z. W.; Ahneman, D. T.; Chu, L. L.; Terrett, J. A.; Doyle, A.
G.; MacMillan, D. W. C., Science 2014, 345, 437-440; (b) Zuo, Z. W.;
MacMillan, D. W. C., J. Am. Chem. Soc. 2014, 136, 5257-5260.
9. (a) Cornella, J.; Edwards, J. T.; Qin, T.; Kawamura, S.; Wang, J.; Pan,
C. M.; Gianatassio, R.; Schmidt, M.; Eastgate, M. D.; Baran, P. S., J. Am.
Chem. Soc. 2016, 138, 2174-2177; (b) Huihui, K. M. M.; Caputo, J. A.;
Melchor, Z.; Olivares, A. M.; Spiewak, A. M.; Johnson, K. A.; DiBene-
detto, T. A.; Kim, S.; Ackerman, L. K. G.; Weix, D. J., J. Am. Chem. Soc.
2016, 138, 5016-5019; (c) Wang, J.; Qin, T.; Chen, T.-G.; Wimmer, L.;
Edwards, J. T.; Cornella, J.; Vokits, B.; Shaw, S. A.; Baran, P. S., Angew.
Chem. Int. Ed. 2016, 55, 9676-9679.
10. C–C bond formation preceeds decarboxylation in Cu-catalyzed decar-
boxylative aldol reactions: Fortner, K. C.; Shair, M. D., J. Am. Chem. Soc.
2007, 129, 1032-1033.
11. Shi, W.; Liu, C.; Lei, A. W., Chem. Soc. Rev. 2011, 40, 2761-2776.
12. Qiao, J. X.; Lam, P. Y. S., In Boronic Acids: Preparation and Applica-
tions in Organic Synthesis, Medicine and Materials, 2 ed.; Hall, D. G., Ed.
Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, 2011; 315-361.
13. (a) Stevens, J. M.; MacMillan, D. W. C., J. Am. Chem. Soc. 2013, 135,
11756-11759; (b) Moon, P. J.; Halperin, H. M.; Lundgren, R. J., Angew.
Chem. Int. Ed. 2016, 55, 1894-1898.
14. Huang, F.; Quach, T. D.; Batey, R. A., Org. Lett. 2013, 15, 3150-3153.
15. Guo, F. H.; Clift, M. D.; Thomson, R. J., Eur. J. Org. Chem. 2012,
4881-4896.
16. N-Methylpyrrolidine (33%), N(n-Pr)3 (40%), DIPEA (71%), and
DABCO (21%) provide lower yields under the standard conditions.
17. Ishiyama, T.; Murata, M.; Miyaura, N., J. Org. Chem. 1995, 60, 7508-
7510.
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
We have reported a new oxidative coupling method for
the mild and efficient construction of sp2–sp3 carbon–carbon
bonds.19 This decarboxylative α-arylation of malonic half
esters and amides proceeds at room temperature, in air, un-
der mildly basic conditions, and employs both a simple cop-
per catalyst and stable aryl boronic esters. In contrast with
existing enolate arylation chemistry, this oxidative strategy is
compatible with protic and electrophilic functional groups,
facilitating applications in late-stage functionalization. We
have demonstrated that biomimetic decarboxylative trapping
of malonate derivatives can provide new routes to the core of
drug molecules and should find immediate use in the prepa-
ration of aryl acetates and related derivatives in the context
of functional molecule synthesis.
Supporting Information
Experimental procedures and compound characterization
data. This material is available free of charge via the Internet
at http://pubs.acs.org.
Corresponding Author
rylan.lundgren@ualberta.ca
ACKNOWLEDGMENT
We thank NSERC Canada (DG, RTI, and Engage, CGS-D
fellowship to P.J.M.), the University of Alberta, and SV
ChemBioTech for support. Wenyu Qian (Alberta) is
acknowledged for checking the procedure and preparing 6a’.
REFERENCES
1. (a) Staunton, J.; Weissman, K. J., Nat. Prod. Rep. 2001, 18, 380-416;
(b) Smith, S.; Tsai, S.-C., Nat. Prod. Rep. 2007, 24, 1041-1072.
2. (a) Weaver, J. D.; Recio, A., III; Grenning, A. J.; Tunge, J. A., Chem.
Rev. 2011, 111, 1846-1913; (b) Rodriguez, N.; Goossen, L. J., Chem. Soc.
Rev. 2011, 40, 5030-5048; (c) Nakamura, S., Org. Biomol. Chem. 2014,
12, 394-405; (d) Pan, Y. H.; Tan, C. H., Synthesis 2011, 2044-2053.
3. (a) Lalic, G.; Aloise, A. D.; Shair, M. D., J. Am. Chem. Soc. 2003, 125,
2852-2853; (b) Magdziak, D.; Lalic, G.; Lee, H. M.; Fortner, K. C.; Alo-
ise, A. D.; Shair, M. D., J. Am. Chem. Soc. 2005, 127, 7284-7285; (c)
Blaquiere, N.; Shore, D. G.; Rousseaux, S.; Fagnou, K., J. Org. Chem.
2009, 74, 6190-6198; (d) Walker, M. C.; Thuronyi, B. W.; Charkoudian,
L. K.; Lowry, B.; Khosla, C.; Chang, M. C. Y., Science 2013, 341, 1089-
1094; (e) Saadi, J.; Wennemers, H., Nature Chem. 2016, 8, 276-280; (f)
Behenna, D. C.; Liu, Y. Y.; Yurino, T.; Kim, J.; White, D. E.; Virgil, S.
C.; Stoltz, B. M., Nature Chem. 2012, 4, 130-133; (g) Bae, H. Y.; Sim, J.
18. Ishiyama, T.; Takagi, J.; Hartwig, J. F.; Miyaura, N., Angew. Chem.
Int. Ed. 2002, 41, 3056-3058.
19. Preliminary mechanistic studies are suggestive of a Chan-Evans-Lam
type redox pathway in which C–C bond forming reductive elimination is
followed by decarboxylation. For a detailed mechanistic study of the
Chan-Evans-Lam reaction see King, A. E.; Ryland, B. L.; Brunold, T. C.;
Stahl, S. S., Organometallics 2012, 31, 7948-7957.
ACS Paragon Plus Environment

Page 5 of 5
Journal of the American Chemical Society
1
2
3
4
5
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
ACS Paragon Plus Environment