Enantioselective C2-Alkylation of Indoles through a Redox-Relay Heck Reaction of 2-Indole Triflates

Article abstract of DOI:10.1002/chem.201805416

A palladium-catalyzed enantioselective redox-relay Heck reaction of 2-indole triflates and disubstituted alkenes is reported. This process combines readily available indole triflates with a variety of alkenes to afford a range of indole derivatives bearing a stereocenter adjacent to C2. Enantioselectivity is achieved through use of a simple pyridine-oxazoline ligand. Tuning the electronics of the indole, through judicious choice of N-protecting group, is required to ensure selective β-hydride elimination away from the indole core. Utility of this method is highlighted in a modular formal synthesis of an S1P₁ agonist precursor developed by Merck.

Full text of DOI:10.1002/chem.201805416

A Journal of
Accepted Article
Title: Enantioselective C2-alkylation of indoles via a redox-relay Heck
reaction of 2-indole triflates
Authors: Nicholas Race, Qianjia Yuan, and Matthew S. Sigman
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201805416
Link to VoR: http://dx.doi.org/10.1002/chem.201805416
Supported by

10.1002/chem.201805416
Chemistry - A European Journal
COMMUNICATION
Enantioselective C2-alkylation of indoles via a redox-relay Heck
reaction of 2-indole triflates
Nicholas J. Race,# Qianjia Yuan,# and Matthew S. Sigman*[a]
Abstract: A palladium-catalyzed enantioselective redox-relay Heck
reaction of 2-indole triflates and disubstituted alkenes is reported. This
process combines readily-available indole triflates with a variety of
alkenes to afford a range of indole derivatives bearing a stereocenter
adjacent to C2. Enantioselectivity is achieved through use of a simple
pyridine-oxazoline ligand. Tuning the electronics of the indole, through
judicious choice of N-protecting group, is required to ensure selective
-hydride elimination away from the indole core. Utility of this method
is highlighted in a modular formal synthesis of an S1P1 agonist
precursor developed by Merck.
in related Heck reactions,10d-f these electrophiles were selected
for investigation and 2) the nature of the indole nitrogen
substituent was deemed important with an electron withdrawing
group possibly required to dissuade the Pd from migrating
towards the indole (Scheme 1D).10d This was hypothesized on the
basis of previous mechanistic work wherein the Pd-catalyst has
the propensity to migrate toward more electron rich features of the
alkyl chain. Indeed, use of disubstituted alkenols in the
dehydrogenative arylation with indole did not lead to the desired
relay product as a consequence of the electron-rich indole
nucleus (Scheme 1C). Specifically, intermediate D underwent
selective -hydride elimination of R2 (R2 = H) and subsequent
reinsertion of the Pd(II)-hydride afforded Pd(II)-alkyl E, which
decomposed via expulsion of Pd(0) as promoted by the electrons
on the indole nitrogen.
Indole is a privileged scaffold in a wide variety of research
areas, including natural product synthesis, pharmaceuticals,
agrochemicals and material science.1 As a result, numerous
synthetic methods have been developed for the synthesis and
functionalization
of
indole.
Catalytic,
enantioselective
A. C3 vs C2 indole functionalization
functionalization of the indole core represents an intensive area
of research, with most methods exploiting the inherent
nucleophilicity at the C3 position for enantioselective
Friedel-Crafts-like chemistry (Scheme 1A).2 For example, we
R2
R1
*
R3
enantioselective
C3 functionalization
enantioselective
C2 functionalization
R1
R2
*
R3
N
N
N
established
less developed
R
R
R
recently reported
a
palladium-catalyzed dehydrogenative
B. Indoles bearing a stereocenter adjacent to C2 position
relay-Heck arylation of indole derivative A and trisubstituted
alkenols to afford aldehydes of type B (Scheme 1C).3 Given that
palladation of indole is proposed to occur in a Friedel-Crafts-like
manner (A → C, Scheme 1C),4 functionalization of the C3 position
is observed exclusively.
In contrast, methods to enantioselectively functionalize the
indole C2 position are much less developed.5 In fact,
incorporation of a substituent at indole C3 is typically required to
O
O
O
HO
N
N
CO2Me
N
N
H
N
H
Me
H
Bn
S1P1 precursor
(Merck)
anti-malarial
lead compound
(R)-deplancheine
C. C3-Functionalization via dehydrogenative redox-relay Heck reaction of indole
R2
R1
Pd(II)/L*
oxidant
O
promote
electrophilic
substitution
at
C2.
Therefore,
R2
OH
+
prefunctionalization of the indole is a strategy used to ensure a
site-selective reaction. As an example, Macmillan reported a
singular case of a conjugate addition reaction of C2-bearing
indole potassium trifluoroborate salts to enals using secondary
amine catalysis.6 Given that many natural products and
pharmaceutical relevant core structures contain a stereocenter
adjacent to the C2 position (Scheme 1B),7-9 we considered
strategies to apply a redox-relay Heck type reaction10 using an
appropriately functionalized indole starting material for the
purposes of enantioselective indole C2 functionalization. By
coupling this starting material with a diverse selection of alkene
coupling partners, we would be able to streamline access to a
wide variety of enantioenriched molecular scaffolds.
R1/R2
H
R1
N
N
A
B
Alkyl
Alkyl
PdII
Pd(II)
R2
R1
Pd(II)
Pd(II)
R1/R2 ≠ H
R1
OH
OH
R2 = H
N
N
N
C
D
unproductive
E
Alkyl
Alkyl
Alkyl
b-hydride elimination
D. This work: Enantioselective indole C2 functionalization
Ha
Hb
Pd(II)
Tf2O
base
O
OH
N
b-H of Ha
R = alkyl?
R3
undesired
N
R
R
commercial or
one step
Two design elements were considered to accomplish such a
reaction: 1) as indole derived triflates are readily accessible from
simple oxindole starting materials and the corresponding alkenyl
triflates have been demonstrated as excellent coupling partners
Pd(II) Hb
Pd(II)
Ha
OTf
N
OH
N
R
+
R3
N
R
H
R
OH
R3
Hb
Ha
Pd(II)
OH
b-H of Hb
R = EWG?
*
O
[a]
Nicholas J. Race,# Qianjia Yuan,# Matthew S. Sigman*
# denotes equal contribution
Department of Chemistry, University of Utah
315 S 1400 E, Salt Lake City, Utah, 84112
E-mail: matt
R3
N
R3
N
tune R to control
b-H elimination?
R
R
Scheme 1 Catalytic site-selective functionalization of the indole nucleus
This article is protected by copyright. All rights reserved.

10.1002/chem.201805416
Chemistry - A European Journal
COMMUNICATION
On the basis of the design principles described above, a unknown. Use of benzylether-substituted allylic alcohol 13
series of four indole triflates (1-4a) were synthesized with different afforded the desired product 14 in modest yield but excellent
substituents on the indole nitrogen. These substrates were enantioselectivity. Racemic secondary allylic alcohol 15 afforded
evaluated with cis-3-hexen-1-ol (5) under previously reported the corresponding ketone 16 in good yield and enantioselectivity.
conditions reported for alkenyl triflates, which use a Pd(0) The yield of ketone 16 in this reaction is >50%, which suggests
precatalyst and a chiral pyridine-oxazoline ligand (Table 1).10d,11 the stereocenter formed in the product is under catalyst control
No desired reaction was observed with either methyl-, phenyl- or and this reaction is not a kinetic resolution. Finally, we explored
acetyl-substituted indole triflate 1-3 due to decomposition of the the use of an allylic alcohol bearing a primary tosyl-protected
starting materials under the reaction conditions (Entries 1–3). The alcohol (17). Under our reaction conditions, the (formal) alkylation
desired reaction was observed with ethyl carbamate-protected occurs selectively between the indole C2 and the alkene carbon
indole triflate 4 wherein aldehyde 6 was isolated in 19% yield and distal to the primary unprotected alcohol to give 18 in good yield
95:5 er (Entry 4). Addition of two equivalents of alkenol 5 and enantioselectivity. The resulting tosylate and aldehyde
increased the yield to 28% (Entry 5). Given that the Heck reaction provide useful functional groups for further product manipulation.
OH
OH
generates an equivalent of TfOH every catalyst turnover, we
hypothesized that buildup of acid could be problematic, including
decomposition of the starting material through carbamate
deprotection. To improve the yield, a variety of basic additives
were examined in the reaction including K2CO3,
3,5-di-tert-butyl-4-methypyridine, and Ca(OH)2 (Entries 6-8).10f
Addition of one equivalent of Ca(OH)2 improved the yield of
aldehyde 6 to 47%, with no loss in enantioselectivity. The yield of
6 was improved further to 55% by increasing the catalyst loading
to 5 mol % (Entry 9).
O
OH
H
11
HO
R
O
R = Me (7)
R = Cy (8)
N
N
R
CO2Et
12, 86% yield
CO2Et
9, R = Me,
72% yield, 94:6 era
10, R = Cy,
70% yield, 95:5 era
O
OTf
1.8:1 dr
92.5:7.5 erc
N
CO2Et
4
O
Me
N
N
Me
OH
OH
Me
OBn
CO2Et
CO2Et
Me
16, 67% yield
96.5:3.5 er
14, 39% yield
96:4 era,b
2
BnO
O
Pd2(dba)3· CHCl3
13
(+/-)-15
(4 mol %)
OTf
OH
+
N
O
N
R
Me
F3
C
Me
O
R
N
N
OH
standard
PyrOx (10 mol %)t-Bu
3 Å MS, DMF, rt
1-4
(1 equiv)
5
OTf
N
conditions
+
6
(1 equiv)
TsO
57% yield
94.5:5.5 era
N
CO2Et
Resulta
CO2Et
2
3
Entry
R
Additive
OTs
1
2
Me (1)
Ph (2)
-
decomp.
no product
decomp.
17
18
-
a Isolated yield, er determined after NaBH4 reduction to alcohol b Yield of alcohol,
Pd2dba3· CHCl3 (10 mol%), PyrOx (24 mol%) c er determined afer CrO3 oxidation
3
Ac (3)
-
4
CO2Et (4)
CO2Et (4)
CO2Et (4)
CO2Et (4)
CO2Et (4)
CO2Et (4)
-
19% Yield, 95:5 er
28% Yield, 95:5 er
19% Yield, 95:5 er
28% Yield, 95:5 er
47% Yield, 95:5 er
55% Yield, 95:5 er
5b
6b
7b
8b
9b,c
-
Scheme 2. Scope of allylic alcohols
K2CO3 (1 equiv.)
DTBMP (1 equiv.)
Ca(OH)2 (1 equiv.)
Ca(OH)2 (1 equiv.)
Next, we examined the functional group tolerance of the
reaction with respect to substituents on the indole ring using
a Isolated yield, er determined after NaBH4 reduction to alcohol b Two equivalents
of 5 c [Pd] (5 mol %), PyrOx (12 mol %)
homoallylic alcohol
5
(Scheme 3A).13 Functional groups
compatible with this chemistry include chloride (6b), esters (6c),
alkyl ethers and silyl ethers (6d and 6f), boronic esters (6e), and
bromide (6g). It is worth noting that the palladium catalyst initiates
selectively at the indole triflate in the presence of the aryl bromide.
The ability to access enantioenriched secondary alkyl
stereocenters adjacent to the indole C2 position remotely to the
aldehyde functional group is highlighted in Scheme 3B. Primary
and secondary bis-homoallylic alkenols 19 and 21 afforded the
corresponding relay-Heck products 20 and 22 in moderate yield
and enantioselectivity. Accessing these types of enantioenriched
products using conventional approaches, for example, using
alkylation chemistry, would be extremely challenging.
Table 1. Reaction optimization
As the next step, we set out to demonstrate the reaction’s
utility for accessing a wide range of molecular architectures
bearing a secondary stereogenic center  to an indole C2
position. Use of simple allylic alcohols 7 and 8 afforded the
corresponding aldehydes 9 and 10 in 72% (94:6 er) and 70% yield
(95:5 er), respectively (Scheme 2). As highlighted in the
introduction, access to aldehydes bearing a -substituted C2-
indole is possible via iminium ion catalysis.6 We therefore chose
to focus our attention on alkene substrates that provide products
not accessible using these methods. For example, coupling of 4
and diol 1112 afforded lactol 12 in 86% yield, 1.8:1 dr. The
enantiomeric excess for this product (92.5:7.5 er) was measured
after oxidation of the crude lactol to the lactone (see Supporting
Information). To the best of our knowledge, enantioselective
conjugate additions to lactones at the indole C2 position is
This article is protected by copyright. All rights reserved.

10.1002/chem.201805416
Chemistry - A European Journal
COMMUNICATION
A. Functional group tolerance on the Indole
O
standard
conditions
OH
OTf
CO2Et
+
N
N
R
Me
Me
Me
R
CO2Et
4b-g
5
6b-g
O
O
Cl
MeO2C
N
N
Me
Me
CO2Et
CO2Et
6b, 56% Yield
94:6 e.r.a
6c, 52% Yield
93.5:6.5 e.r.a
O
O
O
O
MeO
(pin)B
N
N
Me
Me
CO2Et
CO2Et
6d, 47% Yield
95:5 e.r.a
6e, 45% Yield
93.5:6.5 e.r.a
Br
TBSO
N
N
Me
CO2Et
CO2Et
6f, 52% Yield
95.5:4.5 e.r.a
6g, 51% Yield
95.5:4.5 e.r.a
B. Bis-homoallylic alcohols as coupling partners
OH
O
19
Me
Pd(0)
N
Me
CO2Et
20, 54% yield
92:8 erb
OTf
CO2Et
N
Bn
O
4
OH
Bn
21
4 Me
Pd(0)
N
Me
4
CO2Et
22, 46% yield
92:8 erb
a Isolated yield, er determined after NaBH4 reduction to alcohol b Pd2dba3· CHCl3 (7.5
mol%), PyrOx (20 mol%), triflate (1 equiv, added in two batches), alkenol (3 equiv)
Scheme 4. Indole scope with homoallylic and bis-homoallylic alkenols.
Scheme 3. Indole scope with homoallylic and bis-homoallylic alkenols.
Finally, we wanted to highlight how this indole C2 alkylation
process provides highly modular enantioselective formal access
to tricyclic indole 31, which is a key precursor to an S1P1 agonist
reported by Merck (Scheme 5).9 Initially, Merck developed a route
involving the de novo construction of the indole framework
providing efficient access to the indole core. However, it relies on
the use of traditional chiral auxiliary chemistry to set the absolute
stereochemistry. The relay-Heck reaction conveniently combines
two simple building blocks and sets the stereochemistry during C–
C bond construction providing a modular strategy to such
scaffolds. In the event, indole triflate 4f and alkene 13 are coupled
in moderate yield but excellent enantioselectivity. Processing of
the aldehyde through three steps (oxidation, esterification,
deprotection) afforded indole 30 in 24% yield from triflate 4f (96:4
er). This molecule can be further manipulated to produce S1P1
agonist precursor 31 as established by Merck.9 Optical rotation
comparison of 30 to the literature allowed us to confirm the
absolute stereochemistry of our product to be (S). This
stereochemical outcome is consistent with our previously
reported model for enantioselective induction in relay-Heck
reactions.9 All other compounds were assigned by analogy to 30,
considering that switching the alkene geometry results in the
opposite enantiomer of product being formed.
More recently our group has explored alkenes bearing various
unique functional groups (Scheme 4). As an example, coupling of
indole triflate 4 and enol ether 24 provided aldehyde 23.14 This
reaction affords an enantioenriched secondary ether adjacent to
the indole C2 position, a product not accessible using reported
organocatalytic approaches. Use of commercially-available cis-4-
nonenal 25 afforded ,-unsaturated aldehydes 26a-c in high
yield and good enantioselectivity.15 These products are attractive
because it is well-established that enantioselective intramolecular
cyclizations of related molecules can be promoted by secondary
amines.16 It is also possible to use ene-lactam 27 as a coupling
partner in this chemistry, leading to products 28a-c in excellent
yield and slightly diminished enantioselectivity.17 This reaction
provides rapid and modular access to the core of natural products
and drug candidates (vide supra).
This article is protected by copyright. All rights reserved.

10.1002/chem.201805416
Chemistry - A European Journal
COMMUNICATION
Modular route to S1P1 agonist precursor
2015, 357, 1131; c) P. S. Lee, N. Yoshikai, Org. Lett. 2015, 17, 22;
Intramolecular C2 alkylation: d) M. Bandini, A. Melloni, F. Piccinelli, R.
Sinisi, S. Tommasi, A. Umani-Ronchi, J. Am. Chem. Soc. 2006, 128,
1424; e) M. J. Wanner, R. N. S. van der Haas, K. R. de Cuba, J. H. van
Maarseveen, H. Hiemstra, Angew. Chem. Int. Ed. 2007, 46, 7485; f) N.
V. Sewgobind, M. J. Wanner, S. Ingemann, R. de Gelder, J. H. van
Maarseveen, H. Hiemstra, J. Org. Chem. 2008, 73, 6405; g) J. Franzén,
A. Fisher, Angew. Chem. Int. Ed. 2009, 48, 787; h) Q.-F. Wu, C. Zheng,
S.-L. You, Angew. Chem. Int. Ed. 2012, 51, 1680; i) M. Bandini, A.
Gualandi, M. Monari, A. Romaniello, D. Savoia, M. Tragni, J. Organomet.
Chem. 2011, 696, 338; j) S.-Z. Jiang, X.-Y. Zeng, X. Liang, T. Lei, K. Wei,
Y.-R. Yang, Angew. Chem. Int. Ed. 2016, 55, 4044; k) X. Liang, S.-Z.
Jiang, K. Wei, Y.-R. Yang, J. Am. Chem. Soc. 2016, 138, 2560.
S. Lee, D. W. C. MacMillan, J. Am. Chem. Soc. 2007, 129, 15438.
a) S. M. Allin, C. I. Thomas, K. Doyle, M. R. J. Elsegood J. Org. Chem.
2005, 70, 357; b) S. M. Allin, C. I. Thomas, J. E. Allard, K. Doyle, M. R.
J. Elsegood Eur.–J. Org. Chem. 2005, 4179.
TBSO
OTf
N
O
TBSO
Pd(0)
4f
CO2Et
40-45% Yield
96:4 er
N
OH
29
OBn
CO2Et
BnO
24% yield
(from 4f)
13
96:4 er
TBSO
CO2Me
OBn
HO
steps
ref. 9
CO2Me
N
N
H
30
31, S1P1 agonist precursor
O
O
TBSO
Me
4 steps
[6]
[7]
N
CO2t-Bu
O
+
NH
21% Yield
95:5 er
ref. 9
Bn
Boc
OBn
Merck: de novo indole construction
[8]
[9]
P. Horrocks, S. Fallon, L. Denman, O. Devine, L. J. Duffy, A. Harper, E.-
L. Meredith, S. Hasenkamp, A. Sidaway, D. Monnery, T. R. Phillips, S.
M. Allin, Bioorg. Med. Chem. Lett. 2012, 22, 1770.
Scheme 5. Formal synthesis of an S1P1 agonist
T. O. Schrader, B. R. Johnson, L. Lopez, M. Kasem, T. Gharbaoui, D.
Sengupta, D. Buzard, C. Basmadjian, R. M. Jones, Org. Lett. 2012, 14,
6306.
In conclusion, we have reported an enantioselective C2-
alkylation of indole via a redox-relay Heck reaction of indole triflate
and alkenes. This reaction provides access to a wide selection of
alkylated indole derivatives bearing a stereocenter adjacent to the
C2 position and is tolerant of a range of functional groups. We
highlighted this method by demonstrating its utility for providing
modular formal access to a key tricyclic indole core of a S1P1
agonist precursor. This methodology offers a new disconnection
for synthetic chemists and enables the modular exploration of new
chemical space in the search for new lead drug compounds.
[10] Select examples: a) E. W. Werner, T.-S. Mei, A. J. Burckle, M. S. Sigman,
Science 2012, 338, 1455; b) T.-S. Mei, E. W. Werner, A. J. Burckle, M.
S. Sigman, J. Am. Chem. Soc. 2013, 135, 6830; c) T.-S. Mei, H. H. Patel,
M. S. Sigman, Nature 2014, 508, 340; d) H. H. Patel, M. S. Sigman, J.
Am. Chem. Soc. 2015, 137, 3462; e) H. H. Patel, M. S. Sigman, J. Am.
Chem. Soc. 2016, 138, 14226; f) C. Zhang, B. Tutkowski, R. J. DeLuca, L.
A. Joyce, O. Wiest, M. S. Sigman, Chem. Sci. 2017, 8, 2277; g) Chen,
Z.-M.; Nervig, C. S.; DeLuca, R. J.; Sigman, M. S. Angew. Chem. Int. Ed.
2017, 56, 6651.
[11] G. Yang, W. Zhang, Chem. Soc. Rev. 2018, 47, 1783.
[12] C. C. Oliveira, R. A. Angnes, C. R. D. Correia, J. Org. Chem. 2013, 78,
4373.
[13] 3-Methyl-2-indolyl triflate did not participate in the reaction. In this case
no color change corresponding to oxidative addition of Pd(0) into the
C-OTf bond was observed, presumably due to increased steric hindrance
from the C3 substituent.
Acknowledgements
The work was supported by National Institute of Health (NIGMS
R01GM063540). Q. Y. acknowledges Shanghai Jiao Tong
University for a postdoctoral fellowship. The authors declare no
competing financial interest.
[14] H. H. Patel, M. B. Prater, S. O Squire, M. S. Sigman, J. Am. Chem. Soc.
2018, 140, 5895.
[15] C. Zhang, C. B. Santiago, L. Kou, M. S. Sigman, J. Am. Chem. Soc.
2015, 137, 7290.
[16] a) J.-R. Chen, C.-F. Li, X.-L. An, J.-J. Zhang, X.-Y. Zhu, W.-J. Xiao,
Angew. Chem. Int. Ed. 2008, 47, 2489; b) C.-F. Li, H. Liu, J. Liao, Y.-J.
Cao, X.-P. Liu, W.-J. Xiao, Org. Lett. 2007, 9, 1847.
Keywords: indole • relay-Heck reaction • enantioselective
catalysis • palladium
[17] Q. Yuan, M. S. Sigman, J. Am. Chem. Soc. 2018, 140, 6527.
[1]
[2]
Reviews: a) M. Bandini, A. Eichholzer, Angew. Chem. Int. Ed. 2009, 48,
9608; b) M. Zeng, S.-L. You, Synlett 2010, 1289; c) J.-B. Chen, Y.-X. Jia,
Org. Biomol. Chem. 2017, 15, 3550.
Select examples: a) M. Kokubo, T. Naito, S. Kobayashi, Tetrahedron,
2010, 66, 1111; b) L. Wen, Q. Shen, X. Wan, L. Lu J. Org. Chem. 2011,
76, 2282; c) A. Barakat, M. S. Islam, A. M. A. Al Majid, Z. A. Al-Othman,
Tetrahedron 2013, 69, 5185; d) B. Plancq, M. Lafantaisie, S Companys,
C. Maroun, T. Ollevier, Org. Biomol. Chem. 2013, 11, 7463; e) J.-R. Gao,
H. Wu, B. Xiang, W.B. Yu, L. Han, Y.-X. Jia, J. Am. Chem. Soc. 2013,
135, 2983; f) J.-Q. Weng, Q.-M. Deng, L. Wu, K. Xu, H. Wu, R.-R. Liu,
J.-R. Gao, Y.-X. Jia, Org. Lett. 2014, 16, 776; g) C. Ge, R.-R. Liu, J.-R.
Gao, Y.-X. Jia, Org. Lett. 2016, 18, 3122.
[3]
[4]
C. Zhang, C. B. Santiago, J. M. Crawford, M. S. Sigman, J. Am. Chem.
Soc. 2015, 137, 15668.
a) N. P. Grimster, C. Gauntlett, C. R. A. Godfrey, M. J. Gaunt, Angew.
Chem. Int. Ed. 2005, 44, 3125; b) B. S. Lane, M. A. Brown, D. Sames, J.
Am. Chem. Soc. 2005, 127, 8050.
[5]
Intermolecular C2 alkylation: a) C. Sevov, J. Hartwig, J. Am. Chem. Soc.
2013, 135, 2116; b) T. Shibata, N. Ryu, H. Takano, Adv. Synth. Catal.
This article is protected by copyright. All rights reserved.

10.1002/chem.201805416
Chemistry - A European Journal
COMMUNICATION
COMMUNICATION
Author(s), Corresponding Author(s)*
Page No. – Page No.
Title
O
Br
O
Boc
O
N
OTf
CO2Et
Pd(0)/L*
Me
N
N
R
N
N
Me
Me
4
CO2Et
CO2Et
CO2Et
67% yield
96.5:3.5 er
80% yield
90:10 er
79% yield
93:7 er
This article is protected by copyright. All rights reserved.