Catalytic enantioconvergent decarboxylative allylic alkylation of allyl indolenin-3-carboxylates

Article abstract of DOI:10.1002/ejoc.201300515

A catalytic enantioconvergent process has been developed for the conversion of racemic allyl indolenin-3-carboxylates into enantiomerically enriched C3-quaternary indolenines. A Pd-catalyzed decarboxylative allylic alkylation reaction was employed for both stereoablation of the racemic allyl indolenin-3-carboxylates and enantioselective formation of the quaternary carbon center. The enantioconvergent conversion of racemic allyl indolenin-3- carboxylates into enantiomerically enriched C3-quaternary indolenines is reported. A Pd-catalyzed decarboxylative allylic alkylation reaction is employed for both stereoablation and enantioselective formation of the quaternary carbon center. Copyright

Full text of DOI:10.1002/ejoc.201300515

Job/Unit: O30515
/KAP1
Date: 15-05-13 18:10:39
Pages: 6
SHORT COMMUNICATION
Enantioconvergent Transformations
The enantioconvergent conversion of ra-
cemic allyl indolenin-3-carboxylates into
enantiomerically enriched C3-quaternary
indolenines is reported. A Pd-catalyzed de-
carboxylative allylic alkylation reaction is
employed for both stereoablation and en-
antioselective formation of the quaternary
carbon center.
T. M. Kaiser, J. Yang* ...................... 1–6
Catalytic
Enantioconvergent
Decarb-
oxylative Allylic Alkylation of Allyl Indol-
enin-3-carboxylates
Keywords: Enantioconvergent reactions /
Palladium / Chirality / Allylic compounds /
Boranes
0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1

Job/Unit: O30515
/KAP1
Date: 15-05-13 18:10:39
Pages: 6
T. M. Kaiser, J. Yang
SHORT COMMUNICATION
DOI: 10.1002/ejoc.201300515
Catalytic Enantioconvergent Decarboxylative Allylic Alkylation of Allyl
Indolenin-3-carboxylates
Thomas M. Kaiser[a] and Jiong Yang*[a]
Keywords: Enantioconvergent reactions / Palladium / Chirality / Allylic compounds / Boranes
A catalytic enantioconvergent process has been developed
for the conversion of racemic allyl indolenin-3-carboxylates
into enantiomerically enriched C3-quaternary indolenines. A
Pd-catalyzed decarboxylative allylic alkylation reaction was
employed for both stereoablation of the racemic allyl ind-
olenin-3-carboxylates and enantioselective formation of the
quaternary carbon center.
tramolecular C3 alkylation of indoles to give spiroind-
olenines and on cascade reactions involving C3 alkylation
accompanied by spontaneous cyclization of the indolenine
intermediates to give the thermodynamically favorable pyr-
roloindolines or hexahydrocarbazoles,[7] dearomatizing all-
ylic alkylation of 3-substituted indoles to give C3-quater-
nary indolenines is challenging and has only been rarely
explored until recently.[8] Herein, we report the results of
our study, which culminated in an enantioconvergent pro-
cess for the synthesis of C3-quaternary indolenines through
deracemization of the quaternary stereocenter of allyl ind-
olenin-3-carboxylates.
Introduction
Enantioconvergent reactions are remarkable processes in
which enantiomerically enriched products are produced
from racemic starting materials through dynamic kinetic
resolution (DKR),[1] dynamic kinetic asymmetric transfor-
mation (DYKAT),[2] or direct enantioconvergent transfor-
mation (DET).[3] These reactions allow enantioselective
synthesis of useful chiral building blocks if the racemic
starting materials are readily available. We recently devel-
oped approaches for the rapid synthesis of diversely substi-
tuted C3-quaternary indolenin-3-carboxylates.[4] Although
our efforts for developing enantioselective variants of these
reactions have been unsuccessful, we identified that the ra-
cemic compounds underwent facile decarboxylation upon
saponification of their C3 esters to give the corresponding
3-substituted indoles. On the basis of these preliminary fin-
dings, we envisioned a DYKAT process through catalytic
enantioselective decarboxylative allylic alkylation to convert
these readily available allyl indolenin-3-carboxylates into
enantiomerically enriched C3-quaternary indolenines
(Scheme 1), which are valuable building blocks for the syn-
thesis of complex indole alkaloids.[5] Significant challenges
were anticipated for such a process, as a myriad of side
reactions could potentially derail the envisioned process,
such as the difficulty of the C3-quaternary allyl ester to
undergo oxidative addition with Pd0 and the ensuing de-
carboxylation reaction, inadequate π nucleophilicity of the
initially formed indoles for reaction with the π–allyl com-
plexes to generate the C3 quaternary center in the dearoma-
tizing process,[6] competing N1- and C2-allylation reactions,
and so on. Further, despite a number of reports on the in-
Scheme 1. Enantioconvergent decarboxylative allylic alkylation of
allyl indolenin-3-carboxylates.
Results and Discussion
Our foray into developing such a process started by test-
ing its feasibility by using common Pd catalyzed allylic alk-
ylation systems with 1a as a model substrate (Table 1).[9]
Following the precedent of Rawal and co-workers for the
intermolecular decarboxylative allylic alkylation of in-
doles,[8b] we treated 1a with Pd2(dba)3/(2-furyl)3P (dba =
dibenzylideneacetone) in CH2Cl2. Although decarboxyl-
ation product 3a was isolated as the major product (56%
yield), we were pleased to find that desired 3-allyl-3-alkyl-
[a] Department of Chemistry, Texas A&M University,
College Station, Texas 77843-3255, USA
E-mail: yang@mail.chem.tamu.edu
Homepage: http://www.chem.tamu.edu/rgroup/yang
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300515.
2
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O30515
/KAP1
Date: 15-05-13 18:10:39
Pages: 6
Catalytic Enantioconvergent Decarboxylative Allylic Alkylation
Table 1. Optimization of the reaction conditions.[a]
Entry
1
L
Additive
Solvent
T [°C]
% Yield 2/3
% ee 2[b]
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
(2-furyl)3P
(2-furyl)3P
(2-furyl)3P
none
AcOH
MeOH
CuI
none
CuI
Et3B
C12H17BO2
hexyl-9-BBN
hexyl-9-BBN
hexyl-9-BBN
hexyl-9-BBN
hexyl-9-BBN
hexyl-9-BBN
hexyl-9-BBN
hexyl-9-BBN
Ph3B
CH2Cl2
23
23
23
23
23
23
23
23
0
0
0
0
0
34:56
0:85
30:70
92:0
0:37
0:0
n.a.
n.a.
n.a.
n.a.
n.a.
n.a.
49
n.a.
55
56
64
48
65
n.d.
57
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
toluene
(CHCl2)2
dioxane
THF
THF
THF
THF
THF
THF
THF
(2-furyl)3P
L1
L1
L1
62:16
0:21
L1
9
L1
44:20
48:14
44:23
48:19
43:20
35:12
44:21
0:13
10
11
12
13
14
15
16
17
18
19[c]
L1
L1
L1
L1
L1
–20
0
0
0
0
L2
L3
n.d.
n.d.
n.d.
77
L1
33:14
0:0
80:0
L1
(F6C5)3B
hexyl-9-BBN
L1
0
[a] Unless noted otherwise, the following conditions were used for the reactions: Pd2(dba)3 (2.5 mol-%), ligand (7.5 mol-%), and R3B
(0.5 equiv.) when applicable. [b] n.a.: not applicable, n.d.: not determined. [c] Pd2(dba)3 (2.3 mol-%), L1 (11.25 mol-%), and hexyl-9-BBN
(1.05 equiv.).
indolenine 2a was also formed (34% yield; Table 1, entry 1). of indoles,[8a,11] we tested triethylborane (0.5 equiv.) as the
The efficiency of the reaction could be fine-tuned with addi- reaction additive. Indeed, this led to the formation of 2b in
tives. For example, whereas only decarboxylation product 62% yield with 49%ee (Table 1, entry 7). Encouraged by
3a was formed when HOAc was used as an additive this result, we also tested n-hexylcatecholborane and n-
(Table 1, entry 2), the reaction proceeded essentially quanti- hexyl-9-BBN (BBN = borabicyclo[3.3.1]nonane) for their
tatively to convert 1a into 2a and 3a in 30 and 70% yield, effects. Whereas only decarboxylation product 3b was
respectively, in the presence of MeOH (Table 1, entry 3). formed when n-hexylcatecholborane was used (Table 1, en-
The highest reaction efficiency was achieved when CuI was try 8), the addition of hexyl-9-BBN led to the formation of
used as the additive; 3a was formed in 92% yield and only 2b in 44% yield with 55%ee (Table 1, entry 9). Subsequent
a trace amount of 3b was generated (Table 1, entry 4).[10]
testing with Ph3B and (C6F5)3B for reaction additive
Having established the feasibility of the reaction, we showed that they were not as effective (Table 1, entries 17
turned to chiral catalytic systems to develop an enantiocon- and 18). Further screening of the reaction conditions re-
vergent variant of the transformation. Initial experiments vealed THF to be the solvent of choice at 0 °C (Table 1,
with the use of Pd2(dba)3 and Trost ligand (R,R)-L1 and 1b entries 13, 15, and 16) whereas low conversion was observed
as the substrate proved to be ineffective, as only decarboxyl- when the reaction was conducted at –20 °C (Table 1, en-
ation product 3b was formed, together with the recovered try 14). Trost ligand L2 also catalyzed this Pd-catalyzed en-
starting material (Table 1, entry 5). Surprisingly, the ad- antioconvergent transformation with slightly reduced
dition of CuI as the additive to the reaction led to complete enantioselectivity (Table 1, entry 15). Somewhat surpris-
recovery of the starting material (Table 1, entry 6). Being ingly, other common catalytic systems, such as Pd2(dba)3–
aware of the positive influence of trialkylboranes in Pd-cat- L3 (Table 1, entry 16) and [Ir(cod)Cl]2–L4 (not shown, cod
alyzed intermolecular allylation and benzylation reactions = 1,5-cyclooctadiene), were found to be ineffective. Finally,
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3

Job/Unit: O30515
/KAP1
Date: 15-05-13 18:10:39
Pages: 6
T. M. Kaiser, J. Yang
SHORT COMMUNICATION
we were pleased to find that formation of decarboxylation Table 2. Substrate scope.
product 3b could be suppressed if a stoichiometric amount
of hexyl-9-BBN (1.05 equiv.) was used, and the enantio-
selectivity could be improved to 77%ee if 11 mol-% of L1
was employed (Table 1, entry 19).[12] The absolute stereo-
chemical configuration of 2b was assigned as shown by
comparing its optical rotation with that of the literature
value.[8a]
This enantioconvergent process appeared to be general
and gave good yields for most of the substrates that we
tested. Substitution at the C5 position was well tolerated.
For example, 5-methoxy- and 5-methyl-substituted sub-
strates underwent the decarboxylative allylic alkylation to
give the corresponding products (i.e., 2c and 2d) in high
yields (82 and 94%) with ee values (80 and 76%) similar to
that of 2b (Table 2). An electron-withdrawing chloride at
the C5 position was also compatible even though the yield
(61%) and ee (64%) of the product (i.e., 2e) were somewhat
reduced. Allyl indolenine-3-carboxylates with 3-allyl or 3-
benzyl substitution gave uniformly high yields (Ͼ90%)
upon decarboxylative allylic alkylation even though varying
ee values were observed. For example, whereas prenyl-sub-
stituted indolenine 2g was formed in 60%ee upon decarb-
oxylative allylic alkylation, crotyl-substituted indolenine 2f
was formed with slightly lower enantioselectivity of 54%ee.
Similarly, various benzyl-substituted C3-quaternary in-
dolenines (i.e., 2h to 2k) were obtained with 59–73%ee
upon reaction of the corresponding allyl indolenin-3-carb-
oxylates. We were pleased to observe that 2l was formed
in 62% yield with 74%ee from the corresponding crotyl
indolenin-3-carboxylate. An elevated reaction temperature
(40 °C) was necessary for the reaction of the less-reactive
methallyl ester to give 2m in 76% yield with a low ee of
29%. Only racemic indolenine 2n was formed in 52% yield
when the corresponding prenyl ester was subjected to the
reaction at elevated temperature. Methyl substitution at the
C6 and C7 positions was found to be incompatible with the
[a] Reaction carried out at room temperature. [b] Reaction carried
out at 40–45 °C. [c] Yield of the decarboxylation product.
reaction, as only the decarboxylation products (i.e., 3a and
3o) were formed.
As part of the study and to gain insight into the mechan-
istic details of the reaction, a crossover experiment was car-
ried out in which a 1:1 mixture of 1h/1l was subjected to
the decarboxylative allylic alkylation reaction conditions
(Scheme 2). Only 2h and 2l were formed, and this indicates
that the reactive species that were formed from each of the
substrates remained closely associated during the process
and recombined to give the products.
Our experimental findings suggest that the trialkylborane
participates in the reaction both as a Lewis acid to facilitate
decarboxylative elimination of the C3 esters and as part of
a strongly π-nucleophilic N-indolyltrialkylborate species for
dearomatizing C3-allylic alkylation to form the quaternary
Scheme 2. A crossover experiment.
carbon center. A proposed reaction mechanism that ac- carboxylate to give tightly associated ion pair B.[14] Subse-
counts for these effects is depicted in Scheme 3.[13] First, N– quent C3 allylation of the solvent-caged N-indolyltrialkyl-
B coordination of indolenine (1) and trialkylborane forms borate and the chiral cationic Pd–π–allyl complex gives C,
electron-deficient 3H-indolium intermediate A. This leads which dissociates to form enantiomerically enriched C3-
to activation of the allyl ester towards oxidative addition quaternary indolenine 2. Formation of the electron-rich N-
of Pd0 and facilitates decarboxylation of the resulting C3 indolyltrialkylborate species leads to increased π-nucleo-
4
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O30515
/KAP1
Date: 15-05-13 18:10:39
Pages: 6
Catalytic Enantioconvergent Decarboxylative Allylic Alkylation
10 min at room temperature. The solution was cooled to 0 °C and
cannulated to a flask containing (Ϯ)-allyl indolenin-3-carboxylate
(0.19 mmol) under a nitrogen atmosphere at 0 °C. The reaction was
stirred for 2 min at 0 °C and the aforementioned borane solution
(0.8 mL) was added. The reaction was sealed with Parafilm® and
stirred at 0 °C for 16 h.
philicity for the dearomatizing C3 allylation reactions. Con-
sistent with this hypothesis, only the decarboxylation prod-
uct (i.e., 3a) was formed when 1a was subjected to the reac-
tion conditions, likely due to impeded N–B coordination as
a result of 7-Me substitution, which prevented formation of
the nucleophilic N-indolyltrialkylborate species.[15]
Workup Procedure A: The reaction was quenched with the addition
of a saturated aqueous solution of NaHCO3 (3 mL), and the mix-
ture was vigorously stirred for 2 h. The mixture was then diluted
with water (5 mL) and extracted with EtOAc (3ϫ15 mL). The
combined organic layer was dried (Na2SO4), filtered, and concen-
trated.
Workup Procedure B: The reaction was quenched with the addition
of 2 n NaOH (2 mL) and diluted with EtOAc (3 mL). The mixture
was then vigorously stirred for 2 h before it was diluted with water
(5 mL) and extracted with EtOAc (3ϫ15 mL). The combined or-
ganic layer was dried (Na2SO4), filtered, and concentrated.
Workup Procedure C: Ethanolamine (35 μL, 0.57 mmol) was added
to the reaction mixture, and the solution was stirred vigorously for
2 h. The resulting mixture was filtered, and the filtrate was washed
with EtOAc (15 mL). The combined organic phase was washed
with a saturated aqueous solution of Na2CO3 (5 mL) and brine
(5 mL) before it was dried with Na2SO4, filtered, and concentrated.
Supporting Information (see footnote on the first page of this arti-
cle): Detailed experimental procedures and characterization data,
including 1H NMR, 13C NMR, and HRMS spectra and chiral
HPLC traces for new compounds.
Scheme 3. A proposed reaction mechanism.
Conclusions
Acknowledgments
We developed an enantioconvergent process for the con-
version of racemic allyl indolenin-3-carboxylates into enan-
tiomerically enriched C3-quaternary indolenines. This
transformation employs a Pd-catalyzed decarboxylative
allylic alkylation for both stereoablation and dearomatizing
enantioselective alkylation to give the C3 quaternary center.
Both the nucleophile and the electrophile are derived from
the allyl indolenin-3-carboxylate under Pd catalysis. The tri-
alkylborane was found to be an essential additive to the
reaction. We attribute this trialkylborane effect to its ability
to participate both as a Lewis acid to facilitate the decarb-
oxylation process and as part of a strongly π-nucleophilic
N-indolylborate species for dearomatizing the allylic alkyl-
ation to form the C3 quaternary centers. Studies to further
explore the synthetic utility of these borate species are in
progress.
This work was supported in part by the Robert A. Welch Founda-
tion (A-1700) and the National Science Foundation (NSF) (grant
number CHE-1150606).
[1] For theoretical classification, see: a) K. Faber, Eur. J. Org.
Chem. 2001, 5004–5010; b) J. Steinreiber, K. Faber, H. Griengl,
Chem. Eur. J. 2008, 14, 8060–8072; for pioneering work on
DKR, see: c) R. Noyori, M. Tokunaga, M. Kitamura, Bull.
Chem. Soc. Jpn. 1995, 68, 36–55 and references cited therein;
for some reviews, see: d) F. F. Huerta, A. B. E. Minidis, J.-E.
Bäckvall, Chem. Soc. Rev. 2001, 30, 321–331; e) B. M. Trost,
D. R. Fandrick, Aldrichim. Acta 2007, 40, 59–72; f) H. Pelliss-
ier, Tetrahedron 2008, 64, 1563–1601.
[2] DYKAT was introduced by Trost and co-workers, see: a) B. M.
Trost, F. D. Toste, J. Am. Chem. Soc. 1999, 121, 3543–3544; b)
B. M. Trost, R. C. Bunt, R. C. Lemoine, T. L. Calkins, J. Am.
Chem. Soc. 2000, 122, 5968–5976; for some recent examples of
DYKAT involving catalytic decarboxylative allylic alkylation,
see: c) J. T. Mohr, D. C. Behenna, A. M. Harned, B. M. Stoltz,
Angew. Chem. 2005, 117, 7084–7087; Angew. Chem. Int. Ed.
2005, 44, 6924–6927; d) D. C. Behenna, Y. Liu, T. Yurino, J.
Kim, D. E. White, S. C. Virgil, B. M. Stoltz, Nature Chem.
2012, 4, 130–133; e) V. Franckevicius, J. D. Cuthbertson, M.
Pickworth, D. S. Pugh, R. J. K. Taylor, Org. Lett. 2011, 13,
4264–4267; for some recent examples, see: f) M. Luparia, M. T.
Oliveira, D. Audisio, F. Frébault, R. Goddard, N. Maulide,
Angew. Chem. 2011, 123, 12840–12844; Angew. Chem. Int. Ed.
2011, 50, 12631–12635; g) D. Audisio, M. Luparia, M. T. Ol-
iveira, D. Klütt, N. Maulide, Angew. Chem. 2012, 124, 7426–
7429; Angew. Chem. Int. Ed. 2012, 51, 7314–7317.
Experimental Section
Borane Generation: A flame-dried, 3 mL conical flask was placed
under an atmosphere of nitrogen and charged with a solution of 9-
BBN (0.5 m in THF, 0.63 mL, 0.315 mmol). This solution was then
diluted with THF (0.63 mL) and 1-hexene (93 μL, 0.75 mmol) was
added. The reaction was stirred at room temperature for 4 h.
Enantioconvergent Decarboxylative Allylic Alkylation: A flame-
dried, 10 mL flask was charged with Pd2(dba)3 (4.0 mg,
0.004 mmol) and (R,R)-ANDEN-phenyl Trost ligand L1 (17.4 mg,
0.0214 mmol). The contents of the flask were placed under a nitro-
gen atmosphere and THF (4.4 mL) was added and stirred for
[3] For enantioconvergent processes involving DET, see: a) H. Ito,
S. Kunii, M. Sawamura, Nature Chem. 2010, 2, 972–976; b) M.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O30515
/KAP1
Date: 15-05-13 18:10:39
Pages: 6
T. M. Kaiser, J. Yang
SHORT COMMUNICATION
Chen, W. R. Roush, J. Am. Chem. Soc. 2011, 133, 5744–5747;
c) J.-B. Langlois, D. Emery, J. Mareda, A. Alexakis, Chem. Sci.
2012, 3, 1062–1064.
123, 8255–8259; Angew. Chem. Int. Ed. 2011, 50, 8105–8109;
m) S. B. Jones, B. Simmons, D. W. C. MacMillan, J. Am. Chem.
Soc. 2009, 131, 13606–13607; n) Y. Liu, W. Xu, X. Wang, Org.
Lett. 2010, 12, 1448–1451; o) Z. Zhang, J. C. Antilla, Angew.
Chem. 2012, 124, 11948–11952; Angew. Chem. Int. Ed. 2012,
51, 11778–11782.
[4] a) C. B. Huehls, T. Hood, J. Yang, Angew. Chem. 2012, 124,
5200–5203; Angew. Chem. Int. Ed. 2012, 51, 5110–5113; b) A.
Lin, J. Yang, M. Hashim, Org. Lett. 2013, 15, 1950–1953.
[5] For examples, see: a) R. Robinson, H. Suginome, J. Chem. Soc.
1932, 298–304; b) R. B. Woodward, M. P. Cava, W. D. Ollis, A.
Hunger, H. U. Daeniker, K. Schenker, J. Am. Chem. Soc. 1954,
76, 4749–4751; c) G. Stork, J. E. Dolfini, J. Am. Chem. Soc.
1963, 85, 2872–2873; d) F. He, Y. Bo, J. D. Altom, E. J. Corey,
J. Am. Chem. Soc. 1999, 121, 6771–6772; e) S. A. Kozmin, T.
Iwama, Y. Huang, V. H. Rawal, J. Am. Chem. Soc. 2002, 124,
4628–4641.
[8] a) B. M. Trost, J. Quancard, J. Am. Chem. Soc. 2006, 128, 6314;
b) N. Kagawa, J. P. Malerich, V. H. Rawal, Org. Lett. 2008, 10,
2381–2384; for reports during preparation of our manuscript,
see: c) Y. Liu, H. Du, Org. Lett. 2013, 15, 740–743; d) J. Chen,
M. J. Cook, Org. Lett. 2013, 15, 1088–1091; e) T. D. Montgom-
ery, Y. Zhu, N. Kagawa, V. H. Rawal, Org. Lett. 2013, 15, 1140–
1143. So far, the C3-quaternary indolenines were obtained in
90%ee in only two cases (see ref.[8a]).
[6] For reviews of dearomatization strategies in natural product [9] For some reviews, see: a) J. D. Weaver, A. Recio III, A. J. Gren-
Synthesis see: a) S. P. Roche, J. A. Porco, Angew. Chem. 2011,
123, 4154–4179; Angew. Chem. Int. Ed. 2011, 50, 4068–4093;
b) C.-X. Zhuo, W. Zhang, S.-L. You, Angew. Chem. 2012, 124,
12834–12858; Angew. Chem. Int. Ed. 2012, 51, 12662–12686.
[7] a) Q.-F. Wu, C. Zheng, S.-L. You, Angew. Chem. 2012, 124,
1712–1715; Angew. Chem. Int. Ed. 2012, 51, 1680–1683; b) Q.
Cai, C. Zheng, J.-W. Zhang, S.-L. You, Angew. Chem. 2011,
123, 8824–8828; Angew. Chem. Int. Ed. 2011, 50, 8665–8669;
c) Q.-F. Wu, H. He, W.-B. Liu, S.-L. You, J. Am. Chem. Soc.
ning, J. A. Tunge, Chem. Rev. 2011, 111, 1846–1913; b) Z. Lu,
S. Ma, Angew. Chem. 2008, 120, 264–303; Angew. Chem. Int.
Ed. 2008, 47, 258–297; c) B. M. Trost, M. L. Crawley, Chem.
Rev. 2003, 103, 2921–2944; d) B. M. Trost, D. L. Van Vranken,
Chem. Rev. 1996, 96, 395–422.
[10] The effect of CuI appears to be specific to 1a, as no reaction
was observed when unsubstituted allyl indolenin-3-carboxylate
(1b) was treated under the same reaction conditions.
[11] Y. Zhu, V. H. Rawal, J. Am. Chem. Soc. 2012, 134, 111–114.
2010, 132, 11418–11419; d) K.-J. Wu, L.-X. Dai, S.-L. You, [12] See the Supporting Information for a list of the conditions that
Org. Lett. 2012, 14, 3772–3775; e) S. Zhu, D. W. C. MacMillan,
J. Am. Chem. Soc. 2012, 134, 10815–10818; f) M. E. Kieffer,
K. V. Chuang, S. E. Reisman, Chem. Sci. 2012, 3, 3170–3174;
g) Q. Cai, S.-L. You, Org. Lett. 2012, 14, 3040–3043; h) Q. Cai,
C. Liu, X.-W. Liang, S.-L. You, Org. Lett. 2012, 14, 4588–4590;
i) S. Lucarini, F. Bartoccini, F. Battistoni, G. Diamantini, G.
Piersanti, M. Righi, G. Spadoni, Org. Lett. 2010, 12, 3844–
3847; j) L. M. Repka, J. Ni, S. E. Reisman, J. Am. Chem. Soc.
2010, 132, 14418–14419; k) J. F. Austin, S.-G. Kim, G. J. Sinz,
W.-J. Xiao, D. W. C. MacMillan, Proc. Natl. Acad. Sci. USA
2004, 101, 5482–5487; l) O. Lozano, G. Blessley, T. Marti-
nez del Campo, A. L. Thompson, G. T. Giuffredi, M. Bettati,
M. Walker, R. Borman, V. Gouverneur, Angew. Chem. 2011,
were tested.
[13] Related trialkylborane effects have been known. However, to
the best of our knowledge, the nature of such effects has not
been clearly defined. See ref.[7a,10] and: M. Kimura, Y. Horino,
R. Mukai, S. Tanaka, Y. Tamaru, J. Am. Chem. Soc. 2001, 123,
10401–10402.
[14] An alternative pathway for Lewis acidic activation through O–
B coordination of the trialkylborane and the carbonyl group of
2 is less likely because of the sterically congested environment.
[15] It is unclear why C6-methyl-substituted indolenine (i.e., 2o)
also failed to form under the reaction conditions.
Received: April 9, 2013
Published Online: ᭿
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0