Electrophilic Activation of α,β-Unsaturated Amides: Catalytic Asymmetric Vinylogous Conjugate Addition of Unsaturated γ-Butyrolactones

Article abstract of DOI:10.1002/chem.201600740

Although catalytic asymmetric conjugate addition reactions have remarkably advanced over the last two decades, the application of less electrophilic α,β-unsaturated carboxylic acid derivatives in this useful reaction manifold remains challenging. Herein, we report that α,β-unsaturated 7-azaindoline amides act as reactive electrophiles to participate in catalytic diastereo- and enantioselective vinylogous conjugate addition of γ-butyrolactones in the presence of a cooperative catalyst comprising of a soft Lewis acid and a Br?nsted base. Reactions mostly reached completion with as little as 1 mol % of catalyst loading to give the desired conjugate adducts in a highly stereoselective manner.

Full text of DOI:10.1002/chem.201600740

DOI: 10.1002/chem.201600740
Communication
&
Synthetic Methods
Electrophilic Activation of a,b-Unsaturated Amides: Catalytic
Asymmetric Vinylogous Conjugate Addition of Unsaturated
g-Butyrolactones
[
a]
Ming Zhang, Naoya Kumagai,* and Masakatsu Shibasaki*
[
2]
ent in a myriad of natural products; and 2) they are nucleo-
Abstract: Although catalytic asymmetric conjugate addi-
tion reactions have remarkably advanced over the last
two decades, the application of less electrophilic a,b-unsa-
turated carboxylic acid derivatives in this useful reaction
manifold remains challenging. Herein, we report that a,b-
unsaturated 7-azaindoline amides act as reactive electro-
philes to participate in catalytic diastereo- and enantiose-
lective vinylogous conjugate addition of g-butyrolactones
in the presence of a cooperative catalyst comprising of
a soft Lewis acid and a Brønsted base. Reactions mostly
reached completion with as little as 1 mol% of catalyst
loading to give the desired conjugate adducts in a highly
stereoselective manner.
philic at the g-carbon upon deprotonative activation, which
[
3,4]
allows numerous vinylogous additions.
Catalytic asymmetric
vinylogous conjugate addition reactions of g-butenolides to
electron-deficient olefins constitutes an important tool for pro-
[
5–7]
ducing chiral building blocks containing g-butenolide units,
but few studies have provided examples using a,b-unsaturated
carboxylic acid derivatives (Scheme 1a). Zhang et al. disclosed
Conjugate addition reactions are advantageous for assembling
nucleophiles and electron-deficient olefins into larger molecu-
lar architectures. In particular, CÀC bond-forming conjugate ad-
dition reactions play a crucial role in constructing carbon skele-
tons of interest and also have a number of applications in
[1]
modern organic syntheses. In this context, considerable ad-
vances rendered the reaction catalytic and stereoselective to
efficiently afford useful nonracemic building blocks. In general,
the reaction efficiency largely relies on the electrophilic charac-
ter of electron-deficient olefins (electrophiles), and relatively
electrophilic substrates, for example, a,b-unsaturated ketones
Scheme 1. Catalytic asymmetric conjugate addition of butenolides to
a,b-unsaturated carboxylic acid derivatives.
(
enones), a,b-unsaturated aldehydes (enals), and nitroolefins,
are widely utilized. In contrast, less electrophilic a,b-unsaturat-
ed carboxylic acid derivatives are not as well explored due to
their poor electrophilicity, despite the synthetic utility of the
prospective conjugate adducts. This is particularly true when
the nucleophile is catalytically generated in situ, making it
generally less reactive than organometallic reagents, which
remains a major drawback to be addressed.
that a,b-unsaturated imides serve as reactive electrophiles
[
8a]
with thiourea/amine organocatalysts (Scheme 1b).
We re-
ported that a,b-unsaturated thioamides exhibit sufficient elec-
trophilicity in the presence of a soft Lewis acid catalyst to un-
dergo smooth vinylogous addition of g-butenolides, in which
chemoselective activation of the soft Lewis basic thioamide
functionality has a pivotal role in compensating for the low
g-Butenolides have attracted particular attention in the
chemical community, because: 1) g-butenolide units are pres-
[
8b]
electrophilicity.
Although both the reaction efficiency and
stereoselectivity of the above-mentioned protocols are favora-
ble, imides are doubly activated by two carbonyl groups and
thioamides are uncommon functional groups associated with
tedious preparation procedures. Herein, we report an alternative
and more tractable a,b-unsaturated carboxylic acid derivatives,
a,b-unsaturated 7-azaindoline amides, for catalytic asymmetric
vinylogous conjugate addition of g-butenolides (Scheme 1c).
The amides are easily prepared and are bench stable, and the
[
a] Dr. M. Zhang, Dr. N. Kumagai, Prof. Dr. M. Shibasaki
Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki
Shinagawa-ku, Tokyo 141-0021(Japan)
Fax: (+81)3-3441-7589
E-mail: nkumagai@bikaken.or.jp
mshibasa@bikaken.or.jp
Supporting information for this article can be found under http://
dx.doi.org/10.1002/chem.201600740.
Chem. Eur. J. 2016, 22, 5525 – 5529
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ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
observed diastereoselectivity compliments that observed in the
reaction by using a,b-unsaturated imides and thioamides. The
reactions mostly proceed with as little as 1 mol% of catalyst
loading to give high yield and stereoselectivity.
proton (H ) for typical a,b-unsaturated carbonyl compounds,
a
the a-proton (H ) appeared more downfield shifted than the b-
a
proton (H ) in this specific case, strongly suggesting that a hy-
b
drogen-bonding interaction of the a-proton (H ) and a pyridyl
a
[
11]
In our search for alternative a,b-unsaturated carboxylic acid
derivatives that can be catalytically activated, we reasoned
that specific activation by a soft Lewis acid would be key to
enhancing the electrophilicity at the b-carbon. Recently, we
found that a 7-azaindoline amide functionality is a particularly
effective structural motif for chemoselective and deprotonative
nitrogen of the 7-azaindoline unit in E-conformation. Upon
I
the addition of a Cu /(R)-xyl-BINAP complex to 4a, the a-
proton (H ) was significantly shifted upfield, which is ascribed
a
to the breakdown of the above-mentioned hydrogen bonding
and indicative of the chelated Z-conformation. The NOE signals
observed between the a-proton (H ) and aliphatic protons of
a
[
9]
activation. Although the amide inherently prefers the E-con-
formation over the Z-conformation, the Z-conformation be-
comes dominant upon coordination to a soft Lewis acid to
produce a chelated structure. This activated form facilitates
catalytic deprotonation in the presence of a Brønsted base cat-
alyst, rendering catalytic enolization of low-acidic amides by
the 7-azaindoline group are consistent with the Z-conforma-
tion. The Z-conformation was unequivocally determined by X-
[
12]
ray crystallography in the solid state.
Given the premise of the activation of a,b-unsaturated 7-
I
azaindoline amide 4a with the Cu complex, conditions for
enantioselective addition of angelica lactone 2a to 4a were
screened in combination with Barton’s base as a Brønsted base
(Table 1). Chiral biaryl-type bisphosphines quickly emerged as
[10]
a soft Lewis acid/Brønsted base cooperative catalysis. We an-
ticipated that this activation mode would be valid for electro-
philic activation; the combination of the a,b-unsaturated 7-
azaindoline amide and a soft Lewis acid produces a similar
chelated structure with a Z-amide conformation, exhibiting en-
hanced electrophilicity at the b-carbon to accept the nucleo-
philic addition of in situ generated active nucleophiles. To ex-
plore catalytic asymmetric conjugate addition to the a,b-unsa-
turated 7-azaindoline amides, conformational analysis was con-
ducted with archetypal a,b-unsaturated amide 4a bearing a b-
Ph group (Figure 1). The E-conformation of 4a was unequivo-
cally confirmed in solid state by X-ray crystallography, and the
Table 1. Catalytic asymmetric conjugate addition of angelica lactone 2a
[a]
to a,b-unsaturated 7-azaindoline amide 4a
[b]
[c]
Entry Chiral
ligand
x Brønsted y T
t
Yield
anti/
syn
ee
[%]
[
b]
1
base
[8C] [h] [%]
conformation was retained in solution according to H NMR
analysis in [D ]THF. Although characteristic olefinic protons ap-
1
2
3
4
5
6
7
8
(R)-Binap
5 Barton’s
base
5 Barton’s
base
5 Barton’s
base
5 Barton’s
base
5 Barton’s
base
5 Barton’s
base
5 Barton’s
base
5 Barton’s
base
5
5
5
5
5
5
5
0
0
0
0
0
0
0
3
3
3
3
3
3
3
3
>99
>99
>99
>99
23
4/1 54
8
peared with the b-proton (H ) more downfield than the a-
b
(R)-xyl-Binap
(R)-Segphos
13/1 92
3/1 58
(R)-xyl-Segphos
13/1 85
>20/1 97
9/1 87
(R)-DTBM-Seg-
phos
(R)-xyl-MeO-
Biphep
(R)-DTBM-MeO-
Biphep
(R)-xyl-Binap
>99
12
14/1 96
>20/1 96
17/1 96
5 À40
>99
43
0
0
>99
9
1
(R)-xyl-Binap
(R)-xyl-Binap
(R)-xyl-Binap
(R)-xyl-Binap
5 DBU
5 À40
5 À40
5 À40
5 À40
3
3
3
1
0
5 iPr
5 Et
2
NEt
N
–
–
–
–
1
1
3
[
d]
1
2
1 Barton’s
base
>20/1 96
1
1
3
4
(R)-xyl-Binap
–
1 –
0 Barton’s
base
0 À40 24
5 À40 24
0
0
–
–
–
–
Figure 1. Conformational change of a,b-unsaturated 7-azaindoline amide 4a
was evidenced by H NMR and X-ray crystallographic analysis. Color code for
X-ray structure: hydrogen white, carbon gray, nitrogen blue, oxygen red,
phosphorus orange, copper green.
1
[
[
a] 2a: 0.3 mmol, 4a: 0.1 mmol. [b] Determined by H NMR analysis.
c] Values of ee of anti diastereomer; determined by chiral stationary-
1
phase HPLC analysis. [d] 2a: 0.15 mmol, 4a: 0.1 mmol. Isolated yield.
Chem. Eur. J. 2016, 22, 5525 – 5529
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ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
suitable ligands in this catalytic system to give the desired con-
Table 2. Substrate scope of g-substituted b,g-unsaturated g-butyro-
lactones 2 to a,b-unsaturated 7-azaindoline amides 4.
jugate adduct 5a at 08C with reasonable stereoselectivity
[a]
(
Table 1, entries 1–7). Although we observed higher stereose-
lectivity by increasing the steric factor of the substituents on
phosphorous, ligands with DTBM substituents significantly re-
tarded the reaction (Table 1, entries 5, 7). A less bulky ligand,
for example, (R)-xyl-Binap, at a lower temperature (À408C) ex-
[
13]
clusively gave anti-5a with high enantioselectivity (entry 8).
[
b]
[d]
Entry
1
4
R
2
R
x
pdt
t
Yield
anti
/syn
ee
[%]
Barton’s base was indispensable, and other common amine
bases performed worse under otherwise identical conditions
1
2
[c]
[h] [%]
Ph 4a
Ph 4a
2-MeC
3-MeC
4-MeC
4-CF
4-FC
6 4
4-ClC H
2-BrC
4-BrC
4-AcOC
4-NCC
2-MeOC
3-MeOC
4-MeOC
2-TBSOC
4-TBSOC
Me 2a
Me 2a 0.1 5a
1
5a
1
48
1
1
1
1
1
1
1
1
1
1
3
3
3
2
1
1
1
1
1
1
>99
91
>20/1 96
>20/1 96
>20/1 97
>20/1 96
16/1 97
>20/1 93
>20/1 96
>20/1 95
>20/1 98
>20/1 95
20/1 95
>20/1 91
>20/1 97
>20/1 93
>20/1 97
13/1 91
>20/1 97
>20/1 95
>20/1 96
>20/1 96
>20/1 97
>20/1 92
>20/1 93
>20/1 92
(
Table 1, entries 9–11). Although these reactions were run for
[e]
2
three hours to screen various conditions, the reaction seemed
to proceed rapidly and reached completion within 1 h; the
conditions could be further optimized to as little as 1 mol% of
3
4
5
6
7
8
9
6
6
6
H
H
H
4
4
4
4b
4c
4d
4e
Me 2a
Me 2a
Me 2a
Me 2a
Me 2a
Me 2a
Me 2a
Me 2a
Me 2a
Me 2a
Me 2a
Me 2a
Me 2a
Me 2a
Me 2a
Me 2a
Me 2a
Me 2a
1
1
1
1
1
1
1
1
1
1
3
3
3
3
1
1
1
1
1
1
1
1
5b
5c
5d
5e
5 f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
5r
97
>99
>99
>99
>99
>99
>99
>99
95
98
99
99
>99
91
>99
98
93
>99
88
99
I
[14]
3
C
H
6
H
4
the Cu catalyst and 1.5 equivalents of 2a (entry 12). The co-
6
4
4 f
4g
I
operative work of Cu complex and Barton’s base was crucial
to activate both the electrophile (4a) and nucleophile (2a),
and the reaction did not proceed at all in the absence of
either (Table 1, entries 13, 14). The expeditious progress of the
reaction was specific for 7-azaindoline amide. Other a,b-unsa-
turated carboxylic acid derivatives 6–10 gave no reaction
under these catalytic conditions (Figure 2); indoline amide 6,
isomeric azaindoline amide 7, and dimethylamide 9 were not
6
H
H
4
4
4h
4i
10
6
1
1
6
H
4
4j
4k
1
1
14
2
3
6
H
4
[f]
6
6
6
H
H
H
H
H
4
4
4
4l
[
f]
f]
4m
4n
4o
4p
[
1
1
1
1
5
6
7
8
6
4
6
4
I
able to form a bidentate coordination with Cu and the reac-
3-pyridyl 4q
2-thienyl 4r
(E)-cinnamyl 4s
tions failed. N-Methyl-(2-pyridyl)amide (8) was unreactive de-
spite its bidentate coordination capability. Esters, including
benzylidene malonate 11, were not sufficiently electrophilic.
19
2
2
2
2
2
0
1
2
3
4
5s
5t
5u
5ab 12
5ac 12
3
(E)-CH CH=CH 4t Me 2a
PhCꢀC 4u
Me 2a
Bn 2b
allyl 2c
Ph 4a
98
99
Ph 4a
[
a] 2: 0.15 mmol, 4: 0.1 mmol. [b] Isolated yield. [c] Determined by
H NMR analysis. [d] Value of ee of anti diastereomer; determined by
1
chiral stationary-phase HPLC analysis. [e] Run on 1.25 g of 4a; 6 mol% of
Barton’s base was used. [f] 3 equiv of 2a (0.3 mmol) was used.
Figure 2. Structure of unsuccessful electrophiles.
quired (Table 2, entries 23, 24). Catalyst loading could be re-
duced to as little as 0.1 mol% and run on gram scale (entry 2).
b-Alkyl amide 4v exhibited poor reactivity and diastereoselec-
Substrate scope is delineated in Table 2, showing the
production of conjugate adducts bearing consecutive tri- and
tetrasubstituted stereogenic centers, mostly within one hour
with 1 mol% of catalyst loading. Irrespective of the substitu-
tion pattern of the Me group on the b-aryl substituent, gener-
ally high reactivity and stereoselectivity were observed (en-
tries 3–5). Various electron-withdrawing groups, for example,
tivity, whereas b-CF amide 4w unexpectedly gave the syn-dia-
3
stereomer predominantly with high yield (Scheme 2a). A slight
ÀCF , ÀF, ÀCl, ÀBr, ÀOAc, and ÀCN, on the b-aryl substituent
3
were tolerated (Table 2, entries 6–12). Electron-donating MeO
or TBSO groups retarded the reaction, requiring 3 mol% of cat-
alyst loading for completion, albeit with uniformly high stereo-
selectivity (entries 13–16). Soft Lewis basic heteroaromatics,
I
which may potentially coordinate to Cu catalyst and suppress
the catalysis, had little negative effect (Table 2, entries 18, 19).
1
,4-Addition exclusively proceeded with amide-conjugated 1,3-
dienes 4s and 4t and 1,3-enyne 4u without forming 1,6-ad-
ducts (Table 2, entries 20–22). g-Bn- and g-allyl-substituted b,g-
unsaturated g-butyrolactones 2b and 2c were also applicable
to give the corresponding products 5ab and 5ac in high yield
and stereoselectivity, although a longer reaction time was re-
Scheme 2. Reactions of b-alkyl and b-fluoroalkyl amides.
Chem. Eur. J. 2016, 22, 5525 – 5529
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ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
Scheme 3. Transformation of the products.
modification of the conditions, (R)-DTBM-Segphos as the
ic tert-butyldimethylsilyl (TBS) ether with identical conditions
gave bicyclic compound 15 via hydrolysis/desilylation and sub-
sequent phenol-selective cyclization.
ligand and iPr O as the solvent, enhanced the syn-preference,
2
as well as enantioselectivity, which was also valid for b-C F
2
5
[15]
amide 4x (Scheme 2b).
were barely detected, suggesting that b-fluoroalkyl substrates
w and 4x kinetically favored the formation of the syn-
Retro-reaction and epimerization
In conclusion, a,b-unsaturated 7-azaindoline amides, which
are in the carboxylic acid oxidation state, served as reactive
conjugate addition acceptors when using butyrolactones as
nucleophiles in a cooperative catalytic system. Reactions
mostly completed with 1 mol% of the catalyst with high
stereoselectivity, and the observed anti-selectivity was com-
plementary to the prior art by using imides and unsaturated
thioamides as electrophiles. The amide moiety was chemo-
selectively hydrolyzed for further manipulations.
4
diastereomer.
a,b-Unsaturated g-butyrolactones 12 were also applicable in
the present catalytic system to give 13 bearing consecutive
trisubstituted stereogenic centers (Table 3). The reaction was
Table 3. Substrate scope of b-substituted a,b-unsaturated g-butyro-
[
a]
lactones 12 to a,b-unsaturated 7-azaindoline amides 4.
Acknowledgements
This work was financially supported by JST, ACT-C, and KAKEN-
HI (No. 25713002) from JSPS. Dr. Tomoyuki Kimura is gratefully
acknowledged for X-ray crystallographic analysis of 4a,
I
[
b]
[d]
4a/Cu /rac-xyl-Binap complex, anti-5a, syn-5w, rac-syn-5x, and
Entry
1
4
R
12
R
x
pdt
t
Yield
anti/
syn
ee
[%]
1
2
[c]
[h] [%]
anti-13ab. Dr. Ryuichi Sawa, Ms. Yumiko Kubota, and Dr.
Kiyoko Iijima are gratefully acknowledged for the NOE analysis
of the Cu/amide complex.
Ph 4a
2-MeC
3-MeC
4-MeC
4-CF
4-FC
4-ClC H
6 4
2-BrC
4-BrC
H 12a
H 12a
H 12a
H 12a
H 12a
H 12a
H 12a
H 12a
H 12a
1
1
1
1
1
1
1
1
1
3
1
1
13a
13b
13c
13d
13e
13 f
13g
13h
13i
3
3
98
94
>20/1 95
>20/1 93
>20/1 97
>20/1 96
>20/1 92
>20/1 96
>20/1 97
>20/1 90
>20/1 95
>20/1 98
>20/1 98
>20/1 97
[e]
2
3
4
5
6
7
8
9
1
6
6
6
H
H
H
4
4
4
4b
4c
4d
4e
24 95
24 95
24 92
24 97
24 99
24 99
24 92
24 95
24 91
Keywords: asymmetric catalysis · azaindoline · butenolide ·
conjugate addition · cooperative catalysis
3
6 4
C H
6
H
4
4 f
4g
[
e]
6
H
H
4
4
4h
4i
[
1] For reviews, see: a) D. Almasi, D. A. Alonso, C. Nµjera, Tetrahedron:
Asymmetry 2007, 18, 299; b) J. Christoffers, G. Koripelly, A. Rosiak, M.
Rçssle, Synthesis 2007, 1279; c) S. B. Tsogoeva, Eur. J. Org. Chem. 2007,
6
0
4-MeOC
2-thienyl 4r
Ph 4a
6
H
4
4n H 12a
H 12a
13n
13r
13ab
1
1
1
2
1
701; d) J. L. Vicario, D. Badía, L. Carrillo, Synthesis 2007, 2065; e) S.
[e]
Me 12b
3
93
Sulzer-MossØ, A. Alexakis, Chem. Commun. 2007, 3123; f) A. Alexakis, J.-
E. Bäckvall, N. Krause, O. Pµmies, M. DiØguez, Chem. Rev. 2008, 108,
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[
1
a] 12: 0.3 mmol, 4: 0.1 mmol. [b] Isolated yield. [c] Determined by
H NMR analysis. [d] Value of ee of anti diastereomer; determined by
chiral stationary-phase HPLC analysis. [e] (R)-xyl-Binap was used as
a chiral ligand.
[
2] For reviews of natural products containing butenolides, see: a) A. Ber-
mejo, B. FigadØre, M. Zafra-Polo, I. Barrachina, E. Estornell, D. Cortes,
Nat. Prod. Rep. 2005, 22, 269; b) J. D. Sellars, P. G. Steel, Eur. J. Org.
Chem. 2007, 3815; c) I. Prassas, E. P. Diamandis, Nat. Rev. Drug Discovery
I
promoted by only 1 mol% of Cu catalyst and more sterically
demanding (R)-DTBM-Segphos was optimal for less bulkier nu-
cleophile 12a, except for the reactions of unsaturated amide
2
008, 7, 926; d) P. A. Roethle, D. Trauner, Nat. Prod. Rep. 2008, 25, 298.
[3] For the concept of vinylogy, see: a) R. C. Fuson, Chem. Rev. 1935, 16, 1;
b) S. Krishnamurthy, J. Chem. Educ. 1982, 59, 543.
4] a) G. Casiraghi, F. Zanardi, L. Battistini, G. Rassu, Synlett 2009, 1525; b) G.
4
b and i bearing an o-Me or o-Br group, with which less bulky
[
(
R)-xyl-Binap performed better (Table 3, entries 2, 8). Amide 4n
Casiraghi, L. Battistini, C. Curti, G. Rassu, F. Zanardi, Chem. Rev. 2011,
with an electron-donating p-MeO group required 3 mol% of
the catalyst (entry 10), and b-Me substituted nucleophile 12b
also preferred (R)-xyl-Binap (Table 3, entry 12) as a chiral ligand.
The 7-azaindoline moiety of product 5a could be readily hy-
drolyzed to give 14 under acidic conditions with the butyrolac-
tone ring intact (Scheme 3). Treatment of 5o bearing a phenol-
1
11, 3076.
[5] For a review, see: Q. Zhang, X. Liu, X. Feng, Curr. Org. Synth. 2013, 10,
64.
6] For recent examples of catalytic asymmetric conjugate addition using
-siloxyfurans as pre-activated butenolides, see: a) S. P. Brown, N. C.
7
[
2
Goodwin, D. W. C. MacMillan, J. Am. Chem. Soc. 2003, 125, 1192; b) Y.
Huang, A. M. Walji, C. H. Larsen, D. W. C. MacMillan, J. Am. Chem. Soc.
Chem. Eur. J. 2016, 22, 5525 – 5529
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ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
2
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[11] Confirmed by H– C HMBC analysis; see the Supporting Information.
[12] Single crystal was obtained from the [Cu(CH
mixture.
3 4 6
CN) ]PF /rac-xyl-Binap/4a
Wu, X.-Q. Huang, D.-F. Yue, Y. You, X.-Y. Xu, X.-M. Zhang, W. C. Yuan,
Chem. Commun. 2015, 51, 15835.
[13] Absolute configuration was determined by X-ray crystallographic analy-
sis; see the Supporting Information for details.
[14] Reducing the amount of Barton’s base to 1 mol% led to a significant
decrease in the yield.
[
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2
[15] Products 5v and w were highly insoluble in iPr O, and the clear reac-
tion mixture became a white suspension, even at 0.03m, when the re-
action proceeded.
1
26, 5431.
[
9] For the utility of 7-azaindoline amide for direct enolization, see: a) K.
Received: February 17, 2016
Weidner, N. Kumagai, M. Shibasaki, Angew. Chem. Int. Ed. 2014, 53,
Published online on March 10, 2016
Chem. Eur. J. 2016, 22, 5525 – 5529
www.chemeurj.org
5529
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