Boron Tribromide-Assisted Chiral Phosphoric Acid Catalyst for a Highly Enantioselective Diels-Alder Reaction of 1,2-Dihydropyridines

Article abstract of DOI:10.1021/jacs.5b08693

BBr₃-chiral phosphoric acid complexes are highly effective and practical Lewis acid-assisted Bronsted acid (LBA) catalysts for promoting the enantioselective Diels-Alder (DA) reaction of α-substituted acroleins and α-CF₃ acrylate. In particular, the DA reaction of α-substituted acroleins with 1,2-dihydropyridines gave the corresponding optically active isoquinuclidines with high enantioselectivities. Moreover, transformations to the key intermediates of indole alkaloids, catharanthine and allocatharanthine, are demonstrated.

Full text of DOI:10.1021/jacs.5b08693

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Communication
Boron Tribromide-Assisted Chiral Phosphoric Acid Catalyst for a
Highly Enantioselective Diels-Alder Reaction of 1,2-Dihydropyridines
Manabu Hatano, Yuta Goto, Atsuto Izumiseki, Matsujiro Akakura, and Kazuaki Ishihara
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b08693 • Publication Date (Web): 12 Oct 2015
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Boron Tribromide-Assisted Chiral Phosphoric Acid Catalyst
for a Highly Enantioselective Diels–Alder Reaction of 1,2-
Dihydropyridines
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Manabu Hatano,† Yuta Goto,† Atsuto Izumiseki,† Matsujiro Akakura,‡ Kazuaki Ishihara*,†
†Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8603, Japan
‡Department of Chemistry, Aichi University of Education, Igaya-cho, Kariya 448-8542, Japan
Supporting Information Placeholder
ABSTRACT: BBr3–chiral phosphoric acid complexes
were highly effective and practical Lewis acid-assisted
Brønsted acid (LBA) catalysts for promoting the enanti-
oselective Diels–Alder (DA) reaction of α-substituted
acroleins and α-CF3 acrylate. In particular, the DA reac-
tion of α-substituted acroleins with 1,2-dihydropyridines
gave the corresponding optically active isoquinuclidines
assisted chiral phosphoric acid in situ, which was highly
effective for the enantioselective Diels–Alder reaction of
α-substituted acroleins with 1,2-dihydropyridines to
afford the synthetically useful optically active isoquinu-
clidine scaffold.
We initially examined the reaction of methacrolein 3a
with cyclopentadiene 2a through the use of chiral phos-
phoric acid (R)-1a (5 mol%) and an achiral Lewis acid
(2.5–10 mol%) in dichloromethane at –78 °C for 3 h
(Table 1). The reaction was slow with the use of (R)-1a
alone at –78 °C or room temperature to afford 4a with
poor enantioselectivity (entries 1 and 2). Through pre-
liminary investigations, we found that boron compounds
were highly effective as achiral Lewis acids for (R)-1a
with high enantioselectivities.
Moreover, transfor-
mations to the key intermediates of indole alkaloids,
catharanthine and allocatharanthine, are demonstrated.
Chiral phosphoric acids are highly useful acid–base co-
operative organocatalysts for a variety of asymmetric
catalyses.1 However, their Brønsted acidity is generally
not strong enough to activate less-basic aldehydes rather
than more-basic aldimines. To overcome this serious
issue, stronger Brønsted acid catalysts, such as chiral
BINOL (1,1’-bi-2-naphthol)-derived N-sulfonyl phos-
phoramides,2a N-phosphinyl phosphoramides,2b and di-
sulfonimides2c have been developed. In sharp contrast,
we envisioned that the addition of an achiral Lewis acid
to the chiral phosphoric acid would be highly promising
since the conjugate acid–base moiety of the phosphoric
acid is suitable for the Lewis acid-assisted Brønsted acid
(LBA)3 catalyst system (Scheme 1). As a great advanta-
ge of this LBA system, we can simply use highly practi-
cal chiral phosphoric acids without serious synthetic
difficulties. In particular, we developed here a BBr3-
Table 1. Optimization of the Reaction Conditionsa
4-Ph-C6H4
O
O
O
P
OH
4-Ph-C6H4
(R)-1a (5 mol%)
CHO
+
+
Lewis acid (2.5–10 mol%)
CHO
CHO
CH2Cl2, –78 ºC, 3 h
exo-4a
2a
3a
endo-4a
entry Lewis acid (mol%)
yield (%)
endo:exo
ee (%) of exo-4a
1
2b
3
–
–
0
–
–
–7
5
51
64
87
88
92
99
78
64
98
66
13:87
10:90
3:97
4:96
3:97
2:98
2:98
8:92
7:93
10:90
B(C6F5)3 (5)
BF3·Et2O (5)
BCl3 (5)
BBr3 (2.5)
BBr3 (5)
BBr3 (7.5)
BBr3 (10)
BI3 (5)
4c
5
52
62
61
89
85
18
37
–
6
7
8
9
Scheme 1. Achiral Lewis acid-assisted chiral phosphoric
acid catalysts as chiral acid–base cooperative catalysts.
10
11d
BBr3 (5)
–
Xδ
M
Lewis base
Lewis acid
O
Ar
O
Ar
O
–
–
Xδ
a The reaction was carried out with (R)-1a (5 mol%), Lewis acid (2.5–
10 mol%), 2a (5 equiv), and 3a (1 equiv) in dichloromethane at –
Xδ
O
+
MX3
P
P
b
+
!
78 °C for 3 h. The reaction was conducted at room temperature for
O
O
H
O
O
H3δ
c
d
3 h. Et2O was removed in vacuo during catalyst preparation. The
reaction was conducted without (R)-1a.
Activated
Brønsted acid
Ar
Ar
Brønsted acid
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Journal of the American Chemical Society
(entries 3–10). In particular, BBr3 (entry 7) showed
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2,6-(i-Pr)2-4-Ph-C6H4
higher enantioselectivity than other similar compounds,
such as B(C6F5)3, BF3·Et2O, BCl3, and BI3. The amount
of BBr3 was important, and the use of more or less than
5 mol% of BBr3 for 5 mol% of (R)-1a decreased the
yield and/or enantioselectivity (entries 6–9). The reac-
tion proceeded moderately with the use of 5 mol% of
BBr3 in the absence of (R)-1a (entry 11). Therefore, this
result strongly suggests that the LBA catalyst BBr3–(R)-
1a in situ might show higher catalytic activity than ei-
ther starting component, (R)-1a and BBr3.
O
O
O
P
NHTf
Br
CHO
2,6-(i-Pr)2-4-Ph-C6H4
(R)-1b (10 mol%)
H
BBr3 (5 mol%)
+
(1)
3b
MeO
CH2Cl2
MeO
endo-6
5
–78 ºC, 5 h
9
82% (endo:exo = >99:1)
89% ee (endo)
10
11
12
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cf.
(R)-1a/BBr3 (10/10 mol%): 35% (endo:exo = >99:1)
16% ee (endo)
With the optimized reaction conditions in hand, we
next examined the scope of α-substituted acroleins 3a–c
with 2a and cyclohexadiene 2b (Scheme 2). As a result,
exo-adduct 4b was obtained with 86% ee as a major
product with the use of 2a, while endo-adducts 4c–e
were obtained with 87–94% ee as major products with
the use of 2b, according to the usual substrate-dependent
endo/exo-controls.4 Interestingly, the reactivity of the
substrates strongly influences the optimized molar ratio
of BBr3 to (R)-1a, and a slightly excess amount of BBr3
to (R)-1a was effective for more reactive α-
haloacroleins 3b and 3c in place of less reactive 3a to
achieve high enantioselectivities for 4b, 4d, and 4e.5
(R)-1b (10 mol%)
CF3
BBr3 (5 mol%)
+
CO2Me
CF3
exo-8
+
2a
(2)
CO2Me
F3C
CO2Me
MS 5Å, CH2Cl2
–78 ºC, 5 h
7
endo-8
>99% (endo:exo = 86:14)
93% ee (endo)
cf.
(R)-1a/BBr3 (10/15 mol%): 86% (endo:exo = 91:9)
77% ee (endo)
We next performed the reaction with 1,2-
dihydropyridine 9a, which can provide synthetically
useful optically active isoquinuclidines.8 The reactions
of 9a and acrolein 3e proceeded smoothly with the use
of BBr3–(R)-1a catalyst, and the key compound 10d for
the important anti-influenza drug oseltamivir phosphate
(tamiflu®)9 was obtained in 96% yield with 94% ee
(Scheme 3). Rawal previously reported the Lewis acidic
chiral salen Cr(III)-catalyzed reaction of 9a with 3a, as a
sole example using α-substituted acrolein, and 10a was
obtained with 67% ee.8a Moreover, the MacMillan cata-
lyst 11, which was reported to be an excellent chiral
secondary amine catalyst for the reaction of 3e by Fuku-
yama,10 could not be used for the reaction of 3a, proba-
bly due to the steric constraints in the iminium interme-
diate 12 (eq 3). Fortunately, in our Brønsted acid cataly-
sis, not only 3e but also α-substituted acroleins 3a, 3b,
and 3d could be used successfully, and the corre-
sponding products 10a, 10b, and 10c were obtained with
92–98% ee, respectively (Scheme 3). Moreover, the
Scheme 2. Reactions of α-Substituted Acroleins.
n
n
(R)-1a (10 mol%)
CHO
+
BBr3 (10–15 mol%)
+
n
R
CHO
R
R
CH2Cl2
2a (n = 1)
3a (R = Me)
CHO
endo-4
2b (n = 2) 3b (R = Br)
3c (R = Cl)
–78 ºC, 3–5 h
exo-4
Products 4, reaction time, yield, and enantioselectivity.
CHO
Me
CHO
Br
Cl
Br
CHO
CHO
endo-4e
5 h, 88% yielda
endo-4d
3 h, >99% yielda
exo-4b
3 h, >99% yielda
endo-4c
4 h, 88% yieldb
endo:exo = 5:95 endo:exo = 97:3
86% ee (exo) 87% ee (endo)
endo:exo = 94:6 endo:exo = 94:6
91% ee (endo) 94% ee (endo)
a 15 mol% of BBr3 was used. b 10 mol% of BBr3 was used.
Scheme 3. Reactions of 1,2-Dihydropyridines.
In place of 2, less reactive acyclic diene 5 was exam-
ined (eq 1). Although BBr3–(R)-1a showed low catalyt-
ic activity (16% ee) even under the optimized conditions
in this case, BBr3–N-sulfonyl phosphoramide (R)-1b
was much more effective than BBr3–(R)-1a, and endo-6
was obtained with 89% ee. Moreover, 7 with an elec-
tron-withdrawing CF3 group was examined in place of
acroleins (eq 2). BBr3–(R)-1b gave better results than
BBr3–(R)-1a,6 and the corresponding endo-8 was ob-
tained as a major product with 93% ee. Although only
the specialized acrylate 7 was shown at this stage, the
enantioselective Diels–Alder reactions of α-substituted
acrylates with chiral Brønsted acid catalysts might be
valuable since α-substituted acrylates have not yet been
used with any conventional chiral Lewis acid catalysts.4,7
PhO2C
CO2Ph
(R)-1a (10 mol%)
PhO2C
N
N
BBr3 (10–15 mol%)
N
+
CHO
R
CHO
+
R
CH2Cl2, MS 5Å
–78 ºC, 3–5 h
3a (R = Me)
3b (R = Br)
3d (R = Et)
3e (R = H)
R
CHO
endo-10
9a
exo-10
Products 10, reaction time, yield, and enantioselectivity.
PhO2C
PhO2C
PhO2C
PhO2C
N
N
N
N
Br
Me
CHO
endo-10a
Et
H
CHO
endo-10b
5 h, 63% yieldb
endo:exo = >99:1
98% ee (endo)
CHO
endo-10c
5 h, 58% yielda
CHO
endo-10d
3 h, 96% yielda
3 h, 82% yielda
endo:exo = >99:1
95% ee (endo)
endo:exo = >99:1 endo:exo = 99:1
92% ee (endo) 94% ee (endo)
a 10 mol% of BBr3 was used. b 15 mol% of BBr3 was used.
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Scheme 5. Formal Total Synthesis of (+)-Allocatharanthine.
O
O
N
N
1
2
3
(S)-1a (10 mol%)
BBr3 (15 mol%)
ArO2C
Bn
HCl·H
CO2Ar
N
Et
Bn
Me
N
N
N
+
3b
Br
11 (10 mol%)
H
CH2Cl2, MS 5Å
–78 ºC, 5 h
(3)
+
10a
9a
3a
4
CHO
CH3CN, H2O
rt, 24 h
Et
0%
12
endo-10e, 97% ee
69% (endo:exo = 96:4)
9b (Ar = 4-Cl-C6H4)
5
6
7
PhO2C
Br
1) NaClO2, NaH2PO4·2H2O
2-methyl-2-butene
t-BuOH-H2O, rt, 2 h
1) NaClO2, NaH2PO4
2-Methyl-2-butene
t-BuOH/H2O, rt, 2 h
O
ArO2C
MeO2C
Et
Et
N
N
N
Br
O
NaOMe, MeOH
60 °C, 24 h
N
Br
O
(4)
Br
Br
8
10b
2) MeI, K2CO3
DMF, rt, 3 h
O
2) Br2, NaHCO3 aq.
CH2Cl2, rt, 30 min
O
CO2Me
CO2Me
9
O
17, 83% (2 steps)
18, 63%
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
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60
13, 87%
Br
O
1) Me3SiI
CH2Cl2, rt, 12 h
Et
Et
novel compound 10b was readily transformed to the γ-
lactone 13 in 87% yield, and its stereochemistry was
determined by X-ray analysis (eq 4).
N
N
ref. 14
Br
N
2) 3-Indoleacetic acid
t-BuCOCl, Et3N
DMF, rt, 24 h
N
H
H
CO2Me
CO2Me
19, 83% (2 steps)
(+)-allocatharanthine
To demonstrate the synthetic utility of our catalytic
system, we performed a formal total synthesis of (+)-
catharanthine, which is an important indole alkaloid that
forms vinblastine, which has high antitumor activities
(Scheme 4).11 After Diels–Alder product 10b was re-
duced to the alcohol with NaBH4, epoxidation under
basic conditions gave 14. Treatment of 14 with aqueous
ammonia and subsequent oxidation with sodium perio-
date gave the ketone 15. Acetalization of 15 with
(Me3SiOCH2)2/Me3SiOTf and subsequent transesterifi-
cation provided the desired key compound 1612 without
a loss of optical purity. These easy high-yield transfor-
mations in six steps from 10b to 16 might be attractive
as a concise synthesis of (+)-catharanthine.
BBr3–(R)-1a, was observed as a major peak at –6.0 ppm
at –78 °C, which was shifted from the original peak of
(R)-1a at 2.4 ppm (eq 5, also see the SI with 11B NMR).
In contrast, the catalyst obtained by preparation at room
temperature gave many new peaks at +5 to –25 ppm,
which might be attributed to boronphosphonate deriva-
tives 20 after the release of HBr (eq 6, also see the SI
with 11B NMR). Actually, the release of HBr at room
temperature was confirmed by the generation of 22 from
1-methyl-1-cyclohexene 2116 as a HBr-scavenger (eq 7,
also see the SI). Moreover, the reaction between 2a and
3a with the use of 20 and 21 provided 4a with low enan-
tioselectivity (eq 6). In contrast, upon the addition of 21
to BBr3–(R)-1a, which was prepared at –78 °C in ad-
vance, the enantioselectivity was essentially the same
(eq 5 v.s. Table 1, entry 7). This result suggests that ad-
ventitious HBr, which would induce an uncatalyzed re-
action, might not be generated in situ at –78 °C. By the
LBA-strategy for phosphoric acids, which is different
from the design of metal phosphates as bifunctional
Lewis acid catalysts,1c,17 powerful Brønsted acid cata-
Scheme 4. Formal Total Synthesis of (+)-Catharanthine.
1) NH3 aq.
rt, 9 h
PhO2C
PhO2C
1) NaBH4
THF-H2O, rt, 1 h
N
N
endo-10b
2) NaIO4, NaH2PO4
H2O, rt, 15 h
2) NaOH aq.
dioxane, rt, 3 h
92% ee
O
O
15, 77% (2 steps)
14, 91% (2 steps)
MeO2C
N
1) (Me3SiOCH2)2
Me3SiOTf
CH2Cl2, –20 °C, 12 h
N
1
ref. 12
O
O
lysts can be easily obtained in situ (See the SI for H
NMR for PO2H).
N
H
Et
2) NaOMe, MeOH
reflux, 16 h
CO2Me
(+)-catharanthine
16, 97% (2 steps)
92% ee
31P NMR analysis and catalysis:
2a, 3a
BBr3
(R)-1a (5 mol%)
+2.4 ppm
Moreover, we performed a transformation to the key
intermediate of (+)-allocatharanthine, which is another
component of vinblastine (Scheme 5).13 Actually, the
enantioselective Diels–Alder reactions of alkyl-
substituted 1,2-dihydropyridines are still limited with the
use of 3e.8f As a great advantage of our catalytic system,
the Diels–Alder reaction of 9b with 3b gave the desired
10e as a major product with the use of BBr3–(S)-1a.
Aldehyde 10e was transformed to ester 17 and subse-
quent transesterification provided ester 18. After N-
decarbomethoxylation of 18, condensation with 3-
indoleacetic acid gave the desired key intermediate 1914.
21 (50 mol%)
O
O
O
(5)
(6)
P
CH2Cl2
–78 ºC, 1 h
–78 ºC, 3 h
BBr3 (5 mol%)
OH
endo-4a + exo-4a
BBr3–1a
>99% (endo:exo = 2:98)
88% ee (exo, 2S)
–6.0 ppm (major)
2a, 3a
O
O
O
O
BBry
BBrz
21 (50 mol%)
(R)-1a (5 mol%)
BBr3 (5 mol%)
P
CH2Cl2
rt, 1 h
then –78 ºC
–78 ºC, 3 h
x
endo-4a + exo-4a
20
80% (endo:exo = 10:90)
16% ee (exo, 2R)
+5 ~ –25 ppm
(many peaks)
1H NMR analysis:
Br
(7)
+
+
(R)-1a
BBr3
CD2Cl2, 1 h
H
(1 equiv) (1 equiv)
22
21 (1 equiv)
–78 ºC: Not detected
rt: >99%
Finally, we turn our attention to mechanistic aspects.
To identify a possible P=O···BBr3 structure without the
generation of HBr15, we performed a 31P NMR analysis
of a 1:1 molar ratio of (R)-1a and BBr3 in dichloro-
methane (eq 5). As a result, a new signal, indicating
A possible structure of the BBr3–1a–3b complex was
considered based on theoretical calculations (See the SI
in detail). In the optimized geometry, the P=O moiety of
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Journal of the American Chemical Society
Page 4 of 5
(3) For a review: (a) Ishibashi, H.; Ishihara, K.; Yamamoto, H.
Chem. Rec. 2002, 2, 177. (b) Yamamoto, H.; Futatsugi, K. Angew.
Chem. Int. Ed. 2005, 44, 1924.
(R)-1a coordinates to BBr3 and the C=O moiety of 3b
coordinates to the proton of phosphoric acid (see the SI).
Moreover, two hydrogen bonds for 3b, such as Br···H–
C=O and Br···H–C=C, were observed. These hydrogen
bonding interactions show that the base function of the
LBA shifts from the original P=O moiety to the terminal
Br moiety, and thus the BBr3–(R)-1a complex would
also act as an acid–base cooperative catalyst.
1
2
3
4
5
6
7
8
(4) (a) Kagan, H. B.; Riant, O. Chem. Rev. 1992, 92, 1007. (b) Du,
H.; Ding, K. in Handbook of Cyclization Reactions, ed. Ma, S. Wiley-
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Weinheim, 2011, vol. 3, pp. 67–123.
(5) Excess BBr3 might act as the dimer (BBr3)2, which has stronger
Lewis acidity than BBr3. Also see the SI in detail. Schmulbach, C.
D.; Ahmed, I. Y. J. Mol. Struct. 1994, 320, 57.
9
(6) BBr3–(R)-1b did not always give better results than BBr3–(R)-
1a. For example, BBr3–(R)-1b was not suitable for reactive acroleins
and cyclic dienes, as shown in Table 1 and Schemes 2 and 3.
(7) Yamamoto reported a preference of Brønsted acid catalysts
over bulky Lewis acids in the coordination to sterically hindered ke-
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catalysts for esters might be possible. Nakashima, D.; Yamamoto, H.
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Swaminathan, S.; Bischofberger, N.; Chen, M. S.; Mendel, D. B.; Tai,
C. Y.; Laver, W. G.; Stevens, R. C. J. Am. Chem. Soc. 1997, 119, 681.
(10) Satoh, N.; Akiba, T.; Yokoshima, S.; Fukuyama, T. Angew.
Chem. Int. Ed. 2007, 46, 5734.
(11) Total synthesis of indole alkaloids via Diels–Alder reactions
of 1,2-dihydropyridines. (a) Büchi, G.; Coffen, D. L.; Kocsis, K.;
Sonnet, P. E.; Ziegler, F. E. J. Am. Chem. Soc. 1965, 87, 2073. (b)
Büchi, G.; Coffen, D. L.; Kocsis, K.; Sonnet, P. E.; Ziegler, F. E. J.
Am. Chem. Soc. 1966, 88, 3099. (c) Ikezaki, M.; Wakamatsu, T.; Ban,
Y. J. Chem. Soc., Chem. Commun. 1969, 88. (d) Büchi, G.; Kulsa, P.;
Ogasawara, K.; Rosati, R. L. J. Am. Chem. Soc. 1970, 92, 999. (e)
Marazano, C.; Le Goff, M.-T.; Fourrey, J.-L.; Das, B. C. J. Chem.
Soc., Chem. Commun. 1981, 389. (f) Raucher, S.; Bray, B. L. J. Org.
Chem. 1985, 50, 3236. (g) Kuehne, M. E.; Bornmann, W. G.; Earley,
W. G.; Marko, I. J. Org. Chem. 1986, 51, 2913. (h) Raucher, S.; Bray,
B. L.; Lawrence, R. F. J. Am. Chem. Soc. 1987, 109, 442. (i) Born-
mann, W. G.; Kuehne, M. E. J. Org. Chem. 1992, 57, 1752. (j) Red-
ing, M. T.; Fukuyama, T. Org. Lett. 1999, 1, 973. (k) Mizoguchi, H.;
Oikawa, H.; Oguri, H. Nature Chem. 2014, 6, 57.
Figure 1. B3LYP/6-31G*-Optimized Geometry of BBr3–
(R)-1a–3b Complex
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n
re face
(favored)
Br
B
2.92 Å
2.72 Å
H
P
H
H
si face
(disfavored)
In summary, we have developed BBr3-assisted chiral
phosphoric acids as highly effective LBA catalysts. In
particular, the enantioselective Diels–Alder reactions of
α-substituted acroleins with 1,2-dihydropyridines pro-
ceeded, and synthetically useful optically active inter-
mediates for bioactive indole alkaloids were obtained.
ASSOCIATED CONTENT
Experimental procedures and characterization data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: ishihara@cc.nagoya-u.ac.jp
Funding Sources
The authors declare no competing financial interest.
(12) Moisan, L.; Thuéry, P.; Nicolas, M.; Doris, E.; Rousseau, B.
Angew. Chem. Int. Ed. 2006, 45, 5334.
ACKNOWLEDGMENT
(13) (a) Brown, R. T.; Hill, J. S.; Smith, G. F.; Stapleford, K. S. .; Pois-
son, J.; Muquet, M.; Kunesch, N. J. Chem. Soc., Chem. Commun. 1969,
1475. (b) Scott, A. I.; Wei, C. C. J. Am. Chem. Soc. 1972, 72, 8266. (c)
Scott, A. I.; Cherry, P. C.; Wei, C. C. Tetrahedron 1974, 30, 3013.
(14) Szántay, C.; Bölcskei, H.; Gács-Baitz, E. Tetrahedron 1990,
46, 1711.
(15) Mukaiyama reported prolinol–BBr3-catalysed Diels–Alder re-
action, in which the active catalyst prepared in situ at room tempera-
ture was believed to be the exchanged-HBr salt of amino boron deriv-
atives. Later, Aggawal showed structural evidence by NMR study.
(a) Kobayashi, S.; Murakami, M.; Harada, T.; Mukaiyama, T. Chem.
Lett. 1991, 20, 1341. (b) Aggarwal, V. K.; Anderson, E.; Giles, R.;
Zaparucha, A. Tetrahedron: Asymmetry 1995, 6, 1301.
Financial support was partially provided by JSPS KA-
KENHI Grant Numbers 15H05755, 26288046, and
26105723, and Program for Leading Graduate Schools
“IGER program in Green Natural Sciences”, MEXT, Japan.
REFERENCES
(1) For reviews: (a) Akiyama, T. Chem. Rev. 2007, 107, 5744. (b)
Terada, M. Synthesis 2010, 1929. (c) Parmar, D.; Sugiono, E.; Raja,
S.; Rueping, M. Chem. Rev. 2014, 114, 9047.
(2) (a) Nakashima, D.; Yamamoto, H. J. Am. Chem. Soc. 2006, 128,
9626. (b) Čorić, I.; List, B. Nature 2012, 483, 315. (c) van Gemmeren,
M.; Lay, F.; List, B. Aldrichimica Acta 2014, 47, 3. (d) Schenker, S.;
Zamfir, A.; Freund, M.; Tsogoeva, S. B. Eur. J. Org. Chem. 2011,
2209. (e) Rueping, M.; Kuenkel, A.; Atodiresei, I. Chem. Soc. Rev.
2011, 40, 4539. (f) Rueping, M.; Nachtsheim, B. J.; Ieawsuwan, W.;
Atodiresei, I. Angew. Chem. Int. Ed. 2011, 50, 6706.
(16) Tanner, D. D.; Zhang, L.; Hu, L. Q.; Kandanarachchi, P. J.
Org. Chem. 1996, 61, 6818.
(17) (a) Rueping, M.; Koenigs, R. M.; Atodiresei, I. Chem. Eur. J.
2010, 16, 9350. (b) Phipps, R. J.; Hamilton, G. L.; Toste, F. D. Nature
Chem. 2012, 4, 603. (c) Lv, J.; Luo, S. Chem. Commun. 2013, 49, 847.
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–
Brδ
–
Brδ
Ar
O
B
–
Brδ
O
Activated
Brønsted acid
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P
O
H3 +
δ
!
O
R1
PhO2C
CO2Ph
N
N
Ar
(10 mol%)
R2
CHO
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R2 CHO
+
R1
CH2Cl2, MS 5A
–78 °C, 3–5 h
58~96% yield
endo:exo = >99:1
up to 98% ee (endo)
R2 = H, Me, Et, Br
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