Reaction rate acceleration enabled by tethered Lewis acid-Lewis base bifunctional catalysis: A catalytic, enantioselective [2+2] ketene aldehyde cycloaddition reaction

Article abstract of DOI:10.1055/s-0029-1217332

A tethered Lewis acid-Lewis base (LA*-LB*) bifunctional catalyst promotes the asymmetric [2+2] cycloaddition reaction between ketene and aldehydes rapidly. The LA*-LB* bifunctional catalyst, a quinine tethered Co(III)-salen complex (5 mol%) catalyzes the

Full text of DOI:10.1055/s-0029-1217332

CLUSTER
1675
Reaction Rate Acceleration Enabled by Tethered Lewis Acid–Lewis Base
Bifunctional Catalysis: A Catalytic, Enantioselective [2+2] Ketene Aldehyde
Cycloaddition Reaction
R
eactionRate
r
A
cceler
i
d
A
symmetr
h
ic Bifunction
a
al Catalysi
r(ABC) Chidara, Yun-Ming Lin*
Department of Chemistry, University of Toledo, 2801 W. Bancroft Street, Toledo, OH 43606, USA
Fax +1(419)5304033; E-mail: Yun-Ming.Lin@Utoledo.edu
Received 2 March 2009
This paper is dedicated to Professor Marvin J. Miller of the University of Notre Dame on the occasion of his 60th birthday.
In addition to Romo’s early strategy for synthesizing bi-
Abstract: A tethered Lewis acid–Lewis base (LA*–LB*) bifunc-
cyclic b-lactones from aldehyde acids,4 Nelson and Calter
tional catalyst promotes the asymmetric [2+2] cycloaddition reac-
independently developed new catalytic methods to syn-
tion between ketene and aldehydes rapidly. The LA*–LB*
bifunctional catalyst, a quinine tethered Co(III)–salen complex (5
thesize chiral b-lactones from aldehydes and substituted
mol%) catalyzes the [2+2] cycloaddition reaction to produce the ketenes.5 Chiral Lewis bases (LB*) and chiral Lewis acids
(LA*) were developed by Fu6a and Corey,6b respectively,
C4-substituted b-lactones in uniformly >99% ee and high isolated
yields (71–97%). The dramatic rate acceleration, the hallmark of
to synthesize b-lactones from pure ketenes. Most recently,
cooperative intramolecular bifunctional catalysis, is achieved for
new catalytic systems developed for the [2+2] cycloaddi-
the catalytic, enantioselective [2+2] cycloaddition reaction between
tion reaction between aldehydes and substituted ketenes
aldehydes and unsubstituted ketene.
were reported by Peters6c,d and Ye,6e respectively. Howev-
Key words: Lewis acids, Lewis bases, bifunctional catalysts, rate
er, no catalytic methods that rapidly produce enantiomer-
acceleration, enantioselectivity
ically pure (i.e. >99% ee) C4-alkyl or aryl b-lactones are
currently available for the [2+2] cycloaddition reaction
between aldehydes and unsubstituted ketene.
Enantiomerically pure b-lactones are valuable small mol-
Employing the [2+2] cycloaddition reaction as a test reac-
ecules that can be converted into a variety of chiral syn-
thons for asymmetric synthesis.1 Because the [2+2]
cycloaddition reaction between ketene and aldehydes af-
fords b-lactones in one step, developing new catalytic
methods for synthesizing b-lactones from ketene and al-
dehydes attracts much attention.1,2 In 1982, Wynberg re-
ported an enantioselective synthesis of b-lactone 5 from
ketene 1 and chloral 3, catalyzed by quinidine (Q*,
Scheme 1).3 This formal [2+2] reaction entails a tandem
aldol–lactonization process (from 2 to 4 to 5) to produce
the b-lactone 5 in excellent ee, but limited only to activat-
ed substrates.3 Significant research effort has been devot-
ed to expanding the substrate scope of the [2+2] reaction.
tion, we recently reported the discovery of an active Lewis
acid–Lewis base (LA*–LB*) bifunctional catalyst 6
(Figure 1).7,8 We synthesized the ( )-Co(II)–LB* bifunc-
tional catalyst 6 from the ( )-diaminopropionic acid, and
demonstrated the LB*-dependent asymmetric induction
concept.7,9 We have also developed an empirical model
for predicting the R/S absolute stereochemistry of the
LA*–LB* catalyzed reactions.9 Herein, we report a highly
enantioselective [2+2] reaction catalyzed by a Co(III)-
based LA*–LB* bifunctional catalyst that displays
remarkable rate acceleration. The tethered LA*–LB*
bifunctional catalyst promotes the formation of enantio-
O
O–
C
+
Q*
CH2
OMe
1
2
N
Q*
Cl3CCHO
HO
(3)
N
O
O–
O
O
Cl3C
Q+*
quinidine (Q*)
4
Cl3C
5
Scheme 1 The catalytic cycle of the Wynberg reaction
SYNLETT 2009, No. 10, pp 1675–1679
x
x
.x
x
.2
0
0
9
Advanced online publication: 02.06.2009
DOI: 10.1055/s-0029-1217332; Art ID: Y01209ST
© Georg Thieme Verlag Stuttgart · New York

1676
S. Chidara, Y.-M. Lin
CLUSTER
Table 1 Initial Reaction Optimization Studies
LB*
OMe
Entrya
LA*–LB*
catalyst (mol%)
Reaction
time (h)
Yield
(%)b
ee
(8)c
N
••
1
2
3
4
5
6
6 (10)
9 (10)
10 (5)
10 (5)
10 (5)
9 (5)
12
6
5–6
45
65
82
–
–
O
N
planar LA*
N
O
12
–
N
12
>99%
>99%
>99%
–
Co
12
O
t-Bu
t-Bu
O
8 min
2
t-Bu
t-Bu
( )-Co(II)–LB*
6
a Reaction concentration [7] = 0.1 M; ketene was generated either
from acetyl chloride/Hünig’s base in situ (entries 1–4) or via pyrolysis
of acetone (entries 5 and 6). For entry 3, acetyl chloride was added
slowly (3 h) to the reaction and the reaction was stirred at –78 °C for
12 h; For entry 4, acetyl chloride was added very slowly (6 h) to the
reaction, which was stirred at –78 °C for 12 h. For entry 5, ketene gas
was bubbled into the reaction. See Experimental Section for details.
b Isolated yields (entries 3–5), except for entries 1 and 2, where con-
version% was estimated by crude 1H NMR.
Figure 1 A salen-Co(II) based LA*–LB* bifunctional catalyst
O
CHO
OBn
O
LA*–LB*
+
C O
H2C
BnO
CH2Cl2, –78 °C
1
7
8
c The ee was determined by chiral HPLC.
Scheme 2
mol%) produced little conversion of the aldehyde (entry
2, Table 1). In the low conversion reactions, competing
side reactions dominated to produce the undesired ketene
dimers. Taken together, these initial results suggested that
a more active bifunctional catalyst is necessary in order to
suppress the background reactions.
merically pure (>99% ee) b-lactones rapidly from alde-
hydes and ketene, with reaction times ranging from
minutes to one hour.
Our initial effort was focused on expanding the substrate
scope of the [2+2] cycloaddition reaction catalyzed by the
bifunctional catalyst 6. We employed enolizable 3-benzyl-
oxypropanal (7) as the substrate for initial optimization
studies (Scheme 2). The Co(II)-based LA*–LB* bifunc-
tional catalyst 6 proved less active for aldehyde 7, in spite
of many attempts. When ketene 1 was generated slowly in
situ from acetyl chloride and Hünig’s base,10 catalyst 6
(10 mol%) gave only 6% conversion of the reaction after
12 hours at –78 °C (entry 1, Table 1). The (S)-Co(II)–LB*
catalyst 9 (LB* = quinine) was subsequently synthesized
from the corresponding ligand, which was derived from
the (S)-diaminopropionic acid linker, and anhydrous
CoCl2 as a light-brown powder, using a modified proce-
dure. However, the (S)-Co(II)–LB* bifunctional catalyst
9 did not show an improvement in catalytic activity for al-
dehyde 7. Employing the (S)-Co(II)–LB* catalyst 9 (10
Inspired by Jacobsen’s seminal work on hydrolytic kinetic
resolution of epoxides catalyzed by Co–salen complex-
es,11 we decided to oxidize the metal in catalyst 9 from
Co(II) to Co(III). We reasoned that the Co(III)-based bi-
functional catalyst 10 should be more active, because Ja-
cobsen’s Co(III)–salen complex displays enhanced Lewis
acidity over its Co(II) analog.11 Indeed, after oxidizing the
Co(II) in catalyst 9 to Co(III) using AgSbF6,12 we ob-
served an improved catalytic activity (Scheme 3). The
Co(III)-based bifunctional catalyst 10 (5 mol%) promoted
the [2+2] reaction to produce the desired b-lactone 8 in
45–65% yields and >99% ee (entries 3 and 4, Table 1),
when ketene was generated in situ by slowly adding (via
a syringe pump) acetyl chloride to the reaction containing
OMe
OMe
N
N
O
O
O
O
N
N
AgSbF6
CH2Cl2, r.t.
(S)
N
N
N
N
Co+
Co
O
t-Bu
O
t-Bu
t-Bu
O
t-Bu
O
–
SbF6
t-Bu
t-Bu
t-Bu
t-Bu
(S)-Co(III)–LB* (10)
(S)-Co(II)–LB* (9)
Scheme 3
Synlett 2009, No. 10, 1675–1679 © Thieme Stuttgart · New York

CLUSTER
Reaction Rate Acceleration via Asymmetric Bifunctional Catalysis (ABC)
1677
Hünig’s base. It is important to add the acetyl chloride
methylene chloride solution over a period of six hours in
order to produce the desired b-lactone in good yields. In
contrast, regular drop-wise addition of acetyl chloride to
the reaction gave very little conversions. The isolated
ketene dimer by-product is presumably produced from the
reaction between the unreactive ketene and the ammoni-
um enolate species.
Table 2 Reaction Rate Acceleration Enabled by Tethered Lewis
Acid–Lewis Base Bifunctional Catalysis
Entrya
R (11)
Time
20 min
20 min
20 min
20 min
20 min
1 h
Yield 12 (%)b ee% (R/S)c
1
2
3
4
5
6
7
8
3-FC6H4-
3-ClC6H4-
2-ClC6H4-
2-FC6H4-
PhCH2-
87
97
95
87
96
96
74
71
>99 (S)
>99 (S)
>99 (S)
>99 (S)
>99 (R)
>99 (R)
>99 (R)
>99 (R)
In addition to the variable isolated yields (entries 3 and 4,
Table 1), employing the acetyl chloride/Hünig’s base pro-
tocol for generating the ketene in situ has two apparent
limitations in the LA*–LB* catalyzed enantioselective
cyclization reaction. First, ketene formation from the
acetyl chloride could be the rate-determining step. This
possibility would diminish the catalytic efficacy of the
LA*–LB* bifunctional catalyst. Second, the chloride an-
ion formed during the reaction could coordinate to the
Co(III), sequestering the cationic Co(III) catalytic species
into a stable hexacoordinate complex. In order to avoid
the pre-equilibrium ketene-forming step that limits the
overall reaction rate, we decided to employ Wynberg’s
protocol3 that utilizes pure ketene in the LA*–LB* cata-
lyzed reaction. Employing pure ketene in the reaction
would eliminate the competitive side reaction between the
ammonium enolate and the acetyl chloride. Without gen-
erating the chloride anion during the reaction, its coordi-
nation to the Co(III) would be avoided. Thus, it would
prevent converting the LA* from the cationic Co(III) into
a less Lewis acidic species.
PhCH2CH2-
n-C6H13-
n-C11H23-
1 h
1 h
a All reactions were carried out in 1 mmol scale, [11] = 0.1 M, ketene
was generated by pyrolysis of acetone.
b Isolated yield.
c The ee was determined by chiral HPLC and the R/S-configuration of
the b-lactones 12 were established experimentally.
The ensuing substrate scope studies revealed that the
Co(III)-based LA*–LB* bifunctional catalyst 10 was ap-
plicable to both aromatic and enolizable aliphatic alde-
hydes (Scheme 4, Table 2). We carried out the LA*–LB*
catalyzed [2+2] reaction in 0.1 M substrate concentra-
tions. The catalyst (5 mol%) promoted the reaction rapid-
ly at –78 °C after ketene (~2–3 equiv) was bubbled into
the methylene chloride solution. Halogenated aromatic al-
dehydes (entries 1–4) and phenylacetaldehyde (entry 5)
gave complete reactions in 20 minutes, furnishing the cor-
responding b-lactones 12 in excellent yields and >99% ee.
For the other enolizable aliphatic aldehydes examined, the
reaction was complete within one hour and afforded the
corresponding b-lactones 12 in excellent yields and >99%
ee (entries 6–8). The absolute configurations of b-lactones
12 were established experimentally, and all were consis-
tent with those predicted from our empirical model.9
In addition, pure ketene can be generated conveniently
from inexpensive acetone via pyrolysis, through a modi-
fied ketene lamp.13 Remarkably, after the ketene gas was
bubbled into the reaction at –78 °C, the Co(III)-derived
bifunctional catalyst 10 (5 mol%) promoted the reaction
rapidly. The reaction was complete within eight minutes,
affording the b-lactone 8 in 82% yield and >99% ee (entry
5). The R-configuration of the b-lactone 8 was established
experimentally. It can be noted that the correct configura-
tion is in agreement with that assigned from our empirical
model.9 In contrast, the (S)-Co(II)-based bifunctional cat-
alyst 9 proved to be inactive for the same reaction, under
similar reaction conditions (entry 6). Taken together,
these initial studies suggested that the enhanced Lewis
acidity is the key for a very active LA*–LB* bifunctional
catalyst, which is essential for the unprecedented rate ac-
celeration. In addition, it is important to employ pure
ketene, rather than the acetyl chloride/Hünig’s base as the
ketene source in the reaction, in order to attain the desired
rate acceleration.
We propose an open transition-state model intermediate
13 to account for the intramolecular bifunctional catalytic
cycle (Scheme 5). The LB* moiety of catalyst 10 converts
the ketene into an ammonium enolate, and delivers it to
the Co(III)-activated aldehyde in an intramolecular man-
ner. The resulting Co(III)-aldolate 14 lactonizes to furnish
b-lactone 12 and regenerate catalyst 10. The rapid catalyst
turnover is indicative of a weak aldolate–Co(III) interac-
tion, thus ensuring the catalytic cycle. Because the LA*
coordination sites in catalyst 10 are openly accessible for
substrates, the excellent ee of the reaction is consistent
with the LB*-dependent asymmetric induction concept.7,9
CH4
O
O
O
O
O
(S)-Co(III)–LB* 10 (5 mol%)
C
+
R
H
CH2Cl2, –78 °C
20 min to 1 h
CH2
R
11
12
1
Scheme 4
Synlett 2009, No. 10, 1675–1679 © Thieme Stuttgart · New York

1678
S. Chidara, Y.-M. Lin
CLUSTER
Ar
Ar
O
O
O
R
N+
N+
R
O
O
H
t-Bu
t-Bu
O
12
R
O
O
CH2=C=O
1
O
N
–O
N
Co+
O
O
N
O
N
O
LA*–LB* 10
LA*–LB* 10
t-Bu
Co
–
SbF6
t-Bu
RCHO
11
t-Bu
t-Bu
t-Bu
t-Bu
13
14
Scheme 5 An intramolecular asymmetric bifunctional catalysis working model
13C NMR (100 MHz, CDCl3): d = 168.2, 137.8, 128.4, 127.8, 127.6,
It is thus not surprising that the stereochemistry of the
LA*–LB* catalyzed [2+2] reaction is predictable.9
73.0, 69.1, 65.7, 43.1, 34.7.
IR (neat): 1825.4, 1191.1 cm–1.
In summary, we have discovered a Co(III)-derived LA*–
LB* bifunctional catalyst that is highly active for the
catalytic, enantioselective [2+2] cycloaddition reaction
between aldehydes and unsubstituted ketene, with unprec-
edented reaction rate accelerations and enantioselectivity.
The current LA*–LB* bifunctional catalyst rapidly con-
verts both aromatic and aliphatic aldehydes into the corre-
sponding b-lactones in excellent yields. Because chiral b-
lactones can be readily converted into the corresponding
b-hydroxy esters (i.e. acetate aldols) with retention of
configurations via alcoholysis, the LA*–LB* catalyzed
[2+2] reaction offers an invaluable alternative to the cata-
lytic, asymmetric acetate aldol reaction, without generat-
ing the required silyl ketene acetals.14 In addition, the
remarkable rate acceleration attained by the current LA*–
LB* bifunctional catalyst suggests a general strategy that
can be extended to organocatalysis15 for speeding up the
reactions. Applications of the Co(III)-derived LA*–LB*
bifunctional catalyst to other reactions, particularly those
amenable for Lewis base catalysis16 for rate acceleration,
are currently underway in our laboratory and we will re-
port our results in due course.
Chiral HPLC analysis of b-lactone 8 gave a single peak at 15.0 min
(> 99% ee). Under the same HPLC conditions, a racemic sample
gave two well-resolved peaks. HPLC conditions: HPLC
column = CHIRALCEL OD-H (0.46 × 25 cm); i-PrOH–hexanes,
15:85 (v/v); flow rate = 1.0 mL/min; UV detection: 210 nm.
Table 3 contains the HPLC conditions used to analyze the samples
listed in Table 2.
Table 3 Summary of HPLC Conditions Corresponding to the En-
tries in Table 2
Entry i-PrOH–hexanes mobile phase TR
UV detection l
(nm)
(v/v) and flow rate (mL/min) (min)
1a
2a
3a
4a
5b
6b
7c
8d
10:90 (1.0)
10:90 (1.0)
20:80 (0.5)
20:80 (0.5)
10:90 (1.0)
10:90 (1.0)
4:96 (1.0)
3:97 (1.0)
6.6
7.7
260
210
220
260
210
210
210
210
9.7
8.9
13.3
16.3
8.0
12.4
LA*–LB* Catalyzed Asymmetric [2+2] Cycloaddition Reac-
tion; Typical Procedure
a HPLC analysis was carried out on their corresponding b-hydroxy
methyl esters.
(R)-4-(2-Benzyloxyethyl)oxetan-2-one (8): To a solution of catalyst
9·2HCl (49 mg, 0.05 mmol) in methylene chloride (2.0 mL) at r.t.,
was added AgSbF6 (52 mg, 0.15 mmol). The resulting dark-brown
mixture was stirred at r.t. for 1.5 h, followed by the addition of me-
thylene chloride (8.0 mL), diisopropylethylamine (0.10 mL, 0.61
mmol), and aldehyde 7 (164 mg, 1.0 mmol). The solution was
cooled to –78 °C and ketene gas (~2–3 equiv) generated via pyro-
lysis of acetone was bubbled into the reaction mixture for 8 min to
give a complete reaction, as indicated by TLC. The reaction was
quenched with sat. NaHCO3 at –78 °C, warmed up to r.t., and ex-
tracted with methylene chloride. The combined organic phases were
washed with brine, dried (Na2SO4), filtered, concentrated and sepa-
rated by flash column chromatography on silica gel (hexanes–
EtOAc, 16:1→8:1→4:1) to give b-lactone 8.
b HPLC analysis was carried out on the b-lactones.
c HPLC analysis was carried out on the (S)-O-methylmandelate of its
b-hydroxy methyl ester.
d HPLC analysis was carried out on the (R)-O-methylmandelate of its
b-hydroxy methyl ester.
Acknowledgment
Acknowledgment is made to the donors of the American Chemical
Society Petroleum Research Fund (PRF #48739-ND1) for support
of this research. This material is also based on work partially sup-
ported by the National Science Foundation. We thank the undergra-
duate teaching laboratory of our department for the use of HPLC
instruments.
Yield: 168 mg (82%); oil.
1H NMR (400 MHz, CDCl3): d = 7.37–7.27 (m, 5 H), 4.68 (m, 1 H),
4.50 (s, 2 H), 3.62 (m, 2 H), 3.53 (dd, J = 16.4, 5.6 Hz, 1 H), 3.17
(dd, J = 16.4, 4.4 Hz, 1 H), 2.11 (m, 2 H).
Synlett 2009, No. 10, 1675–1679 © Thieme Stuttgart · New York

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Reaction Rate Acceleration via Asymmetric Bifunctional Catalysis (ABC)
1679
M.; Hayashi, T. J. Am. Chem. Soc. 1986, 108, 6405.
(d) Josephsohn, N. S.; Kuntz, K. W.; Snapper, M. L.;
References and Notes
(1) For selected reviews on b-lactones and their synthetic
applications, see: (a) Pommier, A.; Pons, J.-M. Synthesis
1993, 441. (b) Yang, H. W.; Romo, D. Tetrahedron 1999,
55, 6403. (c) Schneider, C. Angew. Chem. Int. Ed. 2002, 41,
744; Angew. Chem. 2002, 114, 771. (d) Wang, Y.;
Tennyson, R. L.; Romo, D. Heterocycles 2004, 64, 605.
(2) For selected reviews, see: (a) Tidwell, T. T. Eur. J. Org.
Chem. 2006, 563. (b) Orr, R. K.; Calter, M. A. Tetrahedron
2003, 59, 3545. For examples of b-lactone formation from
silylketene, see: (c) Evans, D. A.; Janey, J. M. Org. Lett.
2001, 3, 2125. (d) Forslund, R. E.; Cain, J.; Colyer, J.;
Doyle, M. P. Adv. Synth. Catal. 2005, 347, 87.
Hoveyda, A. H. J. Am. Chem. Soc. 2001, 123, 11594.
(e) DiMauro, E. F.; Kozlowski, M. C. Org. Lett. 2001, 3,
3053. (f) Ichikawa, E.; Suzuki, M.; Yabu, K.; Albert, M.;
Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2004, 126,
11808. (g) France, S.; Shah, M. H.; Weatherwax, A.; Wack,
H.; Roth, J. P.; Lectka, T. J. Am. Chem. Soc. 2005, 127,
1206. (h) Fennie, M. W.; Dimauro, E. F.; O’Brien, E. M.;
Annamalai, V.; Kozlowski, M. C. Tetrahedron 2005, 61,
6249.
(9) Lin, Y.-M.; Li, Z.; Boucau, J. Tetrahedron Lett. 2007, 48,
5275.
(10) For examples of generating ketene from acyl halides and
Hünig’s base in situ, see ref 2a and 5.
(11) (a) Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.; Jacobsen,
E. N. Science 1997, 277, 936. (b) Jacobsen, E. N. Acc.
Chem. Res. 2000, 33, 421.
(12) For an example of oxidizing a Co(II)–salen complex to the
corresponding Co(III)–salen complex using AgSbF6, see:
Hutson, G. E.; Dave, A. H.; Rawal, V. H. Org. Lett. 2007,
9, 3869.
(13) Williams, J. W.; Hurd, C. D. J. Org. Chem. 1940, 5, 122.
(14) For selected examples of catalytic asymmetric acetate aldol
reactions, see: (a) Mikami, K.; Matsukawa, S. J. Am. Chem.
Soc. 1994, 116, 4077. (b) Carreira, E. M.; Singer, R. A.;
Lee, W. J. Am. Chem. Soc. 1994, 116, 8837. (c) For an
overview, see: Carreira, E. M.; Fettes, A.; Marti, C. In
Organic Reactions, Vol. 67; Overman, L. E., Ed.; Wiley &
Sons: New York, 2006, 1–216; and references cited therein.
(15) For selected reviews on organocatalysis, see: (a) List, B.
Chem. Rev. 2007, 107, 5413. (b) MacMillan, D. W. C.
Nature 2008, 455, 304.
(3) (a) Wynberg, H.; Staring, E. G. J. J. Am. Chem. Soc. 1982,
104, 166. (b) Wynberg, H.; Staring, E. G. J. J. Org. Chem.
1985, 50, 1977.
(4) Cortez, G. S.; Tennyson, R. L.; Romo, D. J. Am. Chem. Soc.
2001, 123, 7945.
(5) (a) Nelson, S. G.; Zhu, C.; Shen, X. J. Am. Chem. Soc. 2004,
126, 14. (b) Zhu, C.; Shen, X.; Nelson, S. G. J. Am. Chem.
Soc. 2004, 126, 5352. (c) Calter, M. A.; Tretyak, O. A.;
Flascheriem, C. Org. Lett. 2005, 7, 1809.
(6) (a) Wilson, J. E.; Fu, G. C. Angew. Chem. Int. Ed. 2004, 43,
6358; Angew. Chem. 2004, 116, 6518. (b) Gnanadesikan,
V.; Corey, E. J. Org. Lett. 2006, 8, 4943. (c) Kull, T.;
Peters, R. Adv. Synth. Catal. 2007, 349, 1647. (d) Kull, T.;
Peters, R. Angew. Chem. Int. Ed. 2008, 47, 5461; Angew.
Chem. 2008, 120, 5541. (e) He, L.; Lv, H.; Zhang, Y.-R.;
Ye, S. J. Org. Chem. 2008, 73, 8101.
(7) Lin, Y.-M.; Boucau, J.; Li, Z.; Casarotto, V.; Lin, J.;
Nguyen, A. N.; Ehrmantraut, J. Org. Lett. 2007, 9, 567.
(8) For selected reviews on tethered Lewis acid–Lewis base
bifunctional catalysts, see: (a) Paull, D. H.; Abraham, C. J.;
Scerba, M. T.; Alden-Danforth, E.; Lectka, T. Acc. Chem.
Res. 2008, 41, 655. (b) Kanai, M.; Kato, N.; Ichikawa, E.;
Shibasaki, M. Synlett 2005, 1491. For selected examples of
tethered bifunctional catalysts, see: (c) Ito, Y.; Sawamura,
(16) For a recent review on Lewis base catalysis, see: Denmark,
S. E.; Beutner, G. L. Angew. Chem. Int. Ed. 2008, 47, 1560;
Angew. Chem. 2008, 120, 1584.
Ar
bifunctional
catalysis
O
R
N+
O
O
LA*–LB*
(5 mol%)
H
O
O
t-Bu
O
N
+
–78 °C
–O
R
H
H
R
O
C
N
O
Co
>99% ee
t-Bu
O
–
SbF6
C
H
R = aryl and alkyl
t-Bu
t-Bu
Synlett 2009, No. 10, 1675–1679 © Thieme Stuttgart · New York

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