Organocatalytic asymmetric fluorination/semipinacol rearrangement: An efficient approach to chiral β-fluoroketones

Full text of DOI:10.1002/chem.201202444

DOI: 10.1002/chem.201202444
Organocatalytic Asymmetric Fluorination/Semipinacol Rearrangement: An
Efficient Approach to Chiral b-Fluoroketones
[
a]
[a]
[a]
[a]
Zhi-Min Chen, Bin-Miao Yang, Zhi-Hua Chen, Qing-Wei Zhang,
[
b]
[a, b]
Min Wang, and Yong-Qiang Tu*
[
10]
Chiral fluorinated molecules have attractive properties for
metric fluorination/semipinacol rearrangement,
however,
[1]
agricultural, medicinal, and material applications. There-
fore, the introduction of carbon–fluorine bonds in an asym-
metric manner is of great importance in modern synthetic
chemistry, and the development of methodologies that ach-
ieve this transformation are in high demand. During the
past years, tremendous efforts have been made in develop-
ing methods for the asymmetric formation of carbon–fluo-
a suitable catalytic method has yet to be reported.
In the past years, cinchona alkaloids and their derivatives,
which are some of the most important organocatalysts, have
been extensively studied. Various enantioselective transfor-
[11]
mations promoted by these catalysts have been achieved.
Recently, our research group and that of others have report-
ed some examples of asymmetric bromination/semipinacol
rearrangement reactions that are catalyzed by cinchona-al-
kaloid derivatives. In light of our previous results, com-
bined with our long-standing interest in semipinacol-rear-
[2]
rine bonds; many of these methods focus on the catalytic
[3]
[12]
asymmetric fluorination of 1,3-dicarbonyl compounds and
[4]
carbonyl compounds. In contrast, very few methods involv-
ing the catalytic asymmetric fluorination of olefins have
[13,14]
rangement reactions,
we hypothesized that the fluorina-
[5,6]
been described.
There has been significant progress in
tion/semipinacol rearrangement reaction could also be cata-
lyzed by cinchona-alkaloid derivatives in an asymmetric
manner (Scheme 2). Herein, we present our preliminary re-
sults on this reaction.
the development of addition reactions of olefins involving
the heavier halogen atoms (X=Br, Cl, and I), a series of
transformations that are some of the most powerful in or-
[7]
ganic chemistry; the catalytic enantioselective fluorination
of olefins remains a challenge. The fluorination/semipinacol
rearrangement, which is initiated by fluorination of the
[8]
double bond, is a straightforward strategy for the prepara-
tion of b-fluorocarbonyl compounds, which are potentially
[9]
useful compounds for fluorine chemistry. Moreover, two
adjacent stereocenters, one of which is quaternary, are
formed simultaneously through this rearrangement, which
uses simple allylic alcohols as starting materials (Scheme 1).
In 2005, our research group reported a noncatalytic asym-
Scheme 2. A design for a catalytic enantioselective fluorination/semipina-
col rearrangement reaction.
We began our investigation using 2-oxa allylic alcohol 1a
as a model substrate. A careful survey of cinchona-alkaloid-
derived catalysts was conducted for the fluorination/semipi-
nacol rearrangement reaction (Table 1). Among these cata-
lysts, hydroquinidine-2,5-diphenyl-4,6-pyrimidinediyl diether
(
(DHQD) PYR), 3c) was the most effective catalyst and
2
gave 2a in 32% yield and with an ee value of 50% (Table 1,
entries 1–4). Next, using 3c as the catalyst, various inor-
Scheme 1. Halogenation/semipinacol rearrangement reaction.
[15]
ganic bases, such as Na CO , Cs CO , and K CO , were in-
2
3
2
3
2
3
vestigated as additives (Table 1, entries 5–7). Remarkably, it
was found that the use of K CO led to a reaction of en-
[
a] Z.-M. Chen, B.-M. Yang, Z.-H. Chen, Q.-W. Zhang, Y.-Q. Tu
State Key Laboratory of Applied Organic Chemistry and
Department of Chemistry, Lanzhou University
Lanzhou 730000 (P. R. China)
2
3
hanced enantioselectivity (62% ee). More encouragingly,
when the reaction temperature was lowered to 08C, the
enantioselectivity increased to value of 72% (Table 1,
entry 8). To further improve the yield and the enantioselec-
tivity, we screened the solvent, the nature of which strongly
affected both the reactivity and the enantioselectivity. The
use of tetrahydrofuran (THF) as a solvent led to no reac-
[
b] M. Wang, Y.-Q. Tu
College of Material, Chemistry and Chemical Engineering
Hangzhou Normal University, Hangzhou, 310036 (P. R. China)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201202444.
12950
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 12950 – 12954

COMMUNICATION
[
a]
Table 1. Optimization of the asymmetric reaction.
Table 2. Asymmetric
fluorination
reaction
using
catalyst
[
a]
(
2
DHQD) PYR.
[
b]
[c]
Entry
1
Substrate
Yield [%]
ee [%]
1
2
1a: n=1, R =C
1a: n=1, R =C
1b: n=1, R =4-F-C
6 4
1c: n=1, R =4-Cl-C H , R =H
1d: n=1, R =4-Br-C
1e: n=1, R =3-F-C
3 2 6 3
1 f: n=1, R =3,5-(CH ) C H , R =H
1g: n=1, R =2-naphthyl, R =H
1h: n=1, R =2-thienyl, R =H
1i: n=1, R =C
1j: n=0, R =C
1k: n=0, R =4-F-C H , R =H
6 4
6
6
H
H
5
5
, R =H
56
53
41
34
39
41
76
54
76
47
66
48
93
92
92
79
71
93
66
71
38
86
85
81
[
d]
1
2
2
3
4
5
6
7
8
9
, R =H
1
2
6
H
4
, R =H
[
[
[
e]
e]
e]
1
2
1
2
6
H
4
, R =H
, R =H
1
2
6
H
4
[
b]
[c]
Entry
Cat.
T [8C]
Solvent
Additive
Yield [%]
ee [%]
[e]
1
2
1
2
1
2
3
4
5
6
7
8
9
1
1
1
1
1
3a
3b
3c
3d
3c
3c
3c
3c
3c
3c
3c
3c
3c
3c
RT
RT
RT
RT
RT
RT
RT
0
0
0
0
-10
-10
-10
CH
CH
CH
CH
CH
CH
CH
CH
THF
CHCl
DCE
DCE
DCE
DCE
3
3
3
3
3
3
3
3
CN
CN
CN
CN
CN
CN
CN
CN
–
–
–
–
27
25
32
20
30
35
36
44
–
28
48
52
56
54
17
10
50
16
54
54
62
72
–
81
86
90
93
93
[
e]
1
2
1
2
10
11
12
6
H
5, R =Me
[f]
1
2
6
H
5
, R =H
1
2
Na
Cs
2
CO
CO
3
2
3
[
a] All reactions, unless noted otherwise, were performed with 0.1 mmol
of 1, 0.12 mmol of K CO , and 0.02 mmol of (DHQD) PYR in 1 mL of
,2-dichloroethane at À108C. NFSI (0.12 mmol) was added in six por-
tions. [b] Yield of isolated product. [c] Determined by HPLC analysis
using a chiral stationary phase. [d] Using 0.1 equiv of (DHQD) PYR.
e] The reaction was carried out at 08C.
K
K
K
K
K
K
K
K
2
CO
CO
CO
CO
CO
CO
CO
CO
3
2
3
2
2
2
2
2
2
2
2
3
1
3
3
3
3
3
3
0
1
2
3
4
3
2
[
[
[
d]
e]
products with lower ee values (Table 2, entries 4 and 5). The
use of 3-fluorophenyl-substituted allylic alcohol 1e led to
enantioselectivity that was similar to that of the-4-fluoro-
phenyl substituted substrate (Table 2, entry 6). It was found
that the presence of more than one substituent on the
phenyl group adversely affected the enantioselectivity
[
a] All reactions, unless otherwise noted, were performed with 0.1 mmol
of 1a in 1 mL of solvent. [b] Yield of isolated product. [c] Determined by
HPLC analysis using a chiral stationary phase. [d] 1.2 equiv of NFSI was
added in six portions. [e] Using 6.0 equiv of K CO . [f] the sense of asym-
2 3
metric induction was opposite that observed in reactions associated with
other entries in this table.
(
Table 2, entry 7). Additionally, the sterically demanding 2-
tion, whereas the use of the chlorinated solvent, 1,2-di-
chloroethane (DCE), led to much improved enantioselectiv-
ity, 86% ee (Table 1, entries 9–11). To our delight, when the
reaction temperature was further lowered to À108C, the
enantioselectivity increased further (90% ee; Table 1,
entry 12). Considering that a background reaction might be
influencing the result, we added N-fluorobenzenesulfoni-
mide (NFSI) portionwise, a condition that further improved
the enantioselectivity (93% ee; Table 1, entry 13). In addi-
tion, no improvement in enantioselectivity and yield was ob-
served when a large excess of K CO was used (Table 1,
naphthyl-substituted substrate also gave moderate enantio-
selectivity (Table 2, entry 8). Unfortunately, heterocycle-sub-
stituted allylic alcohols were not good substrates for the cat-
alytic asymmetric reaction (Table 2, entry 9). To further
expand the substrate scope, a substrate with a gem-dimethyl
substituted C5 position within the dihydropyranyl ring was
also examined and when used in the reaction it led to the
corresponding product in moderate yield with a high ee val-
ue (Table 2, entry 10). Finally, the reaction of two substrates
containing dihydrofuranyl moieties also gave the desired
products with high ee values (Table 2, entries 11 and 12).
Notably, the absolute configuration of the product 2a was
determined by X-ray crystallography analysis of its deriva-
tive, 4a (see the Supporting Information for further de-
2
3
entry 14).
With optimized reaction conditions established, various 2-
oxa allylic alcohols (1b–k) were subjected to the fluorina-
tion/semipinacol rearrangement reaction. All substrates af-
forded the desired chiral b-fluoroketone derivatives in mod-
erate to good yields with moderate to excellent levels of
enantioselectivity (Table 2). In comparison to the reaction
of model substrate 1a, the reaction of a substrate bearing a
halogen substituent at the para position of the phenyl
moiety showed lower levels of enantioselectivity (Table 2,
entries 3–5). When 4-fluorophenyl-substituted allylic alcohol
[16]
tails).
Because enantiomers generally have disparate biological
activities, convenient access to both enantiomers is distinctly
important in asymmetric catalysis. To our delight, the reac-
tion of 1a with 20 mol% hydroquinine 2,5-diphenyl-4,6-pyri-
midinediyl diether ((DHQ) PYR) and NFSI in the presence
2
of K CO in 1,2-dichloroethane at À108C gave 2a’ (ent-2a)
2
3
in 46% yield with 89% ee (Table 3, entry 1). Next, the same
1
b was used, a similarly high level of enantioselectivity was
substrates that were used above with (DHQD) PYR (3c) as
2
observed (Table 2, entry 3). However, substrates containing
either 4-chlorophenyl or 4-bromophenyl substituents gave
the catalyst were subjected to the standard reaction condi-
tions using (DHQ) PYR, thus giving the products 2a’–k’,
2
Chem. Eur. J. 2012, 18, 12950 – 12954
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
12951

Y.-Q. Tu et al.
[
a]
Table 3. Asymmetric fluorination reaction using catalyst (DHQ)
2
PYR.
cause a series of chiral b-fluoroketones, which contain vari-
ous substituents and oxygen-containing rings of various size,
can be prepared from simple allylic alcohols. Moreover,
both enantiomers of the products were readily obtained
with moderate to excellent ee values. Further investigations
are underway to determine the mechanism.
[
b]
[c]
Entry Substrate
Yield [%]
ee [%]
1
2
1
2
3
4
5
6
7
8
9
1
1
1
1
1a: n=1, R =C
6
6
6
H
H
H
5
5
5
, R =H
46
46
42
38
31
29
35
89
90
90
86
77
70
87
63
68
36
77
86
84
[
[
d]
e]
1
2
1a: n=1, R =C
, R =H
Experimental Section
1
2
1a: n=1, R =C
, R =H
1
2
1b: n=1, R =4-F-C
6
H
4
, R =H
[
[
[
[
f]
f]
f]
f]
1
2
General procedure:
(DHQ) PYR (20 mol%) and NFSI (0.02 mmol) in 1,2-dichloroethane
(0.5 mL) was stirred under argon at RT for 10 min. K CO (0.12 mmol)
2
A mixture of (DHQD) PYR (20 mol%) or
6 4
1c: n=1, R =4-Cl-C H , R =H
1
2
1d: n=1, R =4-Br-C
6
H
4
, R =H
, R =H
2
1
2
1e: n=1, R =3-F-C
6
H
4
2
3
1
2
was then added to the solution, and the reaction mixture was stirred for
10 min at À108C. A solution of the 2-oxa allylic alcohol 1a (0.1 mmol) in
1,2-dichloroethane (0.5 mL) was added to the mixture and the resulting
mixture was stirred at the same temperature. NFSI (0.1 mmol) was added
in five portions (0.02 mmol every 8 h). After the substrate was complete-
ly consumed (as detected using thin-layer chromatography), the reaction
mixture was directly subjected to column chromatography using silica gel
as the stationary phase and petroleum ether/ethyl acetate (125:1) as the
eluent to give the desired product.
3 2 6 3
1 f: n=1, R =3,5-(CH ) -C H , R =H 73
1
2
1g: n=1, R =2-naphthyl, R =H
44
58
42
54
33
[
f]
1
2
0
1
2
3
1h: n=1, R =2-thienyl, R =H
1
2
1i: n=1, R =C
6
H
5, R =Me
1
2
1j: n=0, R =C
6
H
5
, R =H
1
2
6 4
1k: n=0, R =4-F-C H , R =H
[
a] All reactions, unless noted otherwise, were performed with 0.1 mmol
of 1, 0.12 mmol of K CO , and 0.02 mmol of (DHQ) PYR in 1 mL of 1,2-
dichloroethane at À108C. NFSI (0.12 mmol) was added in six portions.
b] Yield of isolated product. [c] Determined by HPLC analysis using a
chiral stationary phase. [d] Cs CO was added instead of CO
e] Using 0.1 equiv of (DHQ) PYR. [f] The reaction was carried out at
8C.
2
3
2
[
2
3
K
2
3
.
[
0
2
Acknowledgements
We gratefully acknowledge financial support from the NSFC (Grant Nos.
2
1072085, 20921120404, 21102061, and 20972059), the National Basic Re-
search Program of China (“973” Program, Grant No. 2010CB833203),
111” Program of MOE, National S&T Major Project of China
2012ZX09201101—003), and scholarship award for excellent doctoral
which are the enantiomers of 2a–k, in moderate yields and
with moderate to high levels of enantioselectivity. In com-
parison to the products 2a–i, the products 2a’–i’ were ob-
tained with slightly lower ee values (Table 3, entries 1–11),
although, two substrates containing dihydrofuranyl moieties
were obtained with slightly higher ee values (Table 3, en-
tries 12 and 13). In addition, we also examined the effect of
Cs CO as an additive (instead of K CO ), which was also
“
(
student, No.86007.
Keywords: asymmetric catalysis
fluorination · organocatalysis · rearrangement
· cinchona alkaloids ·
2
3
2
3
examined in our initial optimization studies, and found that
the enantioselectivity was slightly higher in the reaction of
[
1] a) P. Kirsch, Modern Fluoroorganic Chemistry, Wiley-VCH, Wein-
heim, 2004; b) I. Ojima in Fluorine in Medicinal Chemistry and
Chemical Biology, Wiley-Blackwell, Chichester, 2009; c) H. Ibrahim,
A. Togni, Chem. Commun. 2004, 1147–1155; d) M. Oestreich,
Angew. Chem. 2005, 117, 2376–2379; Angew. Chem. Int. Ed. 2005,
1
a (90% ee; Table 3, entry 2). However, the use of Cs CO3
2
instead of K CO had a negative effect on the enantioselec-
2
3
tivity for other substrates.
4
1
2
2
4, 2324–2327; e) N. Shibata, J. Synth. Org. Chem. Jpn. 2006, 64,
4–24; f) Y. Hamashima, M. Sodeoka, J. Synth. Org. Chem. Jpn.
007, 65, 1099–1107; g) K. Mꢁller, C. Faeh, F. Diederich, Science
007, 317, 1881–1886; h) K. L. Kirk, Org. Process Res. Dev. 2008,
Chiral b-fluoroketones are potentially useful synthons for
fluorine chemistry, and therefore, the investigation of a
large-scale reaction would be necessary to evaluate the syn-
thetic utility of the reaction. Accordingly, the rearrangement
of substrate 1a was carried out on a 1 mmol scale with cata-
lyst loading of 10 mol% and the desired product 2a was ob-
tained in 43% yield with an ee value of 90% (Scheme 3).
In summary, a novel asymmetric fluorination/semipinacol
rearrangement reaction that is catalyzed by cinchona-alka-
loid derivatives was developed. This reaction is valuable be-
12, 305–321; i) D. O’Hagan, Chem. Soc. Rev. 2008, 37, 308–319; j) S.
Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev.
2
l) X.-L. Qiu, X.-H. Xu, F.-L. Qing, Tetrahedron 2010, 66, 789–843.
2] For recent reviews on asymmetric fluorination reactions, see:
a) P. M. Pihko, Angew. Chem. 2006, 118, 558–561; Angew. Chem.
Int. Ed. 2006, 45, 544–547; b) Y. Hamashima, M. Sodeoka, Synlett
008, 37, 320–330; k) L. Hunter, Beilstein J. Org. Chem. 2010, 6, 38;
[
2
1
006, 1467–1478; c) G. K. S. Prakash, P. Beier, Angew. Chem. 2006,
18, 2228–2230; Angew. Chem. Int. Ed. 2006, 45, 2172–2174; d) C.
Bobbio, V. Gouverneur, Org. Biomol. Chem. 2006, 4, 2065–2075;
e) N. Shibata, T. Ishimaru, S. Nakamura, T. Toru, J. Fluorine Chem.
2
2
007, 128, 469–483; f) V. A. Brunet, D. OꢂHagan, Angew. Chem.
008, 120, 1198–1201; Angew. Chem. Int. Ed. 2008, 47, 1179–1182;
g) J.-A. Ma, D. Cahard, Chem. Rev. 2008, 108, PR1-PR43; h) T.
Furuya, C. A. Kuttruff, T. Ritter, Curr. Opin. Drug Discov. Devel.
2
008, 11, 803–819; i) M. Ueda, T. Kano, K. Maruoka, Org. Biomol.
Chem. 2009, 7, 2005–2012; j) S. Lectard, Y. Hamashima, M. Sodeo-
ka, Adv. Synth. Catal. 2010, 352, 2708–2732; k) T. Furuya, A. S.
Scheme 3. Asymmetric fluorination reaction on a 1 mmol scale.
12952
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 12950 – 12954

Asymmetric Fluorination/Semipinacol Rearrangement
COMMUNICATION
Kamlet, T. Ritter, Nature 2011, 473, 470–477; l) G. Valero, X. com-
panyꢃ, R. Rios, Chem. Eur. J. 2011, 17, 2018–2037; m) U. Hennecke,
Angew. Chem. 2012, 124, 4608–4610; Angew. Chem. Int. Ed. 2012,
2010, 39, 466–467; s) P. Kwiatkowski, T. D. Beeson, J. C. Conrad,
D. W. C. MacMillan, J. Am. Chem. Soc. 2011, 133, 1738–1741; t) E.-
M. Tanzer, W. B. Schweizer, M.-O. Ebert, R. Gilmour, Chem. Eur. J.
2012, 18, 2006–2013; u) S. Suzuki, Y. Kitamura, S. Lectard, Y. Ha-
mashima, M. Sodeoka, Angew. Chem. 2012, 124, 4659–4663; Angew.
Chem. Int. Ed. 2012, 51, 4581–4585.
5
1, 4532–4534.
[
3] a) L. Hintermann, A. Togni, Angew. Chem. 2000, 112, 4530–4533;
Angew. Chem. Int. Ed. 2000, 39, 4359–4362; b) Y. Hamashima, K.
Yagi, H. Takano, L. Tamꢄs, M. Sodeoka, J. Am. Chem. Soc. 2002,
[5] For catalytic methods for the asymmetric fluorination of olefins, see:
a) T. Fukuzumi, N. Shibata, M. Sugiura, S. Nakamura, T. Toru, J.
Fluorine Chem. 2006, 127, 548–551; b) T. Ishimaru, N. Shibata, T.
Horikawa, N. Yasuda, S. Nakamura, T. Toru, M. Shiro, Angew.
Chem. 2008, 120, 4225–4229; Angew. Chem. Int. Ed. 2008, 47, 4157–
4161; c) O. Lozano, G. Blessley, T. Martinez del Campo, A. L.
Thompson, G. T. Giuffredi, M. Bettati, M. Walker, R. Borman, V.
Gouverneur, Angew. Chem. 2011, 123, 8255–8259; Angew. Chem.
Int. Ed. 2011, 50, 8105–8109; d) V. Rauniyar, A. D. Lackner, G. L.
Hamilton, F. D. Toste, Science 2011, 334, 1681–1684; e) R. J. Phipps,
K. Hiramatsu, F. D. Toste, J. Am. Chem. Soc. 2012, 134, 8376–8379.
[6] For stoichiometric methods for the asymmetric fluorination of ole-
fins, see: a) N. Shibata, E. Suzuki, Y. Takeuchi, J. Am. Chem. Soc.
2000, 122, 10728–10729; b) D. Cahard, C. Audouard, J.-C. Plaque-
vent, N. Roques, Org. Lett. 2000, 2, 3699–3701; c) B. Greedy, J. M.
Paris, T. Vidal, V. Gouverneur, Angew. Chem. 2003, 115, 3413–
3416; Angew. Chem. Int. Ed. 2003, 42, 3291–3294; d) S. C. Wilkin-
son, O. Lozano, M. Schuler, M. C. Pacheco, R. Salmon, V. Gouver-
neur, Angew. Chem. 2009, 121, 7217–7220; Angew. Chem. Int. Ed.
2009, 48, 7083–7086.
1
24, 14530–14531; c) D. Y. Kim, E. J. Park, Org. Lett. 2002, 4, 545–
5
47; d) R. Frantz, L. Hintermann, M. Perseghini, D. Broggini, A.
Togni, Org. Lett. 2003, 5, 1709–1712; e) Y. Hamashima, H. Takano,
D. Hotta, M. Sodeoka, Org. Lett. 2003, 5, 3225–3228; f) P. Y. Toul-
lec, C. Bonaccorsi, A. Mezztti, A. Togni, Proc. Natl. Acad. Sci. USA
2
004, 101, 5810–5814; g) J.-A. Ma, D. Cahard, Tetrahedron: Asym-
metry 2004, 15, 1007–1011; h) N. Shibata, T. Ishimaru, T. Nagai, J.
Kohno, T. Toru, Synlett 2004, 1703–1706; i) Y. Hamashima, T.
Suzuki, H. Takano, Y. Shimura, M. Sodeoka, J. Am. Chem. Soc.
2
2
Commun. 2005, 1324–1326; l) Y. Hamashima, T. Suzuki, H. Takano,
Y. Shimura, Y. Tsuchiya, K. Moriya, T. Goto, M. Sodeoka, Tetrahe-
dron 2006, 62, 7168–7179; m) C. Bonaccorsi, M. Althaus, C. Becker,
A. Togni, A. Mezzetti, Pure Appl. Chem. 2006, 78, 391–396;
n) S. M. Kim, Y. K. Kang, K. S. Lee, J. Y. Mang, D. Y. Kim, Bull.
Korean Chem. Soc. 2006, 27, 423–425; o) S. Suzuki, H. Furuno, Y.
Yokoyama, J. Inanaga, Tetrahedron: Asymmetry 2006, 17, 504–507;
p) M. Perseghini, M. Massaccesi, Y. Liu, A. Togni, Tetrahedron
005, 127, 10164–10165; j) H. R. Kim, D. Y. Kim, Tetrahedron Lett.
005, 46, 3115–3117; k) L. Bernardi, K. A. Jørgensen, Chem.
2
006, 62, 7180–7190; q) M. Althaus, C. Becker, A. Togni, A. Mez-
[7] For selected reviews on asymmetric halogenation of olefins, see:
a) A. N. French, S. Bissmire, T. Wirth, Chem. Soc. Rev. 2004, 33,
354–362; b) G. Chen, S. Ma, Angew. Chem. 2010, 122, 8484–8486;
Angew. Chem. Int. Ed. 2010, 49, 8306–8308; c) A. Castellanos, S. P.
Fletcher, Chem. Eur. J. 2011, 17, 5766–5776; d) C. K. Tan, L. Zhou,
Y.-Y. Yeung, Synlett 2011, 1335–1339; e) U. Hennecke, Chem. Asian
J. 2012, 7, 456–465.
[8] a) M. D. Burkart, Z. Zhang, S.-C. Hung, C.-H. Wong, J. Am. Chem.
Soc. 1997, 119, 11743–11746; b) B.-M. Wang, Z.-L. Song, C.-A. Fan,
Y.-Q. Tu, W.-M. Chen, Synlett 2003, 1497–1499.
[9] a) R. D. Chambers, M. Parsons, G. Standford, R. Bowden, Chem.
Commun. 2000, 959–960; b) J. A. Miller, G. M. Ullah, G. M. Welsh,
P. Mallon, Tetrahedron Lett. 2001, 42, 2729–2731.
[10] M. Wang, B.-M. Wang, L. Shi, Y.-Q. Tu, C.-A. Fan, S.-H. Wang, X.-
D. Hu, S.-Y. Zhang, Chem. Commun. 2005, 5580–5582.
zetti, Organometallics 2007, 26, 5902–5911; r) T. Suzuki, T. Goto, Y.
Hamashima, M. Sodeoka, J. Org. Chem. 2007, 72, 246–250; s) K.
Shibatomi, Y. Tsuzuki, S. Nakata, Y. Sumikawa, S. Iwasa, Synlett
2
007, 551–554; t) Y. K. Kang, M. J. Cho, S. M. Kim, D. Y. Kim, Syn-
lett 2007, 1135–1138; u) K. Moriya, Y. Hamashima, M. Sodeoka,
Synlett 2007, 1139–1142; v) T. Suzuki, Y. Hamashima, M. Sodeoka,
Angew. Chem. 2007, 119, 5531–5535; Angew. Chem. Int. Ed. 2007,
4
6, 5435–5439; w) N. Shibata, H. Yasui, S. Nakamura, T. Toru, Syn-
lett 2007, 1153–1157; x) D. S. Reddy, N. Shibata, J. Nagai, S. Naka-
mura, T. Toru, S. Kanemasa, Angew. Chem. 2008, 120, 170–174;
Angew. Chem. Int. Ed. 2008, 47, 164–168; y) D. H. Paull, M. T.
Scerba, E. Alden-Danforth, L. R. Widger, T. Lectka, J. Am. Chem.
Soc. 2008, 130, 17260–17261; z) X. Wang, Q. Lan, S. Shirakawa, K.
Maruoka, Chem. Commun. 2010, 46, 321–323.
[
4] a) E. Differding, R. W. Lang, Tetrahedron Lett. 1988, 29, 6087–6090;
b) T. Umemoto, S. Fukami, G. Tomizawa, K. Harasawa, K. Kawada,
K. Tomita, J. Am. Chem. Soc. 1990, 112, 8563–8575; c) D. S. Brown,
B. A. Marples, P. Smith, L. Malton, Tetrahedron 1995, 51, 3587–
[11] For selected reviews focused on cinchona-alkaloid-derived catalysts,
see: a) T. P. Yoon, E. N. Jacobsen, Science 2003, 299, 1691–1693;
b) S.-K. Tian, Y. Chen, J. Hang, L. Tang, P. McDaid, L. Deng, Acc.
Chem. Res. 2004, 37, 621–631; c) Y.-C. Chen, Synlett 2008, 1919–
1930; d) G. Bartoli, P. Melchiorre, Synlett 2008, 1759–1772; e) T.
Marcelli, H. Hiemstra, Synthesis 2010, 1229–1279; f) L. Jiang, Y.-C.
Chen, Catal. Sci. Technol. 2011, 1, 354–365; g) E. M. O. Yeboah,
S. O. Yeboah, G. S. Singh, Tetrahedron 2011, 67, 1725–1762.
[12] a) Z.-M. Chen, Q.-W. Zhang, Z.-H. Chen, H. Li, Y.-Q. Tu, F.-M.
Zhang, J.-M. Tian, J. Am. Chem. Soc. 2011, 133, 8818–8821; b) H.
Li, F.-M. Zhang, Y.-Q. Tu, Q.-W. Zhang, Z.-M. Chen, Z.-H. Chen, J.
Li, Chem. Sci. 2011, 2, 1839–1841; c) C. H. Mꢁller, M. Wilking, A.
Rꢁhlmann, B. Wibbeling, U. Hennecke, Synlett 2011, 2043–2047.
[13] a) Q.-W. Zhang, C.-A. Fan, H.-J. Zhang, Y.-Q. Tu, Y.-M. Zhao, P.
Gu, Z.-M. Chen, Angew. Chem. 2009, 121, 8724–8726; Angew.
Chem. Int. Ed. 2009, 48, 8572–8574; b) E. Zhang, C.-A. Fan, Y.-Q.
Tu, F.-M. Zhang, Y.-L. Song, J. Am. Chem. Soc. 2009, 131, 14626–
14627; c) M. Wang, Y.-Q. Tu, Acc. Chem. Res. 2011, 44, 1207–1222;
d) Z.-L. Song, C.-A. Fan, Y.-Q. Tu, Chem. Rev. 2011, 111, 7523–
7556.
3
606; d) F. A. Davis, P. Zhou, C. K. Murphy, G. Sundarababu, H. Qi,
W. Han, R. M. Przeslawski, B.-C. Chen, P. Carroll, J. Org. Chem.
998, 63, 2273–2280; e) Y. Takeuchi, Z. Liu, E. Suzuki, N. Shibata,
1
K. L. Kirk, J. Fluorine Chem. 1999, 97, 65–67; f) N. Shibata, T. Ishi-
maru, E. Suzuki, K. L. Kirk, J. Org. Chem. 2003, 68, 2494–2497;
g) L. Zoute, C. Audouard, J.-C. Plaquevent, D. Cahard, Org.
Biomol. Chem. 2003, 1, 1833–1834; h) J.-A. Ma, D. Cahard, J. Fluo-
rine Chem. 2004, 125, 1357–1361; i) D. Enders, M. R. M. Hꢁttl, Syn-
lett 2005, 991–993; j) M. Marigo, D. Fielenbach, A. Braunton, A.
Kjærsgaard, K. A. Jørgensen, Angew. Chem. 2005, 117, 3769–3772;
Angew. Chem. Int. Ed. 2005, 44, 3703–3706; k) D. D. Steiner, N.
Mase, C. F. Barbas III, Angew. Chem. 2005, 117, 3772–3776; Angew.
Chem. Int. Ed. 2005, 44, 3706–3710; l) T. D. Beeson, D. W. C. Mac-
Millan, J. Am. Chem. Soc. 2005, 127, 8826–8828; m) N. Shibata, J.
Kohno, K. Takai, T. Ishimaru, S. Nakamura, T. Toru, S. Kanemasa,
Angew. Chem. 2005, 117, 4276–4279; Angew. Chem. Int. Ed. 2005,
4
4, 4204–4207; n) S. Brandes, B. Niess, M. Bella, A. Prieto, J. Over-
[14] For selected examples of halogenation/semipinacol rearrangement
reactions, see: a) L. A. Paquette, D. R. Owen, R. T. Bibart, C. K.
Seekamp, A. L. Kahane, J. C. Lanter, M. A. Corral, J. Org. Chem.
2001, 66, 2828–2834; b) G. R. Dake, M. D. B. Fenster, P. B. Hurley,
B. O. Patrick, J. Org. Chem. 2004, 69, 5668–5675; c) P. B. Hurley,
G. R. Dake, J. Org. Chem. 2008, 73, 4131–4138; d) S. A. Snyder, Z.-
Y. Tang, R. Gupta, J. Am. Chem. Soc. 2009, 131, 5744–5745; e) T. J.
Snape, Chem. Soc. Rev. 2007, 36, 1823–1842.
gaard, K. A. Jørgensen, Chem. Eur. J. 2006, 12, 6039–6052; o) T.
Ishimaru, N. Shibata, D. S. Reddy, T. Horikawa, S. Nakamura, T.
Toru, Beilstein J. Org. Chem. 2008, 4, 16; p) D. S. Reddy, N. Shibata,
T. Horikawa, S. Suzuki, S. Nakamura, T. Toru, M. Shiro, Chem.
Asian J. 2009, 4, 1411–1415; q) J. Erb, E. Alden-Danforth, N. Kopf,
M. T. Scerba, T. Lectka, J. Org. Chem. 2010, 75, 969–971; r) M. Ka-
watsura, S. Hayashi, Y. Komatsu, S. Hayase, T. Itoh, Chem. Lett.
Chem. Eur. J. 2012, 18, 12950 – 12954
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
12953

Y.-Q. Tu et al.
[
15] We also examined the reaction of 1a with quinine (1.4 equiv) and
Selectfluor (1.4 equiv) in the presence of K CO (0.6 equiv) in
CH CN at RT (the standard reaction conditions used in Ref. [10])
The Cambridge Crystallographic Data Centre via www. ccdc.cam.
ac.uk/data request/cif.
2
3
3
and found that the desired b-fluoroketone was not obtained.
16] CCDC 881661 (4a) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from
[
Received: July 9, 2012
Published online: August 31, 2012
12954
www.chemeurj.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 12950 – 12954