Organocatalytic asymmetric halogenation/semipinacol rearrangement: Highly efficient synthesis of chiral α-oxa-quaternary β-haloketones

Article abstract of DOI:10.1021/ja201794v

A novel asymmetric halogenation/semipinacol rearrangement reaction catalyzed by cinchona alkaloid derivatives was developed. Two types of β-haloketones (X = Br, Cl) were obtained with up to 95% yield and 99% enantiomeric excess. The desired (+) and (-) enantiomers of the β-haloketones were readily obtained.

Full text of DOI:10.1021/ja201794v

COMMUNICATION
pubs.acs.org/JACS
Organocatalytic Asymmetric Halogenation/Semipinacol
Rearrangement: Highly Efficient Synthesis of Chiral r-Oxa-Quaternary
β-Haloketones
Zhi-Min Chen, Qing-Wei Zhang, Zhi-Hua Chen, Hui Li, Yong-Qiang Tu,* Fu-Min Zhang, and Jin-Miao Tian
State Key Laboratory of Applied Organic Chemistry & Department of Chemistry, Lanzhou University, Lanzhou 730000, P.R. China
S Supporting Information
b
Scheme 1. Halogenation/Semipinacol Rearrangement in the
Synthesis of β-Halocarbonyls
ABSTRACT: A novel asymmetric halogenation/semipi-
nacol rearrangement reaction catalyzed by cinchona alkaloid
derivatives was developed. Two types of β-haloketones
(X = Br, Cl) were obtained with up to 95% yield and 99%
enantiomeric excess. The desired (þ) and (ꢀ) enantiomers
of the β-haloketones were readily obtained.
hiral organohalo compounds are a very important class of
Scheme 2. Design for the Catalytic Enantioselective Halo-
genation/Semipinacol Rearrangement
C
synthetic intermediates that are useful for many transforma-
tions in synthetic organic chemistry. There is much interest in
development of synthetic methodologies in this area. Numerous
asymmetric halogenating methods have been developed with
different types of substrates and halogenating reagents.1 Among
them, a number of efforts to develop catalytic asymmetric
halolactonization reactions and some related halocyclizations
have been made,2,3 and some halolactonization processes have
been achieved in high enantioselectivity with organocatalysts
recently.4 Compared with enantioselective halolactonization
reactions, the catalytic asymmetric halogenation/semipinacol
rearrangement reactions are challenging and have attracted less
attention. The halogenation/semipinacol rearrangement of allylic
alcohols is a straightforward and commonly applied strategy for
preparation of β-halocarbonyls, which are versatile intermediates
with a broad range of potential applications in synthesis.5 This
tandem reaction simultaneously forms two adjacent stereocenters,
one of which is quaternary, when starting from simple allylic
alcohols (Scheme 1). Despite these important features, a suitable
catalytic system has not been developed for catalytic asymmetric
halogenation/semipinacol rearrangement reactions.
Recently, cinchona alkaloid derivatives have emerged as
versatile enantioselective catalysts, and their use in a variety of
enantioselective procedures has been widely reported.6 They
have been successfully employed in catalytic enantioselective
halolactonizations.4a,b Inspired by the successful employment of
these catalysts, and combined with our long-standing interest in
semipinacol rearrangement reactions,7 we envisioned synthesis
of chiral β-halocarbonyls 2 by a cinchona alkaloid-catalyzed
halogenation/semipinacol rearrangement of 2-oxa allylic alco-
hols 1 (Scheme 2). Herein, we report preliminary results for the
halogenation/semipinacol rearrangement reaction catalyzed by
cinchona alkaloid derivatives.
available cinchona alkaloids (3aꢀc) were screened with N-
bromosuccinimide (NBS) as the bromine source. Among them,
a catalytic amount of hydroquinidine-2,5-diphenyl-4,6-pyrimidi-
nediyl diether ((DHQD)2PYR) (3c) and 1.1 equiv of NBS in
CCl4 at room temperature gave the best results and produced 2a
in 40% yield and 26% enantiomeric excess (ee) (entries 1ꢀ3).
After 3c was identified as a suitable catalyst, optimization of the
reaction was investigated by varying the halogen source. The
halogen source played a key role in the enantioselectivity of this
reaction. When N-chlorosuccinimide (NCS) was used instead of
NBS the ee decreased, whereas CH3CONHBr increased the
enantioselectivity to 78% ee (entries 4ꢀ7). To further improve
the yield and enantioselectivity, various solvents such as Et2O,
CH2Cl2, and toluene were investigated, wherein toluene was an
effective solvent similar to CCl4 in enantioselectivity (entries
8ꢀ10). By contrast with CCl4, toluene is an inexpensive and
environmentally benign solvent, so further investigation based
on toluene is promising. N-Boc-L-phenylglycine (NBLP) was
investigated as an additive instead of 4-methoxybenzoic acid and
increased the enantioselectivity (entries 11 and 12). Remarkably,
when the reaction temperature was lowered to ꢀ20 °C, the
enantioselectivity was notably improved to 94% ee (entry 13).
The addition of molecular sieves (MS; 5 Å) also greatly improved
the yield to 92% (entry 14). In addition, N-Boc-D-phenylglycine
In our initial study, 2-oxa allylic alcohol 1a was used as a
model substrate, which was prepared according to literature
procedures.7f As indicated in Table 1, some commercially
Received: February 27, 2011
Published: May 06, 2011
r
2011 American Chemical Society
8818
dx.doi.org/10.1021/ja201794v J. Am. Chem. Soc. 2011, 133, 8818–8821
|

Journal of the American Chemical Society
COMMUNICATION
Table 1. Optimization of the Asymmetric Reactiona
Table 2. Asymmetric Bromination Reaction Using Catalyst
(DHQD)2PYRa
entry cat. Xþ source
solvent
additive yield (%)b ee (%)c
1
3a
3b
3c
3c
3c
3c
3c
3c
3c
3c
3c
3c
3c
3c
3c
NBS
CCl4
5
35
20
40
25
35
30
65
ꢀ
8
5
entry
substrate
1a: R1 = R2 = C6H5
1b: R1 = R2 = 4-CH3-C6H4
1c: R1 = R2 = 4-F-C6H4
1d: R1 = R2 = 4-Cl-C6H4
1e: R1 = R2 = 4-CF3-C6H4
1f: R1 = R2 = 4-OMe-C6H4
1g: R1 = R2 = 2-F-C6H4
yield (%)b ee (%)c
2
NBS
CCl4
5
1
92
92
86
78
48
95
61
51
72
91
88
94
98
97
94
91
91
91
99
94
95
95
95
92
3
NBS
CCl4
5
26
11
32
54
78
ꢀ
76
ꢀ
84
88
94
98
97
2
4
NCS
CCl4
5
3
5
DBDMH
CCl4
5
4
6
DCDMH
CCl4
5
5
6d
7
4
4
4
4
4
4
4
4
4
CCl4
5
8
Et2O
5
7
9
toluene
CH2Cl2
CCl4
5
55
ꢀ
8
1h: R1 = R2 = 3-F-C6H4
10
11
12
13d
14d,e
15d,e
5
9
1i: R1 = R2 = 3,5-(CH3)2-C6H3
1j:R1 = R2 = (3,4-methylenedioxy)phenyl
1k: R1 = R2 = 2-naphthyl
1l: R1 = R2 = 2-thienyl
NBLP
NBLP
NBLP
NBLP
NBDP
50
53
74
92
89
10d
11
12d
toluene
toluene
toluene
toluene
a Catalyst (DHQD)2PYR (0.01 mmol) was dissolved in 0.5 mL of
toluene followed by addition of CH3CONHBr (0.11 mmol), NBLP
(0.01 mmol), and 5 Å MS (40 mg). After 10ꢀ30 min, 1aꢀl (0.1 mmol)
in 0.5 mL of toluene was added. b Isolated yield. c Determined by chiral
HPLC analysis. d The reaction proceeded at ꢀ40 °C.
a All reactions were performed with 0.1 mmol of 1a in 1 mL of solvent at
room temperature. b Isolated yield. c Determined by chiral HPLC
analysis. d The reaction was carried out at ꢀ20 °C. 5 Å MS (40 mg)
e
were added.
(NBDP) was also examined as an additive, but with it the yield
and enantioselectivity were slightly reduced (entry 15).
Table 3. Asymmetric Bromination Reaction Using Catalyst
(DHQ)2PYRa
With the optimal conditions established above, the scope of
this reaction was investigated with various 2-oxa allylic alcohols
(1bꢀl). All substrates gave the desired chiral R-oxa-quaternary
β-bromoketone derivatives in moderate to good yields with high
to excellent enantioselectivities (Table 2).8 Compared with the
model substrate 1a, electron-donating groups or electron-with-
drawing groups at the para position of the phenyl moiety
evidently did not change the enantioselectivity but did alter the
yield. Generally, electron-withdrawing aryl substituents gave
lower yields (48ꢀ86%, entries 3ꢀ5), while electron-donating aryl
substituents gave higher yields (95%, entry 6). Meanwhile, the
position of substituents influenced the enantioselectivity slightly
and decreased the yield (entries 7 and 8). Furthermore, multiple
substituents on the phenyl group had little influence on the
enantioselectivity (entries 9 and 10). Notably, 2-naphthyl-substi-
tuted and heteroaromatic-substituted substrates were also amen-
able to the catalytic asymmetric protocol (entries 11 and 12).
The absolute configuration of the product 2l was unambiguously
assigned by X-ray crystallography.9
It is well known that (þ) and (ꢀ) enantiomers commonly
have very different biological activities. Convenient access to
both enantiomers is of great importance in asymmetric catalysis.
To our delight, the reaction of 1a with 10% hydroquinine 2,5-
diphenyl-4,6-pyrimidinediyl diether ((DHQ)2PYR) (3d) and
CH3CONHBr in the presence of NBLP in toluene at ꢀ20 °C
produced 2a0 in 76% yield with 95% ee (Table 3, entry 1). The
reaction was also examined with NBDP, and the enantioselec-
tivity was improved to 96% ee (entry 2). Accordingly, NBDP was
chosen as an alternative additive. Next, the same substrate scope
was explored under the optimized conditions, and the opposite
entry
substrate
1a: R1 = R2 = C6H5
1a: R1 = R2 = C6H5
1b: R1 = R2 = 4-CH3-C6H4
1c: R1 = R2 = 4-F-C6H4
1d: R1 = R2 = 4-Cl-C6H4
1e: R1 = R2 = 4-CF3-C6H4
1f: R1 = R2 = 4-OMe-C6H4
1g: R1 = R2 = 2-F-C6H4
yield (%)b ee (%)c
1d
2
76
74
86
72
63
31
91
40
43
78
69
66
86
95
96
95
82
82
87
81
98
88
96
89
97
93
3
4
5e
6e
7f
8
9e
10
11f
12
13
1h: R1 = R2 = 3-F-C6H4
1i: R1 = R2 = 3,5-(CH3)2-C6H3
1j: R1 = R2 = (3,4-methylenedioxy)phenyl
1k: R1 = R2 = 2-naphthyl
1l: R1 = R2 = 2-thienyl
a Catalyst (DHQ)2PYR (0.01 mmol) was dissolved in 0.5 mL of toluene,
followed by addition of CH3CONHBr (0.11 mmol), NBDP (0.01
mmol), and 5 Å MS (40 mg). After 10ꢀ30 min, 1aꢀl (0.1 mmol) in
c
0.5 mL of toluene was added. b Isolated yield. Determined by chiral
HPLC analysis. d The additive was NBLP. e The reaction proceeded at
ꢀ10 °C. f The reaction proceeded at ꢀ30 °C.
8819
dx.doi.org/10.1021/ja201794v |J. Am. Chem. Soc. 2011, 133, 8818–8821

Journal of the American Chemical Society
COMMUNICATION
Table 4. Asymmetric Chlorination Reactiona
Scheme 3. Asymmetric Bromination Reaction on a 1 mmol
Scale
entry
substrate
cat.
product
yield (%)b
ee (%)c
1
1a
1a
1b
1b
1c
1c
1g
1g
1k
1k
3c
3d
3c
3d
3c
3d
3c
3d
3c
3d
6a
67
49
69
42
76
40
54
41
66
48
96d
94
94
74
91
76
99
95
86
86
excellent ee. Further studies are underway to determine the
mechanism and investigate applications for related reactions, and
those will be reported in due course.
2
6a0
6b
6b0
6c
6c0
6g
6g0
6k
6k0
3
4e
’ ASSOCIATED CONTENT
5
6e
7
8e
9f
10e,f
S
Supporting Information. Experimental details, com-
b
pound characterization, and X-ray crystallographic data (CIF)
for 2l and 6a. This material is available free of charge via the
Internet at http://pubs.acs.org.
a Catalyst 3c or 3d (0.01 mmol) was dissolved in 0.5 mL of toluene,
followed by addition of DCDMH (0.11 mmol), NBLP (0.01 mmol),
and 5 Å MS (40 mg). After 10ꢀ30 min, 1aꢀc, 1g, and 1k (0.1 mmol) in
HPLC analysis. d Absolute configuration was determined by X-ray
crystallography of 6a (see Supporting Information). e DCDPH was
added instead of DCDMH. f The reaction proceeded at ꢀ70 °C.
’ AUTHOR INFORMATION
Corresponding Author
tuyq@lzu.edu.cn
c
0.5 mL of toluene were added. b Isolated yield. Determined by chiral
’ ACKNOWLEDGMENT
This work was supported by the NSFC (Nos. 20921120404,
20732002, and 20972059), “973” program of 2010CB833200,
“111” program of MOE, and the fundamental research funds for
the central universities (lzujbky-2010-k09, lzujbky-2009-76,
lzujbky-2009-158).
enantiomers of the products (2a0ꢀl0) were obtained with
moderate to excellent ee in moderate to good yields. By contrast
to the products 2aꢀl, the products 2a0ꢀl0 were obtained in
relatively low yields (31ꢀ91%). In some cases, the electronic
nature of the substituents on the phenyl group appeared to
negatively affect the ee (entries 4ꢀ7).
’ REFERENCES
It is noteworthy that β-chloroketones also have important
synthetic utility and bioactivity.10 However, there are very few
reports on enantioselective synthesis of β-chloroketones.11 Con-
sequently, we began investigating development of a catalytic
asymmetric synthesis for chiral β-chloroketones. The good results
for asymmetric bromination indicated that chiral β-chloroketone
synthesis might be achieved with an appropriate chlorine source.
NCS, 1,3-dichloro-5,5-dimethylhydantoin (DCDMH),12 and 1,
3-dichloro-5,5-diphenylhydantoin (DCDPH)12 were screened as
chlorinesourcesinthe model reaction atꢀ50 °C. WhenDCDMH
or DCDPH was used as the chlorine source, the corresponding
products were produced with moderate to high enantioselectiv-
ities for both diastereomers and moderate yields (Table 4). It
should be noted that we also examined the effect of NBDP as an
additive in our initial studies and found that it decreased the yield
and enantioselectivity.13
To evaluate the synthetic utility of the catalyst system, a 1
mmol scale rearrangement of substrate 1a was performed under
the standard reaction conditions. As shown in Scheme 3, the
desired product 2a was obtained in 83% yield with 96% ee.
In conclusion, we have developed a novel asymmetric
halogenation/semipinacol rearrangement reaction catalyzed by
cinchona alkaloid derivatives. This reaction is valuable and
versatile since two adjacent stereocenters, one of which is the
chiral oxa-quaternary carbon, were constructed effectively and
two types of β-haloketo compounds (X = Br, Cl) were readily
obtained. Moreover, the desired (þ) and (ꢀ) enantiomers of the
products were obtained with moderate to good yields and high to
(1) Recent reviews focused on the asymmetric halogenation: (a) Ma,
J.-A.; Cahard, D. Chem. Rev. 2004, 104, 6119. (b) Ibrahim, H.; Togni, A.
Chem. Commun. 2004, 1147. (c) French, A. N.; Bissmire, S.; Wirth, T.
Chem. Soc. Rev. 2004, 33, 354. (d) Oestreich, M. Angew. Chem., Int. Ed.
2005, 44, 2324. (e) France, S.; Weatherwax, A.; Lectka, T. Eur. J. Org.
Chem. 2005, 475. (f) Marigo, M.; Jørgensen, K. A. Chem. Commun.
2006, 2001. (g) Shibata, N.; Ishimaru, T.; Nakamura, S.; Toru, T.
J. Fluorine Chem. 2007, 128, 469. (h) Brunet, V. A.; O’Hagan, D. Angew.
Chem., Int. Ed. 2008, 47, 1179. (i) Ma, J.-A.; Cahard, D. Chem. Rev. 2008,
108, PR1. (j) Ueda, M.; Kano, T.; Maruoka, K. Org. Biomol. Chem. 2009,
7, 2005. (k) Shibatomi, K. Synthesis 2010, 2679. (l) Chen, G.; Ma, S.
Angew. Chem., Int. Ed. 2010, 49, 8306.
(2) Selected examples of asymmetric halolactonization reactions:
(a) Grossman, R. B.; Trupp, R. J. Can. J. Chem. 1998, 76, 1233. (b) Cui,
X. L.; Brown, R. S. J. Org. Chem. 2000, 65, 5653. (c) Haas, J.; Piguel, S.;
Wirth, T. Org. Lett. 2002, 4, 297. (d) Wang, M.; Gao, L. X.; Mai, W. P.;
Xia, A. X.; Wang, F.; Zhang, S. B. J. Org. Chem. 2004, 69, 2874. (e) Wang,
M.; Gao, L. X.; Yue, W.; Mai, W. P. Synth. Commun. 2004, 34, 1023.
(f) Haas, J.; Bissmire, S.; Wirth, T. Chem.—Eur. J. 2005, 11, 5777.
(g) Garnier, J. M.; Robin, S.; Rousseau, G. Eur. J. Org. Chem. 2007, 3281.
(h) Ning, Z. L.; Jin, R. H.; Ding, J. Y.; Gao, L. X. Synlett 2009, 2291.
(3) Selected examples of asymmetric halocyclization reactions:
(a) Kitagawa, O.; Hanano, T.; Tanabe, K.; Shiro, M.; Taguchi, T. J.
Chem. Soc., Chem. Commun. 1992, 1005. (b) Kitagawa, O.; Taguchi, T.
Synlett 1998, 1191. (c) Kang, S. H.; Lee, S. B.; Park, C. M. J. Am. Chem.
Soc. 2003, 125, 15748. (d) Sakakura, A.; Ukai, A.; Ishihara, K. Nature
2007, 445, 900. (e) Kwon, H. Y.; Park, C. M.; Lee, S. B.; Youn, J. H.;
Kang, S. H. Chem.—Eur. J. 2008, 14, 1023.
(4) (a) Whitehead, D. C.; Yousefi, R.; Jaganathan, A.; Borhan, B.
J. Am. Chem. Soc. 2010, 132, 3298. (b) Zhang, W.; Zheng, S.; Liu, N.;
8820
dx.doi.org/10.1021/ja201794v |J. Am. Chem. Soc. 2011, 133, 8818–8821

Journal of the American Chemical Society
COMMUNICATION
Werness, J. B.; Guzei, I. A.; Tang, W. J. Am. Chem. Soc. 2010, 132, 3664.
(c) Veitch, G. E.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2010, 49, 7332.
(d) Murai, K.; Matsushita, T.; Nakamura, A.; Fukushima, S.; Shimura,
M.; Fujioka, H. Angew. Chem., Int. Ed. 2010, 49, 9174. (e) Zhou, L.; Tan,
C. T.; Jiang, X.; Chen, F.; Yeung, Y.-Y. J. Am. Chem. Soc. 2010,
132, 15474. (f) Yousefi, R.; Whitehead, D. C.; Mueller, J. M.; Staples,
R. J.; Borhan, B. Org. Lett. 2011, 13, 608.
(5) (a) Koppenhoefer, B.; Lohmiller, K.; Schurig, F. V. In Encyclo-
pedia of Reagents for Organic Synthesis; Paquette, L. A., Ed.; John Wiley
and Sons: Chichester, 1995; Vol. 6, pp 4331. (b) Maroto, B. L.; Cerero,
S; de la, M.; Martínez, A. G.; Fraile, A. G.; Vilar, E. T. Tetrahedron:
Asymmetry 2000, 11, 3059. (c) Martínez, A. G.; Vilar, E. T.; Fraile, A. G.;
Cerero, S; de la, M.; Maroto, B. L. Tetrahedron Lett. 2001, 42, 6539. (d)
Paquette, L. A.; Owen, D. R.; Bibart, R. T.; Seekamp, C. K.; Kahane,
A. L.; Lanter, J. C.; Corral, M. A. J. Org. Chem. 2001, 66, 2828. (e)
Hurley, P. B.; Dake, G. R. Synlett 2003, 2131. (f) Dake, G. R.; Fenster,
M. D. B.; Hurley, P. B.; Patrick, B. O. J. Org. Chem. 2004, 69, 5668. (g)
Fan, C.-A.; Tu, Y.-Q.; Song, Z.-L.; Zhang, E.; Shi, L.; Wang, M.; Wang,
B.-M.; Zhang, S.-Y. Org. Lett. 2004, 6, 4691. (h) Hu, X.-D.; Tu, Y.-Q.;
Zhang, E.; Gao, S.-H.; Wang, S.-H.; Wang, A.-X.; Fan, C.-A.; Wang, M.
Org. Lett. 2006, 8, 1823. (i) Snape, T. Chem. Soc. Rev. 2007, 36, 1823. (j)
Hurley, P. B.; Dake, G. R. J. Org. Chem. 2008, 73, 4131.
(6) Selected applications of cinchona alkaloids in the asymmetric
reactions: (a) Chen, Y.; Tian, S.-K.; Deng, L. J. Am. Chem. Soc. 2000,
122, 9542. (b) Tian, S.-K.; Chen, Y.; Hang, J.; Tang, L.; McDaid, P.;
Deng, L. Acc. Chem. Res. 2004, 37, 621. (c) Chen, W.; Du, W.; Duan,
Y.-Z.;Wu, Y.;Yang, S.-Y.;Chen, Y.-C. Angew. Chem., Int. Ed. 2007, 46, 7667.
(d) Cinchona Alkaloids in Synthesis & Catalysis: Ligands, Immobilization and
Organocatalysis; Song, C. E., Ed.; Wiley-VCH: Weinheim, Germany, 2009.
(e) Wu, L.-Y.; Bencivenni, G.; Mancinelli, M.; Mazzanti, A.; Bartoli, G.;
Melchiorre, P. Angew. Chem., Int. Ed. 2009, 48, 7196. (f) Galzerano, P.;
Pesciaioli, F.; Mazzanti, A.; Bartoli, G.; Melchiorre, P. Angew. Chem., Int. Ed.
2009, 48, 7892. (g) Paix~ao, M. W.; Holub, N.; Vila, C.; Nielsen, M.;
Jørgensen, K. A. Angew. Chem., Int. Ed. 2009, 48, 7338.
(7) (a) Tu, Y.-Q.; Sun, L.-D.; Wang, P.-Z. J. Org. Chem. 1999,
64, 629. (b) Wang, B.-M.; Song, Z.-L.; Fan, C.-A.; Tu, Y.-Q.; Chen,
W.-M. Synlett 2003, 1497. (c) Hu, X.-D.; Fan, C.-A.; Zhang, F.-M.; Tu,
Y.-Q. Angew. Chem., Int. Ed. 2004, 43, 1702. (d) Wang, M.; Wang, B.-M.;
Shi, L.; Tu, Y.-Q.; Fan, C.-A.; Wang, S.-H.; Hu, X.-D.; Zhang, S.-Y. Chem.
Commun. 2005, 5580. (e) Gu, P.; Zhao, Y.-M.; Tu, Y.-Q.; Ma, Y.-F.;
Zhang, F.-M. Org. Lett. 2006, 8, 5271. (f) Zhang, Q.-W.; Fan, C.-A.;
Zhang, H.-J.; Tu, Y.-Q.; Zhao, Y.-M.; Gu, P.; Chen, Z.-M. Angew. Chem.,
Int. Ed. 2009, 48, 8572. (g) Zhang, E.; Fan, C.-A.; Tu, Y.-Q.; Zhang,
F.-M.; Song, Y.-L. J. Am. Chem. Soc. 2009, 131, 14626.
(8) We also examined CCl4 as the solvent in our reaction system and
found that two types of β-haloketo compounds (X = Br, Cl) were also
obtained with moderate to good yields and high to excellent ee. For
details, see Supporting Information.
(9) For details, see Supporting Information.
(10) (a) Zoretic, P. A.; Bendiksen, B.; Branchaud, B. J. Org. Chem.
1976, 41, 3767. (b) Miller, J. A.; Ullah, G. M.; Welsh, G. M.; Mallon, P.
Tetrahedron Lett. 2001, 42, 2729.
(11) Snyder, S. A.; Tang, Z.-Y.; Gupta, R. J. Am. Chem. Soc. 2009,
131, 5744.
(12) Whitehead, D. C.; Staples, R. J.; Borhan, B. Tetrahedron Lett.
2009, 50, 656.
(13) The reaction of 1a with 3c (0.1 equiv) and DCDMH (1.1
equiv) in the presence of NBDP (0.1 equiv) in toluene at ꢀ50 °C
produced 6a in 54% yield with 95% ee. Likewise, the reaction of 1a with
3d (0.1 equiv) and DCDMH (1.1 equiv) in the presence of NBDP
(0.1 equiv) in toluene at ꢀ50 °C produced 6a0 in 45% yield with 93% ee.
’ NOTE ADDED AFTER ASAP PUBLICATION
Two references were omitted from the version of this Commu-
nication published ASAP May 11, 2011. New refs 6a,b were
added in the version posted May 20, 2011.
8821
dx.doi.org/10.1021/ja201794v |J. Am. Chem. Soc. 2011, 133, 8818–8821