report has yet been published on the direct asymmetric variant
of these easily prepared but useful γ-substituted butenolides.6
Recently, the allylic alkylation with Morita-Baylis-Hillman
(MBH) adducts by the catalysis of metal-free Lewis basic
tertiary amines or phosphines has emerged as a powerful
strategy to deliver multifunctional compounds.7,8 Krische9a
reported the first phosphine-catalyzed allylic alkylation of
2-silyloxyfuran with MBH acetates in excellent regio- and
diastereoselectivities. Later Shi9b developed the first asym-
metric variant to afford γ-substituted butenolides by employ-
ing newly designed chiral bifunctional phosphine catalysts.
However, limitation of substrate to preformed 2-silyloxyfuran
without any substitution incapacitated access to enantioen-
riched γ,γ-disubstituted butenolides. We envisioned that, as
outlined in Scheme 1, the direct tertiary amine-catalyzed
2a in the presence of DABCO (20 mol %) in DCE at ambient
temperature. To our delight, the reaction proceeded very
smoothly, and the regioselective γ,γ-disubstituted butenolide
3a was obtained with excellent diastereoselectivity (>95:5)12
in 88% yield after 1 h, although some unidentified byproduct
was also observed (Table 1, entry 1). We then examined the
Table 1. Screening Studies of Direct Asymmetric Allylic
Alkylation of ꢀ,γ-Butenolides 1a with MBH Carbonate 2aa
entry
catalystb
DABCO
(DHQD)2AQN
(DHQD)2PHAL DCE
(DHQD)2PYR
(DHQ)2AQN
(DHQ)2PYR
(DHQD)2PYR
(DHQD)2PYR
(DHQD)2PYR
(DHQD)2PYR
(DHQD)2PYR
(DHQ)2PYR
solvent t (h) yieldc (%) eed (%)
1e
2
3
4
5
6
7
8
DCE
DCE
1
19
24
18
24
25
32
22
47
54
10
19
88
61
66
90
35
65
60
78
62
54
82
45
Scheme 1
.
Proposed Direct Allylic Alkylation of γ-Substituted
Butenolides with MBH Carbonates
83
81
DCE
85
DCE
DCE
-10
-35
91
92
93
92
92
-46
toluene
PhCF3
PhCF3
PhCF3
PhCF3
PhCF3
9f
10g
11h
12h
a Unless otherwise noted, reactions were performed with 0.1 mmol of
1a, 0.2 mmol of 2a, and 10 mol % of catalyst in 1.0 mL of solvent at 50
°C. b DABCO: 1,4-diazabicyclo[2.2.2]octane. (DHQD)2AQN: hydroquini-
dine (anthraxquinone-1,4-diyl) diether. (DHQD)2PHAL: hydroquinidine 1,4-
phthalazinediyl diether. (DHQD)2PYR: hydroquinidine-2,5-diphenyl-4,6-
pyrimidinediyl diether. (DHQ)2AQN: hydroquinineanthraxquinone-1,4-diyl
diether. (DHQ)2PYR: hydroquinine-2,5-diphenyl-4,6-pyrimidinediyl diether.
c Isolated yield of pure 3a (dr >95:5).12 d Determined by chiral HPLC
analysis. e At rt, with 20 mol % of catalyst. f At 35 °C. g 10 mol % of
S-BINOL was added. h In 0.5 mL of solvent.
asymmetric γ-allylic alkylation of γ-substituted butenolides
would be realized via deprotonation by an in situ generated
tert-butoxy anion and subsequent vinylogous addition reac-
tion. We wondered whether the chemo-, regio-, and stereo-
selectivities could be well accomplished simultaneously,
although the rather challenging construction of adjacent
quaternary and tertiary chiral centers must be fulfilled.10,11
We began our investigation with the reaction of ꢀ,γ-
butenolide 1a bearing a γ-aryl substitution with MBH carbonate
asymmetric catalytic ability of some modified cinchona alka-
loids at higher temperature (entries 2-6).13 The screening
studies revealed that (DHQD)2PYR was the best choice in terms
(9) (a) Cho, C.-W.; Krische, M. J. Angew. Chem., Int. Ed. 2004, 43,
6689. (b) Jiang, Y.-Q.; Shi, Y.-L.; Shi, M. J. Am. Chem. Soc. 2008, 130,
7202.
(10) For reviews on the construction of a quaternary carbon center, see:
(a) Christoffers, J.; Baro, A. AdV. Synth. Catal. 2005, 347, 1473. (b) Cozzi,
P. G.; Hilgraf, R.; Zimmermann, N. Eur. J. Org. Chem. 2007, 5969. (c)
Bella, M.; Gasperi, T. Synthesis 2009, 1583.
(6) For catalytic asymmetric synthesis of γ,γ-disubstituted butenolides,
see: (a) Brown, S. P.; Goodwin, N. C.; MacMillan, D. W. C. J. Am. Chem.
Soc. 2003, 125, 1192. (b) Shaw, S. A.; Aleman, P.; Christy, J.; Kampf,
J. W.; Va, P.; Vedejs, E. J. Am. Chem. Soc. 2006, 128, 925.
(11) For selected examples of the construction of adjacent quaternary
and tertiary chiral centers, see: (a) Austin, J. F.; Kim, S.-G.; Sinz, C. J.;
Xiao, W.-J.; MacMillan, D. W. C. Proc. Natl. Acad. Sci. U.S.A. 2004, 101,
5482. (b) Li, H.; Wang, Y.; Tang, L.; Wu, F.; Liu, X.; Guo, C.; Foxman,
B. M.; Deng, L. Angew. Chem., Int. Ed. 2005, 44, 105. (c) Trost, B. M.;
Zhang, Y. J. Am. Chem. Soc. 2007, 129, 14548. (d) Wilt, J. C.; Pink, M.;
Johnston, J. N. Chem. Commun. 2008, 4177. (e) Bui, T.; Syed, S.; Barbas,
C. F., III J. Am. Chem. Soc. 2009, 131, 8758. (f) Kato, Y.; Furutachi, M.;
Chen, Z.; Mitsunuma, H.; Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc.
2009, 131, 9168.
(7) (a) Kim, J. N.; Lee, H. J.; Gong, J. H. Tetrahedron Lett. 2002, 43,
9141. (b) Cho, C.-W.; Kong, J.-R.; Krische, M. J. Org. Lett. 2004, 6, 1337.
(c) Du, Y.; Han, X; Lu, X. Tetrahedron Lett. 2004, 45, 4967. (d) Zhang,
T.-Z.; Dai, L.-X.; Hou, X.-L. Tetrahedron: Asymmetry 2007, 18, 1990. (e)
van Steenis, D. J. V. C.; Marcelli, T.; Lutz, M.; Spek, A. L.; van Maarseveen,
J. H.; Hiemstra, H. AdV. Synth. Catal. 2007, 349, 281. (f) Park, H.; Cho,
C.-W.; Krische, M. J. J. Org. Chem. 2006, 71, 7892. (g) Ma, G.-N.; Cao,
S.-H.; Shi, M. Tetrahedron: Asymmetry 2009, 20, 1086
.
(8) For studies from this group, see: (a) Cui, H.-L.; Peng, J.; Feng, X.;
Du, W.; Jiang, K.; Chen, Y.-C. Chem.sEur. J. 2009, 15, 1574. (b) Jiang,
K.; Peng, J.; Cui, H.-L.; Chen, Y.-C. Chem. Commun. 2009, 3955. (c) Cui,
H.-L.; Feng, X.; Peng, J.; Jiang, K.; Chen, Y.-C. Angew. Chem., Int. Ed.
2009, 48, 5737. (d) Feng, X.; Yuan, Y.-Q.; Cui, H.-L.; Jiang, K.; Chen,
Y.-C. Org. Biomol. Chem. 2009, 7, 3660. (e) Zhang, S.-J.; Cui, H.-L.; Jiang,
(12) The diastereomeric ratio of >95:5 indicates that the minor isomer
could not be detected by 1H NMR analysis. Excellent diastereoselectivities
(generally >95:5) were reported in the similar reaction of 2-silyloxyfuran
by Krische and Shi; see ref 9.
(13) For reviews, see: (a) Tian, S.-K.; Chen, Y.; Hang, J.; Tang, L.;
McDaid, P.; Deng, L. Acc. Chem. Res. 2004, 37, 621. (b) Gaunt, M. J.;
Johansson, C. C. C. Chem. ReV. 2007, 107, 5596.
K.; Li, R.; Ding, Z.-Y.; Chen, Y.-C. Eur. J. Org. Chem. 2009, 5804
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