Highly enantioselective [3+2] annulation of cyclic enol silyl ethers with donor-acceptor cyclopropanes: Accessing 3a-hydroxy [n.3.0]carbobicycles

Article abstract of DOI:10.1002/anie.201300032

A new fuse: The title reaction was realized using a new bisoxazoline (BOX)/Cu^II catalyst. This reaction works well with cyclic enol silyl ethers of different sizes, and can be extended to dienol and benzene-fused substrates, thus providing an effective and general access to a range of 3a-hydroxy [n.3.0]carbobicycles which are found as a core structure in many natural products. TBDPS=tert-butyldiphenylsilyl.

Full text of DOI:10.1002/anie.201300032

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Angewandte
Communications
DOI: 10.1002/anie.201300032
Asymmetric Catalysis
Highly Enantioselective [3+2] Annulation of Cyclic Enol Silyl Ethers
with Donor–Acceptor Cyclopropanes: Accessing 3a-Hydroxy
[n.3.0]Carbobicycles**
Hao Xu, Jian-Ping Qu, Saihu Liao, Hu Xiong, and Yong Tang*
[n.3.0]Carbobicycles containing a tertiary alcohol moiety
located at the ring junction are found as a key structure in
a large number of biologically active and naturally occurring
molecules such as botrydials, africanols, palustrols, lucinones,
furoscrobiculins, etc. (Figure 1).[1] In the past decades, con-
siderable effort[2–7] has been focused on the synthesis of these
[n.3.0]bicycles, and many methods have been documented,
silyl ethers with donor–acceptor (D–A) cyclopropanes using
copper(II)/bisoxazoline (BOX) catalysts.[6] However, initial
attempts to employ chiral Ph-PYBOX and Ph-DBFOX for
the asymmetric version gave very poor results.[8,9] To our
delight, the annulation reaction can finally be accomplished
with high diastereo- and enantioselectivity by using modified
BOX ligands, thus providing a new and facile access to a series
of optically active 3a-hydroxy [n.3.0]carbobicycles. Herein we
report the preliminary results.
In view of the prevalence of [5.3.0]bicyclic skeletons in
natural products,[1b,c,e–h] we first commenced our study with
the screening of BOX ligands using the cycloheptanone-
derived enol silyl ether 1 and PMP-substituted cyclopropane 2
(Table 1). Cu(ClO4)2 was employed as the copper(II) source
and dichloromethane as the solvent.[6] A screening of several
Table 1: Reaction optimization.[a]
Figure 1. 3a-Hydroxy [n.3.0]carbobicycles in natural products.
such as nBu3SnC- or SmI2-initiated radical cyclization,[2] ring-
closing metathesis,[3] and [n + 2] annulations[4–6] based on
cyclic enol ethers. So far, however, very few direct and
catalytic asymmetric versions have been developed.[3a,4h,i] As
the [3+2] annulation[5] of cyclic enol ethers with cyclo-
propanes can efficiently establish the bicyclic skeleton, the
tertiary alcohol unit, and at least two contiguous chiral centers
in one step, it provides an appealing and concise approach to
synthesize the 3a-hydroxy [n.3.0]carbobicyclic structure.
Unfortunately, this efficient cycloaddition method often
results in low diastereoselectivity and the formation of the
ring-opened side products.[5] Recently, we showed a highly
efficient and diastereoselective annulation reaction of enol
Entry
1
2
L
t [h]
Conv. [%][b]
d.r.[b]
ee [%][c]
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
2a
2a
2a
2a
2a
2a
2a
2b
2a
2a
L1
L2
L3
L4
L5
L6
L7
L7
L7
L7
24
24
24
24
24
24
11
42
19
10
88
92
>99
>99
>99
>99
>99(85)
>99
88(0)
>99(27)
80:20
85:15
86:14
84:16
85:15
82:18
87:13
80:20
–
76
93
95
90
96
97
97
88
[*] H. Xu,[+] J. P. Qu,[+] Dr. S. Liao, H. Xiong, Prof. Dr. Y. Tang
State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences
345 Lingling Lu, Shanghai 200032 (P.R. China)
tangy@ sioc.ac.cn
(94)[d]
90(96)[d]
10
68:32
[a] Reaction conditions: [Cu(ClO4)2·6H2O] (0.02 mmol), L (0.022 mmol),
1 (0.30 mmol), and 2 (0.20 mmol) in 2.0 mL of CH2Cl2. [b] Conversion
and d.r. values (cis/trans) were determined by 1H NMR spectroscopy.
Value within the parentheses is the yield of the isolated product.
[c] Measured by HPLC using a chiral stationary phase. The ee values are
those of the cis products. [d] The ee values within the parentheses are of
the major isomer (d.r. >20:1) of product 4. PMP=para-methoxyphenyl,
TBDPS=tert-butyldiphenylysilyl, TBS=tert-butyldimethylsilyl, TIPS
=triisopropylsilyl.
[+] These authors contributed equally to this work.
[**] We are grateful for the financial support from the National Natural
Sciences Foundation of China (20932008 and 21121062), the Major
State Basic Research Development Program (Grant No.
2009CB825300), and the Chinese Academy of Sciences.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201300032.
4004
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Table 2: Reaction scope.[a]
bisoxazoline ligands unveiled that iPr-BOX gave the best
enantioselectivity (entry 2),[8] and encouraged us to further
elaborate this framework. To our delight, the sidearm
strategy[10,11] of introducing a pendant group at the bridging
carbon atom of the bisoxazoline ligand proved to be quite
effective in this reaction, and the enantioselectivity of the
reaction was gradually improved to 97% ee by increasing the
steric hindrance at the para position of the aryl sidearm
groups (entries 3–7). It is worth noting that the racemic D–A
cyclopropanes 2a and 2b were used in this reaction, thus
suggesting that the current reaction proceeds with a dynamic
kinetic resolution[9b–d] of the cyclopropanes. Reaction accel-
eration was consistently observed with the sidearm-modified
ligands (entries 3–7 versus entries 1 and 2). In contrast,
alteration of the ester group of 2 indicated that a large ester
group is also important to the enantioselectivity with 2-
adamantyl (Ad) being the best (entry 7 versus 8).[12] It is
noteworthy that the TBDPS protecting group proved to be
crucial to suppress the formation of the ring-opened product 4
and ensure a high yield of the desired [3+2] product (entries 9
and 10). For example, in the reactions of the TBDPS enol
ether 1a, only a trace or a small (< 10%) amount of the ring-
opened product can be detected by proton NMR spectrosco-
py, which is in contrast to reaction of the TIPS-protected enol
ether 1b which exclusively produced the ring-opened product
(entry 9). The formation of 4 may result from the hydrolysis of
the carboxonium intermediate before the ring closure or the
abstraction of its a proton followed by desilylation.[5,6] In
addition, other metal salts such as Cu(SbF6)2, Cu(OTf)2,
CuBr2, Ni(ClO4)2, and Co(ClO4)2 were also examined. Only
Cu(SbF6)2 and Cu(OTf)2 showed a good activity, but resulted
in slightly lower enantioselectivities.[8]
Entry
1
R2
P
Yield [%]
(d.r.)[b]
ee
[%][c]
1
2
4-MeOC6H4 (2a)
2-thiophenyl (2c)
(3,4,5-MeO)3C6H2 (2d) 3ad 78 (91:9)
3aa 85 (87:13)
3ac 62 (87:13)
97
93
99
92
3[d]
4
=
CH CHPh (2e)
3ae 74 (80:20)
5
4-MeOC6H4 (2a)
4-MeOC6H4 (2a)
4-MeOC6H4 (2a)
3da 94 (81:19)
91
92
6[e]
3ea 70 (85:15)
7
3 fa 61 (>99:1) 95
8
9
4-MeOC6H4(2a)
2-thiophenyl (2c)
3ga 87 (>99:1) 93
3gc 83 (>99:1) 93
10
(3,4,5-MeO)3C6H2 (2d) 3gd 81 (>99:1) 97
11[f,14]
12[g]
CH CHPh (2e)
2-furyl (2 f)
3ge 45 (>99:1) 95
3gf 68 (>99:1) 92
=
13[e,14]
4-MeOC6H4 (2a)
3ha 45 (>95:5) 98[h]
Having the optimized reaction conditions, we moved to
the investigation of the reaction scope. As shown in Table 2,
apart from a PMP-substituted D–A cyclopropane, 2-thio-
phenyl- (2c), 3,4,5-trimethoxyphenyl- (TMP, 2d), and
alkenyl-substituted (2e) cyclopropanes also reacted well
with 1a, thus giving the desired fused cyclic products in
good to excellent enantiomeric excesses (entries 1–4). The
reaction of the TMP-substituted cyclopropane was slower,
and could probably be ascribed to the steric hindrance of the
TMP group or the competing bidentate coordination of the
methoxy groups to the copper (entry 3). Notably, both
conjugate and isolated dienol-ether-type substrates (1d and
1e) also react smoothly under the standard reaction con-
ditions, thus affording carbon–carbon double-bond-contain-
ing [5.3.0]bicyclic products, with the potential for additional
transformation of this functionality (entries 5 and 6). To our
great pleasure, the current reaction works quite well with six-
and five-membered substrates (entries 7–13). Thus, a range of
[n.3.0] (n = 3–5) 3a-hydroxy bicycles in high enantiomeric
purity are accessible by this reaction. Remarkably, in the
reactions with five- and six-membered enol silyl ethers,
perfect diastereoselectivities (> 99:1) were consistently
observed (entries 7–12). In fact, in these cases only one
diastereoisomer was detected by 1H NMR analysis of the
crude reaction mixture. In addition, the ß-disubstituted enol
silyl ether 1h is also a suitable substrate with high enantio-
selectivity, and notably the corresponding product (3ha)
[a] Reaction conditions: [Cu(ClO4)2·6H2O] (0.02 mmol), L7
(0.022 mmol), 1 (0.30 mmol), and 2 (0.20 mmol) in 2.0 mL of CH2Cl2 at
308C with 4 ꢀ M.S. and N2. [b] Yield of the isolated product. A trace
amount of ring-opened product 4 was observed. The d.r. values (cis/
1
trans) were determined by H NMR spectroscopy. [c] Values for the cis
products as determined by HPLC using a chiral stationary phase.
[d] Using 3 equiv of 1a. [e] Cu(SbF6)2. [f] Cu(OTf)2, Ref. [14]. [g] Cu-
(OTf)2, 08C, in 1,1,2,2-tertrachloroethane. [h] When Cu(SbF6)2 was used,
the yield was 70% with 91% ee. Ad=2-adamantyl, M.S.=molecular
sieves, Tf=trifluoromethanesulfonyl.
contains three contiguous quaternary centers, two of which
are at the ring juncture (entry 13). The configurations of the
products 3aa, 3da, and 3gc were determined by X-ray crystal
structure analysis,[13] and the configurations of other products
were assigned by analogy.
The success with monocyclic enol silyl ethers encouraged
us to extend the current method to benzocyclic enol silyl
ethers, which can deliver the benzene-fused cyclic products.
As shown in Scheme 1, the reaction works extraordinarily
well with these benzene-fused substrates, such as 3,4-dihy-
dronaphthalen-1-one- and 1-indanone-derived silyl enol
ethers (5a–f), and different substitution patterns such as 6-
bromo, 6-fluoro, 7-methyl, and 5-methyl substituents are
tolerated under the standard reaction conditions. In all cases
high yield (80–98%) and complete diastereoselectivity
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Scheme 3. Transformations of the annulation products. DIBAL-H=di-
isobutylaluminum hydride.
seven-membered cyclic-ketone-derived enol silyl ethers, and
can be further extended to a,b-unsaturated- and benzocyclic-
ketone-derived substrates. To our knowledge, these reactions
represent the first examples of catalytic enantioselective
[3+2] annulation reactions of enol silyl ethers with cyclo-
propanes. Further exploration and application of the current
reaction to natural product synthesis is ongoing in our
laboratory.
Scheme 1. Extension to the syntheses of benzocycles.
(> 99:1) were obtained. The sterically demanding 4,7-
dimethyl-substituted enol silyl ether 5 f also reacted well
under the current reaction conditions, thus giving the desired
cycloaddition product 6 fa in 91% yield and 93% ee.
For less reactive cyclopropanes, it is worth mentioning
that the present reaction proceeds in a kinetic resolution
fashion, though normally the reaction is slower. As exempli- Experimental Section
Typical procedure (3aa as an example):
A mixture of [Cu-
fied in Scheme 2, a high selectivity factor (S = 152) was
(ClO4)2·6H2O] (0.02 mmol) and the ligand (L7, 0.022 mmol) in
dichloromeethane (1.0 mL), with activated 4 ꢀ M.S., was stirred at
room temperature for 2 h under N2. Then the mixture was then
warmed to 308C for 10 min, and the cyclopropane 2a (0.20 mmol) was
added. The enol silyl ether 1a (0.30 mmol) in dichloromethane
(1.0 mL) was then added. The resulting solution was stirred until the
cyclopropane was completely consumed. The reaction mixture was
then passed through a short silica gel column and eluted with
dichloromethane. The combined elution was concentrated under
reduced pressure to give the crude reaction mixture for the d.r. value
determination (87:13), and was additionally purified by silica gel
column (n-hexane/ethyl acetate, v/v, 150:1) to give the desired
product as a white solid: 126 mg (cis), 19 mg (trans), 85% yield,
97% ee (cis).
Scheme 2. Concurrent kinetic resolution of the cyclopropane 2g.
obtained with the phenyl-substituted cyclopropane 2g. Both
the [3+2] cycloaddition product 6bg and the remaining
cyclopropane (S)-2g were isolated in nearly quantitative
yields and high optical purities (95% and 92% ee, respec-
tively, Scheme 2).
Received: January 3, 2013
Published online: March 4, 2013
With respect to the transformation of the [3+2] annula-
tion products, manipulations on the silyl and ester groups in
the product 3ga can be preformed without erosion of
enantiomeric purity (Scheme 3). The silyl protecting group
can be readily removed with HF/pyridine. In contrast, the two
ester groups can be selectively reduced. One ester can be
reduced with DIBAL-H/NaBH4 to give 7, which accommo-
dates four contiguous stereocenters. And both esters can be
reduced with LiAlH4 to give the diol 9. These transformations
showed that the current reaction is potentially useful in
organic synthesis.
In summary, a highly diastereo- and enantioselective
formal [3+2] cycloaddition reaction of cyclic enol silyl ethers
with D–A cyclopropanes was realized using modified cop-
per(II)/BOX catalysts, thus providing an efficient, new, and
facile access to a range of 3a-hydroxy [n.3.0]carbobicycles of
high optical purity. This reaction works well with five- to
Keywords: annulations · asymmetric catalysis · copper ·
fused-ring systems · small rings
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[1] a) J. L. Reino, R. Durꢁn-Patrꢂn, I. Segura, R. Hernꢁndez-Galꢁn,
H. H. Riese, I. G. Collado, J. Nat. Prod. 2003, 66, 344; b) A.
del C. Coronel, C. M. Cerda-Garcꢃa-Rojas, P. Joseph-Nathan,
C. A. N. Catalꢁn, Flavour Fragrance J. 2006, 21, 839; c) M. A. C.
Kaplan, H. R. L. Pugialli, D. Lopes, H. E. Cottlieb, Phytochem-
istry 2000, 55, 749; d) L. Villaescusa Castillo, A. M. D. Lanza, R.
Faure, L. Debrauwer, R. Elias, G. Guybalansard, Phytochemistry
1995, 40, 1193; e) R. Battaglia, M. D. Bernardi, G. Fornza, G.
Mellerio, G. Vidari, P. V. Finsi, J. Nat. Prod. 1980, 43, 319; f) J.-H.
Yang, J.-X. Pu, J. Wen, X.-N. Li, F. He, Y.-B. Xue, Y.-Y. Wang, Y.
Li, W.-L. Xiao, H.-D. Sun, J. Nat. Prod. 2010, 73, 12; g) S. Liang,
Y.-H. Shen, Y. Feng, J.-M. Tian, X.-H. Liu, Z. Xiong, W.-D.
Zhang, J. Nat. Prod. 2010, 73, 532; h) X. Wu, S. Lin, C. Zhu, Z.
4006 www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 4004 –4007

Angewandte
Chemie
Yue, Y. Yu, F. Zhao, B. Liu, J. Dai, J. Shi, J. Nat. Prod. 2010, 73,
1294.
i) C. Schꢄfer, M. Miesch, L. Miesch, Org. Biomol. Chem. 2012,
10, 3253.
[2] Radical cyclizations: a) A. G. Angoh, D. L. J. Clive, J. Chem.
Soc. Chem. Commun. 1985, 941; b) K. Miura, K. Fugami, K.
Oshima, K. Utimoto, Tetrahedron Lett. 1988, 29, 5135; c) M.
Nagai, J. Lazor, C. S. Wilcox, J. Org. Chem. 1990, 55, 3440;
d) V. H. Rawal, R. C. Newton, V. Krishnamurthy, J. Org. Chem.
1990, 55, 5181; e) S. Kim, S. Lee, J. S. Koh, J. Am. Chem. Soc.
1991, 113, 5106; f) S. Kim, J. S. Koh, J. Chem. Soc. Chem.
Commun. 1992, 1377; g) G. A. Molander, J. A. McKie, J. Org.
Chem. 1994, 59, 3186; h) G. A. Molander, S. R. Shakya, J. Org.
Chem. 1996, 61, 5885; i) S. Tsunoi, I. Ryu, S. Yamasaki, M.
Tanaka, N. Sonoda, M. Komatsu, Chem. Commun. 1997, 1889;
j) G. A. Molander, C. N. Wolfe, J. Org. Chem. 1998, 63, 9031;
k) K. Kakiuchi, Y. Fujioka, H. Yamamura, K. Tsutsumi, T.
Morimoto, H. Kurosawa, Tetrahedron Lett. 2001, 42, 7595; l) D.
Parmar, H. Matsubara, K. Price, M. Spain, D. J. Procter, J. Am.
Chem. Soc. 2012, 134, 12751.
[3] Ring-closing metathesis: a) G. S. Weatherhead, G. A. Cortez,
R. R. Schrock, A. H. Hoveyda, Proc. Natl. Acad. Sci. USA 2004,
101, 5805; b) M. S. Dowling, C. D. Vanderwal, J. Org. Chem.
2010, 75, 6908; c) C. Aouf, N. Galy, H. Doucet, M. Santelli, Appl.
Organomet. Chem. 2010, 24, 794; d) G. Mehta, S. Yaragorla,
Tetrahedron Lett. 2011, 52, 4485; e) F. Gao, C. T. M. Stamp, P. D.
Thornton, T. S. Cameron, L. E. Doyle, D. O. Miller, D. J.
Burnell, Chem. Commun. 2012, 48, 233.
[4] [2+2] annulations: a) R. D. Clark, K. G. Untch, J. Org. Chem.
1979, 44, 248; b) W. T. Brady, R. M. Lloyd, J. Org. Chem. 1979,
44, 2560; c) C. S. Pak, S. K. Kim, J. Org. Chem. 1990, 55, 1954;
d) W. A. Loughlin, M. A. McCleary, Org. Biomol. Chem. 2003, 1,
1347; e) K. Takasu, M. Ueno, K. Inanaga, M. Ihara, J. Org.
Chem. 2004, 69, 517; f) K. Takasu, S. Nagao, M. Ueno, M. Ihara,
Tetrahedron 2004, 60, 2071; g) K. Inanaga, K. Takasu, M. Ihara, J.
Am. Chem. Soc. 2005, 127, 3668; and catalytic asymmetric
variants: h) E. Canales, E. J. Corey, J. Am. Chem. Soc. 2007, 129,
12686; i) K. Ishihara, M. Fushimi, J. Am. Chem. Soc. 2008, 130,
7532; [3+2] Annulations: j) Y. Takahashi, K. Tanino, I. Kuwa-
jima, Tetrahedron Lett. 1996, 37, 5943; k) K. Masuya, K. Domon,
K. Tanino, I. Kuwajima, J. Am. Chem. Soc. 1998, 120, 1724.
[5] [3+2] annulations of enol ethers with cyclopropanes: a) K.
Saigo, S. Shimada, T. Shibasaki, M. Hasegawa, Chem. Lett. 1990,
1093; b) M. Komatsu, I. Suehiro, Y. Horiguchi, I. Kuwajima,
Synlett 1991, 771; c) Y. Horiguchi, I. Suehiro, A. Sasaki, I.
Kuwajima, Tetrahedron Lett. 1993, 34, 6077; d) K. Takasu, S.
Nagao, M. Ihara, Adv. Synth. Catal. 2006, 348, 2376; e) J. Fang, J.
Ren, Z. Wang, Tetrahedron Lett. 2008, 49, 6659; f) F. de Nan-
teuil, J. Waser, Angew. Chem. 2011, 123, 12281; Angew. Chem.
Int. Ed. 2011, 50, 12075.
[8] For more details, please see the Supporting Information. For
selected reviews on the applications of DBFOX and PYBOX in
asymmetric synthesis, see: a) G. Desimoni, G. Faita, P. Quadrelli,
Chem. Rev. 2003, 103, 3119; b) S. Kanemasa, K. Ito, Eur. J. Org.
Chem. 2004, 4741; c) P. K. Singh, V. K. Singh, Pure Appl. Chem.
2012, 84, 1651.
[9] For catalytic enantioselective cycloadditions of cyclopropanes,
see: a) M. P. Sibi, Z. Ma, C. P. Jasperse, J. Am. Chem. Soc. 2005,
127, 5764; b) Y.-B. Kang, X.-L. Sun, Y. Tang, Angew. Chem.
2007, 119, 3992; Angew. Chem. Int. Ed. 2007, 46, 3918; c) A. T.
Parsons, J. S. Johnson, J. Am. Chem. Soc. 2009, 131, 3122;
d) A. T. Parsons, A. G. Smith, A. J. Neel, J. S. Johnson, J. Am.
Chem. Soc. 2010, 132, 9688; e) B. M. Trost, P. J. Morris, Angew.
Chem. 2011, 123, 6291; Angew. Chem. Int. Ed. 2011, 50, 6167;
f) Y.-Y. Zhou, J. Li, L. Ling, S.-H. Liao, X.-L. Sun, Y.-X. Li, L.-J.
Wang, Y. Tang, Angew. Chem. 2013, 125, 1492; Angew. Chem.
Int. Ed. 2013, 52, 1452; For general reviews on D-A cyclo-
propanes, see: g) H.-U. Reissig, R. Zimmer, Chem. Rev. 2003,
103, 1151; h) C. A. Carson, M. A. Kerr, Chem. Soc. Rev. 2009, 38,
3051; i) P. Tang, Y. Qin, Synthesis 2012, 2969.
[10] For reviews on sidearm strategy, see: a) J. Zhou, Y. Tang, Chem.
Soc. Rev. 2005, 34, 664; b) L. H. Gade, S. Bellemin-Laponnaz,
Chem. Eur. J. 2008, 14, 4142; c) G. C. Hargaden, P. J. Guiry,
Chem. Rev. 2009, 109, 2505. For selected examples, see: d) J.
Zhou, Y. Tang, J. Am. Chem. Soc. 2002, 124, 9030; e) R.
Rasappan, M. Hager, A. Gissibl, O. Reiser, Org. Lett. 2006, 8,
6099; f) M. Seitz, C. Capacchione, S. Bellemin-Laponnaz, H.
Wadepohl, B. D. Ward, L. H. Gade, Dalton Trans. 2006, 193;
g) C. Foltz, M. Enders, S. Bellemin-Laponnaz, H. Wadepohl,
L. H. Gade, Chem. Eur. J. 2007, 13, 5994; h) C. Foltz, B. Stecker,
G. Marconi, S. Bellemin-Laponnaz, H. Wadepohl, L. H. Gade,
Chem. Eur. J. 2007, 13, 9912; i) A. Schꢄtz, R. Rasappan, M.
Hager, A. Gissibl, O. Reiser, Chem. Eur. J. 2008, 14, 7259; j) R.
Rasappan, T. Olbrich, O. Reiser, Adv. Synth. Catal. 2009, 351,
1961; k) M. Hager, S. Wittmann, A. Schꢄtz, F. Pein, P.
Kreitmeier, O. Reiser, Tetrahedron: Asymmetry 2010, 21, 1194.
[11] For recent uses of sidearm-modified BOX ligands, see: a) V. L.
Rendina, D. C. Moebius, J. S. Kingsbury, Org. Lett. 2011, 13,
2004; b) M. R. Castillo, S. Castillꢂn, C. Claver, J. M. Fraile, A.
Gual, M. Martꢃn, J. A. Mayoral, E. Sola, Tetrahedron 2011, 67,
5402; c) T. Sawada, M. Nakada, Tetrahedron: Asymmetry 2012,
23, 350; d) V. L. Rendina, H. Z. Kaplan, J. S. Kingsbury, Syn-
thesis 2012, 686; e) Y.-Y. Zhou, L.-J. Wang, J. Li, X.-L. Sun, Y.
Tang, J. Am. Chem. Soc. 2012, 134, 9066; f) J. Li, S.-H. Liao, H.
Xiong, Y.-Y. Zhou, X.-L. Sun, Y. Zhang, X.-G. Zhou, Y. Tang,
Angew. Chem. 2012, 124, 8968; Angew. Chem. Int. Ed. 2012, 51,
8838; g) C. Deng, L.-J. Wang, J. Zhu, Y. Tang, Angew. Chem.
2012, 124, 11788; Angew. Chem. Int. Ed. 2012, 51, 11620.
[12] In our initial investigation of ester groups, methyl and benzyl
esters were less selective, while tert-butyl ester was inert in the
reactions of 1g; see the Supporting Information.
[6] a) J.-P. Qu, C. Deng, J. Zhou, X.-L. Sun, Y. Tang, J. Org. Chem.
2009, 74, 7684; b) J.-P. Qu, Y. Liang, H. Xu, X.-L. Sun, Z.-X. Yu,
Y. Tang, Chem. Eur. J. 2012, 18, 2196.
[7] For other methods, see: a) D. Schinzer, M. Ruppelt, Chem. Ber.
1991, 124, 247; b) T. Shono, N. Kise, T. Fujimoto, N. Tominaga,
H. Morita, J. Org. Chem. 1992, 57, 7175; c) S. Janardhanam, K.
Rajagopalan, J. Chem. Soc. Perkin Trans. 1 1992, 2727; d) H.
Maeda, T. Maki, H. Ashie, H. Ohmori, J. Chem. Soc. Chem.
Commun. 1995, 871; e) A. Klein, M. Miesch, Tetrahedron Lett.
2003, 44, 4483; f) N. D. Litvinas, B. H. Brodsky, J. D. Bois,
Angew. Chem. 2009, 121, 4583; Angew. Chem. Int. Ed. 2009, 48,
4513; g) T. Liu, X. Zhao, L. Lu, T. Cohen, Org. Lett. 2009, 11,
4576; h) N. Saito, Y. Sugimura, Y. Sato, Org. Lett. 2010, 12, 3494;
[13] CCDC 917548 (3aa-cis), 917502 (3da-trans), and 917503 (3gc)
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
[14] The corresponding ring-opened products were isolated in
approximately 30% yield in the enol silyl ether form.
Angew. Chem. Int. Ed. 2013, 52, 4004 –4007
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