Highly diastereoselective synthesis of tetralin-fused spirooxindoles via lewis acid-catalyzed C(sp3)H bond functionalization

Article abstract of DOI:10.1246/cl.180275

A highly diastereoselective synthesis of tetralin-fused spirooxindole derivatives was described. Treatment of benzylidene oxindoles with a catalytic amount of Sc(OTf)₃ in refluxing hexane afforded the target compounds in good chemical yields with excellent diastereoselectivities (up to >20:1). Detailed investigation of the reaction mechanism revealed that both interconversion of the two diastereomers and their solubility difference in reaction medium were the key to achieving excellent diastereoselectivities.

Full text of DOI:10.1246/cl.180275

Advance Publication Cover Page
Highly Diastereoselective Synthesis of Tetralin-Fused Spirooxindoles via
Lewis Acid-Catalyzed C(sp3)–H Bond Functionalization
Mizuki Machida and Keiji Mori*
Advance Publication on the web April 27, 2018
doi:10.1246/cl.180275
© 2018 The Chemical Society of Japan
Advance Publication is a service for online publication of manuscripts prior to releasing fully edited, printed versions. Entire
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Publication manuscripts.

1
Highly Diastereoselective Synthesis of Tetralin-Fused Spirooxindoles via Lewis Acid-Catalyzed
C(sp3)–H Bond Functionalization
Mizuki Machida,1 and Keiji Mori*1
1Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho,
Koganei, Tokyo 184-8588
E-mail: k_mori@cc.tuat.ac.jp
1
2
3
4
5
6
7
8
9
A highly diastereoselective synthesis of tetralin-fused
spirooxindole derivatives was described. Treatment of
benzylidene oxindoles with a catalytic amount of Sc(OTf)3
in refluxing hexane afforded the target compounds in good
chemical yields with excellent diastereoselectivities (up to
>20:1). Detailed investigation of the reaction mechanism
revealed that both interconversion of the two diastereomers
and their solubility difference in reaction medium were the
key to achieving excellent diastereoselectivities.
49 polyheterocycles, including spirooxindoles and its analog
50 (spiroindolenins), based on this methodology.
51
52
53 Scheme 1. C(sp3)–H functionalization by the internal redox
10 Keywords: C–H bond functionalization, tatralin,
11 spirooxiindoles
54 process.
55
56
The preliminary and important example for the
12
Spirooxindoles with tetrasubstituted stereogenic
57 synthesis of these class of skeleton by internal redox
58 reaction was reported by Seidel and co-workers in 2011,10a
59 in which conjugate iminium species derived from indoles
60 (azafulvenium ions) were the key intermediate for
61 promoting the [1,5]-hydride shift process. Stimulated by the
62 results, Xu and Sun improved this reaction to the
63 diastereoselective synthesis of spiroindolenins.10b Yuan and
64 co-workers found that this methodology was effective tool
13 centers at 3-position are of particular interest because they
14 can be seen in many biologically active compounds and
15 many synthetic chemists have devoted much time and effort
16 to the development of efficient strategies for their
17 synthesis.1 Among the spirooxindole derivatives, there is
18 keen interest in other useful structures, such as pyrrolidine,
19 piperidine, and -carboline-fused analogs. The fact that
20 some of them have advanced into clinical trials has made
21 them even more attractive synthetic targets than ever.2
65 for
the
highly
diastereoselective
synthesis
of
66 tetrahydroquinoline-fused spirooxindoles as shown in
67 Scheme 2 (upper part).11a In 2015, asymmetric variant of
68 Yuan’s reaction was accomplished by Feng and co-workers
69 with chiral scandium complex.11b
22
Tetralins (tetrahydronaphthalenes) are found in many
23 bioactive molecules3 and the potent biological properties of
24 compounds possessing a tetralin and an oxindole hybrid
25 core are easy to imagine. However, to our surprise, very
26 few synthetic methods have been reported for tetralin-fused
27 spirooxindoles, especially for spirooxindole unit at 2-
28 position of the tetralin core. Connon’s group4 and Peng and
29 Huang’s group5 independently developed an effective
30 method to synthesize the target structure by adopting
31 Tamura cyclization and Michael/aldol sequence with 3-
70
As part of our recent efforts to develop new catalytic
71 C–H bond functionalization methodologies (internal redox
72 reaction),12 we have devised several effective methods for
73 the preparation of various tetralin derivatives.12c,d,i In the
74 early stage, this reaction system was limited to the
75 construction of tetralins with a single stereogenic center.12c,d
76 Quite recently, we found that highly diastereoselective
77 synthesis of 1,3-disubstituted tetralins was achievable.12i
78 Motivated by both our recent results and recent precedents
79 for the synthesis of spirooxindoles via internal redox
80 reaction, we turned our attention to the stereoselective
81 construction of tetralin-fused spirooxindoles with
82 contiguous stereogenic centers.
32 ylidene oxindole.
It was notable that the highly
33 diastereoselective syntheses of tetralin-fused spirooxindoles
34 with three contiguous stereogenic centers were realized in
35 both cases. Recently, Liu and Li’s group reported a highly
36 diastereoselective synthesis of the target molecule that
37 involved a FeCl3-mediated radical tandem reaction of 3-
38 benzyl-2-oxindoles with styrenes.6 Quite recently, Kesavan
39 and co-workers reported that the Hauser-Craus annulation
40 was also a reliable choice for synthesizing spirocarbocyclic
41 oxindoles.7
83
Herein we report a highly diastereoselective synthesis
84 of tetralin-fused spirooxindoles via Lewis acid-catalyzed
85 C(sp3)–H bond functionalization. Two factors are essential
86 to achieving excellent diastereoselectivity: (1) the
87 interconversion of two diastereomers, and (2) a large
88 solubility difference between the diastereomers in the
42
Recently, hydride shift triggered internal redox
43 reaction have been taken much interest because of its unique
44 features (Scheme 1): (1) transformation of inert, C(sp3)–H
45 bond without external oxidants, and (2) construction of
46 complex polycyclic frameworks from relatively simple
47 starting materials.8,9 The latter point stimulated many
48 chemists to the construction of various complex
89 reaction medium (hexane).
The low to moderate
90 diastereoselectivities after the initial product formation were
91 significantly improved by the solubility difference induced
92 diastereomer shift to afford various tetralin-fused

2
1
2
3
spirooxindoles in excellent diastereoselectivities (up to
>20:1).
41 shift process, that is, both benzyl phenethyl ether derivative
42 (O-analog) and p-methoxyphenethyl derivative (C-analog)
43 did not afford the desired adducts completely.
44
45 Table 1. Examination of reaction conditions.
46
Run
Catalyst
Solvent
Yield
(%)
D.r.a
1
2
Yb(OTf)3
Gd(OTf)3
Hf(OTf)4
Mg(OTf)2
Sc(OTf)3
TiCl4
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
toluene
92
99
97
86
95
95
81
98
99
2.0:1
2.0:1
1.2:1
2.3:1
2.9:1
2.6:1
2.3:1
1.5:1
3.5:1
4.6:1
3
4
5
6
7
SnCl4
4
5
6
7
8
Sc(OTf)3
Sc(OTf)3
Sc(OTf)3
Scheme 2. Highly diastereoselective synthesis of tetralin-
fused spirooxindoles by Lewis acid-catalyzed C(sp3)–H
bond functionalization.
9
p-xylene
10
benzotrifluorid 90
e
8
9
Benzylidene oxindole derivative 1a with an N,N-
dibenzyl ethyl amine moiety at ortho-position was selected
11
12
Sc(OTf)3
Sc(OTf)3
cyclohexane
hexane
98
96
15:1
10 as the substrate because of its potentially high reactivity.12f
11 Table 1 illustrates the results of examination of the reaction
12 conditions. When a solution of 1a13 in ClCH2CH2Cl was
13 treated with 10 mol % of Yb(OTf)3, which showed excellent
14 catalytic performance in our previous study (1-aminoindane
15 formation reaction from benzylamine derivatives),12f the
16 desired reaction proceeded smoothly to afford adduct 2a in
17 excellent chemical yield with low diastereoselectivity (92%,
18 d.r. = 2.0:1). Gd(OTf)3 was also effective but the
19 diastereoselectivity remained low (d.r. = 2.0:1, entry 2).
20 Both Hf(OTf)4 and Mg(OTf)2 also afforded desired adduct
>20:1
a
47
Diastereomeric ratio was determined by comparing the
48 integration value of the NH proton of oxindole moiety for each
49 diastereomer in the 1H NMR spectra.
50
Fortunately, the two diastereomers were separable by
51 silica-gel column chromatography and so we could examine
52 the reversibility of the reaction by subjecting each
53 diastereomer (2aa and 2ab) to the optimized reaction
54 conditions (entry 12, Table 1). These experiments gave two
55 important pieces of information to understand the dramatic
56 solvent effect of hexane (Scheme 3). First, the same
57 diastereomeric ratio was obtained from both diastereomers
58 and 2aa was obtained exclusively (2aa:2ab = >20:1), which
59 clearly indicated the reversibility of the reaction. Second,
60 the solubility of 2aa and 2ab in hexane was completely
61 different, that is, whereas minor diastereomer 2ab was
62 easily solubilized in refluxing hexane, major diastereomer
63 2aa was not soluble at all. When 2ab was subjected to the
64 reaction conditions, the reaction mixture became a clear
65 solution immediately (in less than 5 min) and a suspension
66 24 h later. In sharp contrast, the reaction mixture remained
67 a suspension with 2aa until the end of the reaction (24 h). It
68 is worthy to note that the situation was markedly different in
69 ClCH2CH2Cl, which exhibited low diastereoselectivity
70 (d.r.= 2.9:1, entry 5, Table 1). The reaction mixture
71 maintained a clear solution from the start to the end of the
72 reaction for both diastereomers, and the same
73 diastereomeric ratio was obtained (2aa:2ab = 2.5:1). These
74 results suggest that the excellent diastereoselectivity in this
21 2a
in
excellent
chemical
yields
with
low
22 diastereoselectivities (entries 3 and 4, d.r. = 1.2–2.3:1).
23 Sc(OTf)3 resulted in a slightly improved diastereoselectivity
24 of 2.9:1 while maintaining excellent chemical yield (95%,
25 entry 5). Well-known and inexpensive strong Lewis acids,
26 such as TiCl4 and SnCl4 afforded 2a in good chemical yields
27 with low diastereoselectivities (d.r. = 2.3–2.6:1, entries 6
28 and 7).
29
Next, the reaction solvent was examined with Sc(OTf)3
30 as the catalyst, which offered quite interesting results.
31 Diastereoselectivity was dramatically changed by the
32 reaction solvent. Whereas diastereoselectivity was slightly
33 decreased in toluene (d.r. = 1.5:1, entry 8), moderate
34 selectivity was achieved in benzotrifluoride (d.r. = 4.6:1,
35 entry 10). In particular, less polar solvents dramatically
36 improved diastereoselectivity and hexane turned out to be
37 the best. One diastereomer was obtained exclusively (d.r. =
38 >20:1, entry 12).
39
The strong electron-donating ability of the amine
40 moiety was indispensable to promote the desired hydride

3
1
2
3
4
reaction might not be a result of thermodynamic control, in
contrast to our recent report of the highly diastereoselective
synthesis of 1,3-disubstituted tetralins.12i
37 yields with high to excellent diastereoselectivities (86–99%,
38 d.r. = 7.1–>20:1). On the other hand, naphthyl-type product
39 2k was obtained with moderate diastereoselectivity even in
40 hexane (d.r. = 5.1:1), which was ascribed to the decreased
41 solubility difference between the two diastereomers. In all
42 cases, employment of hexane as the reaction solvent was the
43 key to achieving excellent diastereoselectivities, and low
44 diastereoselectivities were observed when the reactions
45 were conducted in ClCH2CH2Cl.17
The
relative
46 stereochemistries of major isomers were surmised as shown
47 in Table 1, Schemes 1–3, and Figure 1 by analogy to 2aa
48 and 2c, whose relative stereochemistries were
49 unambiguously established by X-ray crystallographic
50 analysis.18
51
5
6
7
8
9
Scheme 3. Examination of the reversibility of the reaction.
Based on the above results, the excellent
diastereoselectivity of the reaction was rationalized as
10 follows (Scheme 4): two diastereomers 2aa and 2ab
11 interconverted easily under Sc(OTf)3 catalysis through ring-
12 opening and ring-closing processes via B, and there was
13 only
14 diastereomers according to the results with ClCH2CH2Cl
15 (vide supra). The key to achieving the excellent
a
small thermodynamic bias between these
16 diastereoselectivity is the solubility difference between the
17 diastereomers in hexane. The low solubility of 2aa in
18 hexane induced solidification, which led to the consumption
19 of 2ab by the redistribution of equilibrium. Repeating this
20 process (solidification/redistribution of equilibrium) resulted
21 in the accumulation of 2aa in the solid form, and as a result,
22 excellent diastereoselectivity was achieved.14, 15, 16
23
24
25 Scheme 4. Rationale for high diastereoselectivity.
26
27
52
The substrate scope of this reaction is summarized in
53 Figure 1. Substrate scope.
28 Figure 1. Both excellent chemical yields and excellent
29 diastereoselectivities were achieved in the case of oxindole
30 derivatives 2b–d possessing various substituents such as Me
31 and Cl groups at 5 or 6-position of the oxindole unit (86–
32 95%, d.r. = >20:1). The electronic nature of the aromatic
33 ring of the tetralin core was almost negligible in this
34 reaction. Substrates 1e–j with electron-donating groups
35 (Me and OMe) and an electron-withdrawing group (F)
36 afforded corresponding adducts 2e–j in excellent chemical
54
55
In summary, we have developed
a
highly
56 diastereoselective synthesis of tetralin-fused spirooxindoles
57 via Lewis acid-catalyzed C(sp3)–H bond functionalization.
58 Various substituents, such as electron-donating and
59 electron-withdrawing groups on the aromatic ring, had an
60 almost negligible effect on the reaction, and corresponding
61 adducts 2a–j were obtained in good to excellent chemical

4
68
J. Am. Chem. Soc. 2009, 131, 3166. g) J. C. Ruble, A. R. Hurd, T.
A. Johnson, D. A.; Sherry, M. Barbachyn, R. P. L. Toogood, G.
L. Bundy, D. R. Graber, G. M. Kamilar, J. Am. Chem. Soc. 2009,
131, 3991. h) M. J. Mahoney, D. T. Moon, J. Hollinger, E.
Fillion, Tetrahedron Lett. 2009, 50, 4706. i) P. A. Vadola, D.
Sames, J. Am. Chem. Soc. 2009, 131, 16525. j) G. Zhou, J.
Zhang, Chem. Commun. 2010, 46, 6593. k) I. D. Jurberg, B.
Peng, E. Wöstefeld, M. Wasserloos, N. Maulide, Angew. Chem.
Int. Ed. 2012, 51, 1950. l) X. Gao, V. Gaddam, E. Altenhofer, R.
R. Tata, Z. Cai, N. A. Yongpruksa, K. Garimallaprabhakaran, M.
Harmata, Angew. Chem. Int. Ed. 2012, 51, 7016. m) D.-F. Chen,
Z.-Y. Han, Y.-P. He, J. Yu, L.-Z. Gong, Angew. Chem. Int. Ed.
2012, 51, 12307. n) S. Shaaban, N. Maulide, Synlett 2013, 1722.
o) A. Dieckmann, M. T. Richers, A. Y. Platonoova, C. Zhang, D.
Seidel, N. K. Houk, J. Org. Chem. 2013, 78, 4132. p) A. Vidal,
M. Martin-Luna, M. Alajarin, Eur. J. Org. Chem. 2014, 878. q)
Y.-Z. Chang, M.-L. Li, W.-F. Zhao, X. Wen, H. Sun, Q.-L. Xu, J.
Org. Chem. 2015, 80, 9620. r) C. W. Suh, S. J. Kwon, D. Y. Kim,
Org. Lett. 2017, 19, 1334. s) S.-S. Li, L. Zhou, L. Wang, H.
1
2
3
4
5
6
7
8
9
yields with excellent diastereoselectivities (up to >20:1).
Detailed investigation of the reaction mechanism revealed
two key points for the excellent diastereoselectivity: (1)
interconversion of the two diastereomers, and (2) a large
solubility difference in hexane. Further investigations of the
diastereoselective construction of polycycles by means of a
hydride shift/cyclization system are underway in our
laboratory and the results will be reported in due course.
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10 Supporting
11 http://dx.doi.org/10.1246/cl.******.
Information
is
available
on
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12 References and Notes
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20
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24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
1
For recent reviews on the synthesis of spirooxindoles, see: a) C.
V. Galliford, K. A. Scheidt, Angew. Chem. Int. Ed., 2007, 46,
8748. b) B. M. Trost, M. K. Brennan, Synthesis 2009, 3003. c) F.
Zhou, Y.-L. Liu, J. Zhou, Adv. Synth. Catal. 2010, 352, 1381. d)
N. R. Ball-Jones, J. J. Badillo A. K. Franz, Org. Biomol. Chem.
2012, 10, 5165. e) L. Hong, R. Wang, Adv. Synth. Catal. 2013,
355, 1023. f) D. Cheng, Y. Ishihara, B. Tan, C. F. Barbas III,
ACS Catal. 2014, 4, 743. ꢀ
84
85
86
87
Zhao, L. Yu, J. Xiao, Org. Lett. 2018, 20, 138.
88 10
89
For the synthesis of tetrahydroquinoline fused-spiroindoles by
internal redox reaction, see: a) M. C. Hablich, I. Deb, C. Kanta
De, D. Seidel, J. Am. Chem. Soc. 2011, 133, 2100. b) P.-F. Wang,
C.-H. Jiang, X. Wen, Q.-L. Xu, H. Sun, J. Org. Chem. 2015, 80,
1155.
90
91
2
a) M. Rottmann, C. McNamara, B. K. S. Yeung, M. C. S. Lee, B.
Zou, B. Russell, P. Seitz, D. M. Plouffe, N. V. Dharia, J. Tan, S.
B. Cohen, K. R. Spencer, G. E. González-Páez, S. B.
Lakshminarayana, A. Goh, R. Suwanarusk, T. Jegla, E. K.
Schmitt, H. P. Beck, R. Brun, F. Nosten, L. Renia, V. Dartois, T.
H. Keller, D. A. Fidock, E. A. Winzeler, T. T. Diagana, Science,
2010, 329, 1175. b) S. Y. Leong, P. W. Smith, B. Zou, Chin. J.
Chem. 2014, 32, 1217. c) S. Wang, W. Sun, Y. Zhao, D.
McEachern, I. Meaux, C. Barrière, J. A. Stuckey, J. L. Meagher,
L. Bai, L. Liu, C. G. Hoffman-Luca, J. Lu, S. Shangary, S. Yu, D.
Bernard, A. Aguilar, O. Dos-Santos, L. Besret, S. Guerif, P.
Pannier, D. Gorge-Bernat, L. Debussche, Cancer Res. 2014, 74,
5855. ꢀ
92
93 11
94
For the synthesis of tetrahydroquinoline fused-spirooxindoles by
internal redox reaction, see: a) Y.-Y. Han, W.-Y. Han, X. Hou,
X.-M. Zhang, W.-C. Yuan. Org. Lett. 2012, 14, 4054.
Asymmetric version, see: b) W. Cao, X. Liu, J. Guo, L. Lin, X.
Feng, Eur. Chem. J. 2015, 21, 1632.
95
96
97
98 12
99
For the internal redox reaction developed by our group, see: a) K.
Mori, Y. Ohshima, K. Ehara, T. Akiyama, Chem. Lett. 2009, 38,
524. b) K. Mori, T. Kawasaki, S. Sueoka, T. Akiyama, Org. Lett.
2010, 12, 1732. c) K. Mori, S. Sueoka, T. Akiyama, J. Am. Chem.
Soc. 2011, 133, 2424. d) K. Mori, S. Sueoka, T. Akiyama, Chem.
Lett. 2011, 40, 1386. e) K. Mori, T. Kawasaki, T. Akiyama, Org.
Lett. 2012, 14, 1436. f) K. Mori, K. Kurihara, T. Akiyama, Chem.
Commun. 2014, 50, 3729. g) K. Mori, K. Kurihara, S. Yabe, M.
Yamanaka, T. Akiyama, J. Am. Chem. Soc. 2014, 136, 3744. h)
K. Mori, N. Umehara, T. Akiyama, Adv. Synth. Catal. 2015, 357,
901. i) T. Yoshida, K. Mori, Chem. Commun. 2017, 53, 4319;
For an asymmetric version of internal redox reaction catalyzed
by chiral phosphoric acid, see: j) K. Mori, K. Ehara, K. Kurihara,
T. Akiyama, J. Am. Chem. Soc. 2011, 133, 6166.
100
101
102
103
104
105
106
107
108
109
110
111
3
For some natural products and pharmaceuticals containing
tetralin scaffold, see: a) O. Pinto, J. Sardinha, P. D. Vaz, F.
Piedade, M. J. Calhorda, R. Abramovitch, N. Nazareth, M. Pinto,
M. S. J. Nascimento, A. P. Rauter, J. Med. Chem. 2011, 54, 3175.
b) M. Kvasnica, L. Rarova, J. Oklestkova, M. Budesinsky L.
Kohout, Bioorg. Med. Chem. 2012, 20, 6969. c) J. H. Soper, S.
Sugiyama, K. Herbst-Robinson, M. J. James, X. Wang, J. Q.
Trojanowski, A. B. Smith III, V. M. Y. Lee, C. Ballatore, K. R.
Brunden, ACS Chem. Neurosci. 2012, 3, 928. d) M. J. Hatfield, L.
G. Tsurkan, J. L. Hyatt, C. C. Edwards, A. Lemoff, C. Jeffries, B.
Yan, P. M. Potter, J. Nat. Prod. 2013, 76, 36. e) Gamal-Eldeen,
M.; Hamdy, N. A.; Abdel-Aziz, H. A.; El-Hussieny, E. A.; Fakhr,
I. M. I. Eur. J. Med. Chem. 2014, 77, 323.
112 13 The geometry of 1a was determined to be E by X-ray
crystallographic analysis.
113
114 14 Employment of NH-free substrate 1, which has low solubility in
115
116
117
118
hexane, was important to achieve excellent diastereoselectivity.
When the reaction was conducted with more lipophilic N-Bn
analog 3, the diastereomeric ratio remained low even with
hexane (d.r. = 2.5:1).
4
5
F. Manoni, S. J. Connon, Angew. Chem. Int. Ed. 2014, 53, 2628.
B. Wang, H.-J. Leng, X.-Y. Yang, B. Han, C.-L. Rao, L. Liu, C.
Peng, W. Huang, RSC. Adv. 2015, 8, 88272.
6
H.-R. Wu, L. Cheng, D.-L. Kong, H.-Y. Huang, C.-L. Gu, L. Liu,
D. Li, Wang, C.-J.. Org. Lett. 2016, 18, 1382.
7
8
K. Lokesh, V. Kesavan, Eur. J. Org. Chem. 2017, 5689.
For recent reviews on internal redox process, see: a) M. Tobisu,
N. Chatani, Angew. Chem. Int. Ed. 2006, 45, 1683. b) S. C. Pan,
Beilstein J. Org. Chem. 2012, 8, 1374. c) M. Wang,
ChemCatChem 2013, 5, 1291. d) B. Peng, N. Maulide, Chem,
Eur. J. 2013, 19, 13274. e) L. Wang, J. Xiao, Adv. Synth. Catal.
2014, 356, 1137. f) M. C. Haibach, D. Seidel, Angew. Chem. Int.
Ed. 2014, 53, 5010. g) S. J. Kwon, D. Y. Kim, Chem. Rec. 2016,
16, 1191.
119
120 15 Excellent diastereoselectivity was also achieved even with
121
Yb(OTf)3, Gd(OTf)3, and Hf(OTf)4 in hexane.
122 16 High electron donating ability of alkylamine moiety would be
important for promoting the retro-aldol reaction
124 17 Attempts to extend the present reaction to the catalyzed,
123
9
For selected examples of internal redox reactions, see: a) S. J.
Pastine, K. M. McQuaid, D. Sames, J. Am. Chem. Soc. 2005, 127,
12180. b) S. J. Pastine, D. Sames, Org. Lett. 2005, 7, 5429. c) A.
Polonka-Bálint, C. Saraceno, K. Ludányi, A. Bényei, P. Mátyus,
Synlett 2008, 2846. d) C. Zhang, S. Murarka, D. Seidel, J. Org.
Chem. 2009, 74, 419. e) K. M. McQuaid, D. Sames, J. Am. Chem.
Soc. 2009, 131, 402. f) D. Shinkai, H. Murase, T. Hata, H. Urabe,
125
126
127
enantioselective reaction with chiral Sc-complex (with several
Py-BOX ligands) were unsuccessful and 2aa was obtained in
the racemic form.
128 18 CCDC-1818264, 1818265, and 1818266 contains the
129
130
supplementary crystallographic data of 1a, 2aa, and 2a (See SI
for details). This data can be obtained free of charge from The

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www.ccdc.cam.ac.uk/data_request.
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Data
Center
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