Development of a new spiro-BOX ligand and its application in highly enantioselective palladium-catalyzed cyclization of 2-iodoanilines with allenes

Article abstract of DOI:10.1002/adsc.200900607

In this communication, we report the syn-thesis of a new chiral spiro-bisoxazoline ligand, i.e., β-naphthylmethyl-substituted spiro-BOX [(R₀,S,S)-L7] and have successfully applied it to the palladi-um-catalyzed enantioselective cyclization reac

Full text of DOI:10.1002/adsc.200900607

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DOI: 10.1002/adsc.200900607
Development of a New Spiro-BOX Ligand and Its Application
in Highly Enantioselective Palladium-Catalyzed Cyclization of
2-Iodoanilines with Allenes
Wei Shu,a Qiong Yu,b and Shengming Maa,b,*
a
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 354 Fenglin Lu, Shanghai 200032, Peopleꢀs Republic of China
Fax : (+86)-21-6260-9305; e-mail: masm@mail.sioc.ac.cn
Shanghai Key Laboratory of Green Chemistry and Chemical Process, Department of Chemistry, East China Normal
b
University, 3663 North Zhongshan Road, Shanghai 20062, Peopleꢀs Republic of China
Received: August 13, 2009; Revised: September 3, 2009; Published online: November 18, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900607.
Abstract: In this communication, we report the syn-
thesis of a new chiral spiro-bisoxazoline ligand, i.e.,
b-naphthylmethyl-substituted spiro-BOX [(Ra,S,S)-
L7] and have successfully applied it to the palladi-
um-catalyzed enantioselective cyclization reaction
of simple allenes with o-aminoiodobenzenes, afford-
ing highly optically active 3-alkylideneindolines in
good yields with excellent enantiomeric excesses.
Keywords: allenes; asymmetric catalysis; cycliza-
tion; indolines; palladium
Scheme 1. Two different protocols of enantioselective allyla-
tion.
Due to the potentials of compounds with chirality,
asymmetric synthesis has always been a hot research to moderate ee have been reported.[4] Larock et al. re-
area for organic chemists. In addition to the well-rec- ported the cyclization of 2-aminophenyl iodides with
ognized asymmetric reactions of C=C bonds such as allenes catalyzed by Pd-(R)-Bn-BOX [(R)-L1] to
hydrogenation, epoxidation, etc., scientists are pursu- afford a series of indolines in 80–82% ee;[5] This
ing the efficient access to optically active compounds ligand has also been used by us to synthesize other
via catalytic enantioselective C C and C X bond for- heterocycles again with 80–84% ee.[6] We have tried
mation processes. In this area, transition metal-cata- many known ligands during the past ten years for this
lyzed asymmetric allylic substitution, especially the type of transformation with very limited success, thus,
Tsuji–Trost reaction, has been demonstrated to be in order to make this type of transformation syntheti-
one of the most powerful protocols to form these cally useful and practical, new effective ligands should
bonds with excellent enantioselectivity.[1] In principle, be developed. In a case like this, there is really no
the carbometallation of allenes would usually provide substitute for the human labour required to identify
2-substituted p-allylic metallic intermediates,[2] which new ligands. Thus, we pursued new bisoxazoline li-
provides a new pathway for asymmetric synthesis gands from other commercially available amino acids.
using allenes as the starting points (Scheme 1). How- Herein, we wish to report the development of a new
ever, the successful reports on the asymmetric allylic ligand, i.e., b-naphthylmethyl spiro-BOX (L7), which
substitution with a 2-substituted p-allylic palladium in- has been demonstrated for the enantioselective Pd-
termediate are still very limited,[3] thus, as expected, catalyzed cyclization of 2-iodoanilines with allenes, af-
only a few examples on the asymmetric allylic substi- fording a wide range of 2H-indolines in good yields
tution based on carbometallation of allenes with low with 94–98% ee (Figure 1).
À
À
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Wei Shu et al.
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Figure 1. Evolution of the bisoxazoline ligands.
We started our investigation based on the reaction (86%) was observed.[8] Luckily, to our surprise, we ob-
of 1a with 2a in DMF catalyzed by 5 mol% Pd(dba)2 served that when (Ra,S,S)-L7 with a b-naphthylmethyl
AHCTUNGTRENNUNG
with 5 mol% (Ra,S,S)-L2 having a chiral spiro-skele- substituent was applied to the reaction under the same
ton[7] as the ligand. To our disappointment, the de- conditions, the ee value was improved to 90%
sired product was obtained in 74% yield with 79% ee (Table 1, entry 7). Quick screening on the solvent
(Table 1, entry 1). Ligand (Sa,S,S)-L2 led to the (S)- effect revealed that THF is the best (Table 1, en-
product in 70% ee (entry 2, Table 1). Further screen- tries 7–11). Increasing the reaction temperature can
ing of the ligands revealed that the phenyl- and iso- shorten the reaction time and surprisingly improve
propyl-substituted spiro-BOX ligands [(Ra,S,S)-L3 the yield without eroding the enantioselectivity
and L4] led to an almost racemic product (Table 1, (Table 1, entry 12). Further increasing the ratio of
entries 3 and 4). Interestingly, methyl-substituted 1a:2a to 1:4 led to a complete consumption of 1a and
spiro-BOX [(Ra,S,S)-L5] afforded 3aa in 87% ee 3aa was obtained in 57% yield with 96% ee (Table 1,
(Table 1, entry 5). When the a-naphthylmethyl group entry 14)! We then defined the reaction of 1 equiva-
substituted spiro-BOX [(Ra,S,S)-L6] was introduced lent of 1a and 4 equivalents of 2a catalyzed by
to this reaction, the same level of enantioselectivity 5 mol% PdACTHUNGTRNEUNG(dba)2 and 5 mol% (Ra,S,S)-L7 with
Table 1. Optimization of the reaction conditions for the Pd(0)-catalyzed enantioselective cyclization reaction of 1a with 2a.[a]
Entry
Ligand
Solvent
T [oC]
t [h]
Yield of 3aa [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
U
DMF
DMF
DMF
DMF
DMF
DMF
DMF
toluene
DCE
THF
90
90
90
90
90
90
90
90
90
90
90
110
110
110
24
10
37
18
32
24
22
36
36
86
65
48
48
48
74
79
À70
16
9
66 (17)
60 (21)
75
76
87
87
90
82
68
97
95
95
95
96
59 (15)
67 (15)
68 (17)
42 (39)
34 (43)
31 (40)
36 (40)
46 (16)
57
9
10
11
12
13[d]
14[e]
dioxane
THF
THF
THF
[a]
The reaction was carried out by using 0.2 mmol of 1a, 0.4 mmol of 2a, 0.08 mmol of Ag3PO4, 5 mol% of Pd
5 mol% of ligand in 2 mL of indicated solvent in a Schlenk tube with a screw cap unless otherwise stated.
Isolated yields, the yields in parentheses are the recoveries of 1a.
The ee values were determined by chiral HPLC analysis.
0.6 mmol of 2a were used.
0.8 mmol of 2a were used.
ACHTUNGRTENN(UNG dba)2, and
[b]
[c]
[d]
[e]
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Development of a New Spiro-BOX Ligand and Its Application
Table 2. Substrate scope of the Pd(0)-catalyzed enantioselective cyclization of various 1 with allenes 2.[a]
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57%, 96% ee (3aa)
76%, 95% ee (3ad)
87%, 97% ee (3ab)
69%, 95% ee (3ae)
52%, 96% ee (3ac)
79%, 96% ee (3af)
67%, 95% ee (3ag)
63%, 95% ee (3aj)
53%, 98% ee (E-3ah)
69%, 95% ee (3ak)
63%, 95% ee (3ai)
78%, 95% ee (3ba)
69%, 94% ee (3ca)
56%, 94% ee (E-3bh)
76%, 95% ee (3bf)
[a]
The reaction was carried out by using 0.2 mmol of 1, 0.8 mmol of 2, 0.08 mmol of Ag3PO4, 5 mol% of PdACHTNUGTRENUNG(dba)2, and
5 mol% of (Ra,S,S)-L7 in 2 mL of THF in a Schlenk tube with a screw cap. The yields given are isolated yields. The ee
values were determined by chiral HPLC analysis.
0.4 equivalents of Ag3PO4 as base in THF at 1108C as The configuration of the double bond is confirmed by
the standard conditions for further study.
an nOe study of 3ah (Figure 2). Besides N-(2-iodo-
With the optimized reaction conditions in hand, we phenyl)-4-methylbenzenesulfonamide, 4-F or 5-Cl
turned to examine the substrate scope of this process. substitution on the phenyl ring is also suitable in this
The results are listed in Table 2. Various terminal al- reaction, leaving further opportunity for elaboration.
lenes are proper substrates for this process, affording
In summary, we have developed a new spiro-BOX
corresponding (R)-2-alkylideneindolines[9] in moder- ligand, i.e., (Ra,S,S)-L7, and demonstrated its success-
ate to good yields with 94–98% ee. Notably, many ful application in the Pd-catalyzed asymmetric allylic
functional groups, such as ether, amide, and MOM, annulation of readily available 2-iodoanilines with al-
were easily tolerated in this reaction. 1,3-Disubstitut- lenes[10] affording the potentially useful 3-alkylidene-
ed allenes are also compatible in this asymmetric cy-
ACHTUNGTRENNUNGclization, giving the E-products 3ah and 3bh highly antiomeric excesses (94–98% ee). This type of ligand
indolines[11,12] in good yields with high to excellent en-
ACHTUNGTRENNUNG
stereoselectively in moderate yields with very high ee. may show potential in highly enantioselective con-
structions of a variety of cyclic compounds with po-
tentials based on carbometalation of allenes and
other bisoxazoline ligand-promoted asymmetric reac-
tions. Further investigations in this area, especially
the scope of different organic halides/nucleophiles
(Scheme 1) and application in other classic reactions,
are ongoing in our laboratory.
Figure 2. NOE study of (R)-E-3ah.
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Wei Shu et al.
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Experimental Section
ganic Synthesis, (Eds: E.-I Negishi, A. de Meijere),
Wiley-Interscience, New York, 2002, p 1491; b) S. Ma,
Pure Appl. Chem. 2006, 78, 197; c) T. Bai, S. Ma, G.
Jia, Coord. Chem. Rev. 2009, 253, 423.
Typical Procedure for the Preparation of (R)-3
To a Schlenk tube with a screw cap were added PdACTHNUTRGNEUNG(dba)2
[3] a) B. M. Trost, M. K. Brennan, Org. Lett. 2007, 9, 3961;
b) R. Shintani, S. Park, F. Shirozu, M. Murakami, T.
Hayashi, J. Am. Chem. Soc. 2008, 130, 16174; c) K.
Zhang, Q. Peng, X.-L. Hou, Y.-D. Wu, Angew. Chem.
2008, 120, 1765; Angew. Chem. Int. Ed. 2008, 47, 1741.
[4] a) K. Hiroi, F. Kato, A. Yamagata, Chem. Lett. 1998,
397; b) K. Hiroi, Y. Hiratsuka, K. Watanabe, I. Abe, F.
Kato, M. Hiroi, Tetrahedron: Asymmetry 2002, 13,
1351.
[5] a) R. C. Larock, J. M. Zenner, J. Org. Chem. 1995, 60,
482; b) J. M. Zenner, R. C. Larock, J. Org. Chem. 1999,
64, 7312.
[6] a) S. Ma, Z. Shi, S. Wu, Tetrahedron: Asymmetry 2001,
12, 193; b) W. Shu, Q. Yang, G. Jia, S. Ma, Tetrahedron
2008, 64, 11159.
(6 mg, 0.011 mmol), (Ra,S,S)-L7 (7 mg, 0.011 mmol), and
1 mL of THF. The resulting mixture was stirred for 2 h at
room temperature, which was followed by sequential intro-
duction of Ag3PO4 (34 mg, 0.081 mmol), 1a (75 mg,
0.20 mmol), 2a (112 mg, 0.81 mmol), and 1 mL of THF at
room temperature. The resulting solution was stirred at
1108C. When the reaction was completed as monitored by
TLC, the solvent was evaporated under vacuum, and the
residue was purified by chromatography on silica gel
(eluent: petroleum ether:ethyl acetate=70:1) to afford (R)-
3aa as an oil; yield: 44 mg (57%); 96% ee determined by
HPLC analysis [Chiralcel AD-H, hexane/i-PrOH=85/15,
0.7 mLminÀ1, 230 nm)]: tR=4.8 min (minor), 6.6 min
(major); [a]2D0: +9.4 (c 0.50, EtOAc); 1H NMR (400 MHz,
acetone-d6): d=7.72 (d, J=8.4 Hz, 1H), 7.61 (d, J=8.4 Hz,
2H), 7.44 (dd, J=7.6, 0.4 Hz, 1H), 7.36–7.30 (m, 1H), 7.26
(d, J=8.0 Hz, 2H), 7.11–7.05 (m, 1H), 5.48 (d, J=2.0 Hz,
1H), 4.99 (d, J=2.0 Hz, 1H), 4.80–4.75 (m, 1H), 2.31 (s,
3H), 2.12–2.04 (m, 1H), 1.86–1.76 (m, 1H), 1.47–1.21 (m,
10H), 0.86 (t, J=6.8 Hz, 3H); 13C NMR (100.5 MHz, ace-
tone-d6): d=146.1, 145.1, 144.9, 135.4, 131.3, 130.8, 130.4,
128.1, 125.3, 121.9, 117.4, 103.5, 67.3, 37.9, 32.5, 30.4, 29.9,
23.5, 23.2, 21.3, 14.3; MS (EI): m/z (%)=384 (M+ +1,
10.27), 383 (M+, 38.49), 144 (100); IR (neat): n=2954, 2926,
2856, 1599, 1494, 1454, 1372, 1306, 1292, 1229, 1187, 1172,
1153, 1120, 1093, 1021 cmÀ1; HR-MS: m/z=383.1918, calcd.
for C23H29NO2S (M+): 383.1919.
[7] Zhou et al. has recently successfully applied spiro-BOX
in copper-catalyzed highly enantioselective insertion of
À
À
carbenoids into O H and N H bonds, see: a) B. Liu,
S.-F. Zhu, W. Zhang, C. Chen, Q.-L. Zhou, J. Am.
Chem. Soc. 2007, 129, 5834; b) C. Chen, S.-F. Zhu, B.
Liu, L.-X. Wang, Q.-L. Zhou, J. Am. Chem. Soc. 2007,
129, 12616; c) S.-F. Zhu, C. Chen, Y. Cai, Q.-L. Zhou,
Angew. Chem. 2008, 120, 946; Angew. Chem. Int. Ed.
2008, 47, 932.
[8] For application of a-naphthylmethy-substituted ana-
logues, see: W. Shu, S. Ma, Chem. Commun. 2009,
6198.
[9] The configuration is confirmed to be R by comparation
of the specific rotation of 3af with the data reported in
ref.[5b] See the Supporting Information for more details.
[10] a) K.M. Brummond, J. E. DeForrest, Synthesis 2007,
795; b) P. Rona, P. Crabbꢂ, J. Am. Chem. Soc. 1969, 91,
3289; c) J. Kuang, S. Ma, J. Org. Chem. 2009, 74, 1763;
d) J. Li, C. Zhou, C. Fu, S. Ma, Tetrahedron 2009, 65,
3695.
[11] a) P. M. Dewick, Medicinal Natural Products: A Bio-
synthetic Approach, 2nd edn., John Wiley, New York,
2002; b) F. Gueritte, J. Fahy, in: Anticancer Agents
from Natural Products, (Eds: G. M. Cragg, D. G. I.
Kingston, D. J. Newman), CRC Press: Boca Raton, FL,
2005, p 123.
Acknowledgements
Financial support from National Natural Science Foundation
of China (20732005), State Basic Research and Development
Program (Grant No. 2006CB806105), and Chinese Academy
of Sciences is greatly appreciated. We thank Prof. Qi-Lin
Zhou for generous gifts of ligands L3–L6 and the spirodicar-
boxylic acid. We also thank Ms. Jie Chen in this group for re-
producing the results of entries 4, 8, and 15 presented in
Table 2.
[12] For reports on the access to optically active indolines,
see: a) G. Sanz Gil, U. M. Groth, J. Am. Chem. Soc.
2000, 122, 6789; b) K.-T. Yip, M. Yang, K.-L. Law, N.-
Y. Zhu, D. Yang, J. Am. Chem. Soc. 2006, 128, 3130;
c) B. M. Trost, J. Quancard, J. Am. Chem. Soc. 2006,
128, 6314; d) A. M. Hyde, S. L. Buchwald, Angew.
Chem. 2008, 120, 183; Angew. Chem. Int. Ed. 2008, 47,
177; e) J. L. Garcꢃa Ruano, J. Alemꢄn, S. Catalꢄn, V.
Marcos, S. Monteagudo, A. Parra, C. del Pozo, S. Fus-
tero, Angew. Chem. 2008, 120, 8059; Angew. Chem. Int.
Ed. 2008, 47, 7941; f) J. Barluenga, E. Tudela, A. Bal-
lesteros, M. Tomꢄs, J. Am. Chem. Soc. 2009, 131, 2096;
g) R. Kuwano, K. Sato, T. Kurokawa, D. Karube, Y. Ito,
J. Am. Chem. Soc. 2000, 122, 7614; h) F. O. Arp, G. C.
Fu, J. Am. Chem. Soc. 2006, 128, 14264.
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