2950
A. J. Clarke, D. A. Hunt / Tetrahedron Letters 50 (2009) 2949–2951
OR
NH
CO2-t-Bu
O
OR
OR
CO2-t-Bu
Br
O
O
n-BuLi/-78 oC/THF
O
NO2
Bz
O
O
O
O2N
Bz
O
O
O
4
5
O
O
O
O
7
O
6
Scheme 2.
H
CN
N H
CN
Li
CN 1. n-BuLi/-100 oC/THF
O
-100 oC
rt
N
NO2
NO2
O
NO2
Br
R3
R2
R3
R2
2.
R1
R3
R3
8
R2
R1
R2
9
R1
12
R1
10
11
Scheme 3.
CN
Acknowledgments
NO2
Li
We wish to thank The College of New Jersey for their generous
support of this work.
OCH3
References and notes
10d
1. (a) Parham, W. E.; Bradsher, C. K. Acc. Chem. Res. 1982, 15, 300–305; (b)
Clayden, J. Organolithiums: Selectivity for Synthesis; Pergamon: New York, 2002.
Chapter 7, pp. 282–329; (c) Sotomayor, N.; Lete, E. Curr. Org. Chem. 2003, 7,
275–300; (d) El Sheikh, S.; Schmalz, H.-Z. Curr. Opin. Drug Discovery Dev. 2004,
7, 882–895.
Figure 1.
2. Parham, W. E.; Egberg, D. C.; Sayed, Y. A.; Thraikill, R. W.; Keyser, G. E.; Neu, M.;
Montgomery, W. C.; Jones, L. D. J. Org. Chem. 1976, 41, 2628–2633.
3. Bradsher, C. K.; Hunt, D. A. J. Org. Chem. 1980, 45, 4248–4250.
Table 1
H
4. Parham, W. E.; Jones, L. D. J. Org. Chem. 1976, 41, 1187–1191.
N H
5. (a) Bradsher, C. K.; Hunt, D. A. J. Org. Chem. 1981, 46, 327–330; (b) Campbell, J.
B.; Dedinas, R. F.; Trumbower-Walsh, S. A. J. Org. Chem. 1996, 61, 6205.
6. Parham, W. E.; Jones, L. D. J. Org. Chem. 1976, 41, 2704–2706.
7. Parham, W. E.; Piccirilli, R. M. J. Org. Chem. 1976, 41, 1268–1269.
8. (a) Seebach, D.; Leitz, H. F. Agnew. Chem., Intl. Ed. Engl. 1969, 8, 983; (b) Knochel,
P.; Seebach, D. Tetrahedron Lett. 1981, 22, 3223–3226; (c) Yao, C-F.; Kao, K-H.;
Liu, J-T.; Chu, C.-M.; Wang, Y.; Chen, W.-C.; Lin, Y.-M.; Yan, M.-C.; Liu, J.-Y.;
Chuang, M.-C.; Shiue, J.-L. Tetrahedron 1998, 54, 791–822; (d) Valleix, F.; Nagai,
K.; Soeta, T.; Kuriyama, M.; Yamada, K.; Tomioka, K. Tetrahedron 2005, 61,
7420–7424.
CN
O
N
NO2
O
R3
R2
R3
R2
11
R1
12
R1
9. For examples, see: (a) Michaelides, M. R.; Hong, Y.; DiDomenico, S.; Bayburt, E.
K.; Asin, K. E.; Britton, D. R.; Lin, C. W.; Shiosaki, K. J. Med. Chem. 1997, 40, 1585–
1599; (b) Yasuhara, T.; Nishimura, K.; Yamashita, M.; Fukuyama, N.; Yamada,
K.; Muraoka, O.; Tomioka, K. Org. Lett. 2003, 5, 1123–1126.
Compound
R1
H
R2
R3
Yield (%) 11
Yield (%) 12
10. Paulsen, H.; Stubbe, MK. Tetrahedron Lett. 1982, 23, 3171–3174.
11. General procedure illustrated by the preparation of 11a: To a solution of 2-
bromobenzonitrile (1.00 g; 5.49 mmol) in dry THF (25 mL) under N2 at
À100 °C, 1.1 equiv of n-butyllithium (3.92 mL; 1.4 M in hexane; 5.49 mmol)
was added at such a rate that a strong exotherm was not produced. After
stirring for 30 min at À95 to À100 °C, a solution of the nitrostyrene 9a (.819 g;
5.49 mmol in 5 mL THF) was added in the same fashion. Upon completion of
the addition, the reaction was maintained at À100 °C for 30 min, then allowed
to warm to room temperature and stirred overnight. The mixture was then
poured into water and extracted with CH2Cl2 (3 Â 35 mL). The combined
organics were dried (MgSO4), filtered, and concentrated. The crude product
was purified by recrystallization from EtOAc to afford 2-nitro-1-phenyl-1H-
inden-3-amine (11a) as a pale yellow amorphous solid, yield = 0.840 mg (61%);
9a
9b
9c
9d
9e
9f
H
H
OCH3
H
H
C2H5
H
H
H
H
H
61
52
52
39
56
54
OCH3
H
H
H
H
H
OCH3
CH3
H
CH3
OCH3
19
9e
9d
46
41
H
11a–d reveal two –NH protons which are non-equivalent, presum-
ably due to intramolecular hydrogen bonding of the enamino pro-
tons with the adjacent nitro group.13 Future work will address the
scope and limitations of Michael addition chemistry of b-nitrosty-
renes with other Parham substrates and applications to total
synthesis.
mp 211–215 °C (dec); IR: 3360, 3128, 1649, 1459, 1376 cm-1 1H NMR (DMSO-
;
d6, 300 MHz): d 5.18 s, 1, benzylic CH), 7.19–7.34 m, 6, ArH), 7.49–7.54 (m, 2,
ArH), 8.10–8.11 (m, 1, ArH), 8.44 (br s, 1, NH), 8.72 (br s, 1, NH); 13C NMR
(DMSO-d6, 75 MHz) d 51.00, 122.18, 125.34, 126.91, 127.56, 127.90, 128.58,
132.06, 140.03, 205.44. Fnal. Calcd for C15H12N2O2 1:8 H2O:C, 70.80; H, 4.82; N,
11.01. Found: C, 70.72; H, 4.58; N, 10.64.