R. Grigg et al. / Tetrahedron 65 (2009) 849–854
853
Prepared by the general procedure from tert-butyl cyanoacetate
(0.141 g, 1.0 mmol), KOH (0.011 g, 0.20 mmol), [IrCp Cl2]2 (0.020 g,
(OCH3), 37.69 (CH), 32.30 (CH2), 31.59 (CH2), 27.80 (3ꢁCH3); nmax
*
(cmꢂ1) (film): 2936, 2248 (CN), 1738 (CO), 1517, 1155, 1028.
0.025 mmol) and 2-methoxybenzyl alcohol (0.207 g, 1.5 mmol)
with heating at 100 ꢀC for 8 h. Chromatography, eluting with 7:1 v/v
hexane and ethyl acetate, gave the product (0.225 g, 86%) as a col-
ourless oil; dH (500 MHz, CDCl3): 7.27 (apparent t, 1H, J 7.7 Hz, H4),
7.19 (d, 1H, J 7.7 Hz, H6), 6.91 (apparent t, 1H, J 8.1 Hz, H5), 6.87 (d,
1H, J 8.1 Hz, H3), 3.85 (s, 3H, OCH3), 3.84 (dd, 1H, J 6.8, 9.0 Hz, CH),
3.30 (dd, 1H, 6.8, 13.3 Hz, CHH), 3.09 (dd, 1H, J 9.0, 13.3 Hz, CHH),
1.44 (s, 9H, 3ꢁCH3); dC (75 MHz, CDCl3): 165.36 (CO), 157.87 (ArC),
131.60 (ArCH), 129.53 (ArCH), 124.27 (ArC), 121.04 (ArCH), 117.43
(CN), 110.72 (ArCH), 84.18 (C), 55.67 (OCH3), 38.64 (CH), 32.05
(CH2), 28.16 (3ꢁCH3); nmax (cmꢂ1) (film): 2979, 1737, 1602, 1495,
1464, 1369, 1246, 1149; HRMS [ESþ] found MþNa 284.1254.
C15H19NO3Na requires 284.1257.
4.2.11. tert-Butyl 2-cyano-3-(thiophen-2-yl)propanoate (12)
S
O
CN
O
Prepared by the general procedure from tert-butyl cyanoacetate
(0.141 g, 1.0 mmol), KOH (0.011 g, 0.20 mmol), [IrCp Cl2]2 (0.020 g,
*
0.025 mmol) and 2-thiophene methanol (0.117 g, 1.5 mmol) with
heating at 100 ꢀC for 4 h. Chromatography, eluting with 4:1 v/v
hexane and ethyl acetate, gave the product (0.160 g, 68%) as a
colourless oil; dH (500 MHz, CDCl3): 7.22 (dd, 1H, J 1.3, 4.8 Hz, H5),
7.01–6.95 (m, 2H, H3 and H4), 3.67 (dd, 1H, J 6.0, 7.3 Hz, CH), 3.45
(dd, 1H, J 6.0, 15.0 Hz, CHH), 3.41 (dd, 1H, J 7.3, 15.0 Hz, CHH), 1.47
(s, 9H, 3ꢁCH3); dC (75 MHz, CDCl3): 163.97 (CO), 136.99 (ArC),
127.22 (ArCH), 127.18 (ArCH), 125.23 (ArCH), 116.32 (CN), 84.56
(C), 40.72 (CH), 29.96 (CH2), 27.75 (3ꢁCH3); nmax (cmꢂ1) (film):
2980, 2929, 1737 (CO), 1435, 1370, 1257, 1152, 836; HRMS [ESþ]
found MþNa 260.0723. C12H15NNaO2S requires 260.0716.
4.2.9. tert-Butyl 3-(benzo[d][1,3]dioxol-5-yl)-2-cyano-
propanoate (10)
O
O
O
CN
O
4.2.12. tert-Butyl 2-cyano-3-(furan-2-yl)propanoate (13)
Prepared by the general procedure from tert-butyl cyanoacetate
(0.141 g, 1.0 mmol), KOH (0.011 g, 0.20 mmol), [IrCp Cl2]2 (0.020 g,
*
O
0.025 mmol) and 3,4-methylenedioxy benzyl alcohol (0.228 g,
1.5 mmol) with heating at 100 ꢀC for 4 h. Chromatography, eluting
with 4:1 v/v hexane and ethyl acetate, gave the product (0.165 g,
60%) as a colourless oil; dH (500 MHz, CDCl3): 6.78–6.72 (m, 3H,
H2,H5 and H6), 5.95 (s, 2H, OCH2O), 3.57 (dd,1H, J 6.0, 8.1 Hz, CH), 3.15
(dd, 1H, J 6.0, 13.7 Hz, CHH), 3.08 (dd, 1H, J 8.1, 13.7 Hz, CHH), 1.47 (s,
9H, C(CH3)3); dC (75 MHz, CDCl3): 164.40 (CO), 147.89 (ArC), 147.12
(ArC),129.08(ArC),122.43(ArCH),116.53(CN),109.39(ArCH),108.49
(ArCH), 101.14 (CH2), 84.30 (C), 40.82 (CH), 35.53 (CH2), 27.78
(3ꢁCH3); nmax (cmꢂ1) (film): 2981,1738,1504,1491,1445,1370,1249,
1151; HRMS [ESþ] found Mþ1 276.1220. C15H17NO4 requires
276.1230.
O
CN
O
Prepared by the general procedure from tert-butyl cyanoacetate
(0.141 g, 1.0 mmol), KOH (0.011 g, 0.20 mmol), [IrCp Cl2]2 (0.020 g,
*
0.025 mmol) and furfuryl alcohol (0.162 g, 1.5 mmol) with heating
at 100 ꢀC for 24 h. Chromatography, eluting with 4:1 v/v hexane
and ethyl acetate, gave the product (0.115 g, 52%) as a colourless oil;
dH (500 MHz, CDCl3): 7.36 (d, 1H, J 1.3 Hz, H5), 6.32 (dd, 1H, J
1.3, 3.4 Hz, H4), 6.24 (d, 1H, J 3.4 Hz, H3), 3.73 (dd, 1H, J 6.4, 7.7 Hz,
CH), 3.28 (dd, 1H, J 6.4, 15.2 Hz, CHH), 3.23 (dd, 1H, J 7.7, 15.2 Hz,
CHH), 1.48 (s, 9H, 3ꢁCH3); dC (75 MHz, CDCl3): 164.03 (CO), 149.17
(ArC), 142.39 (ArCH), 116.24 (CN), 110.56 (ArCH), 108.28 (ArCH),
4.2.10. tert-Butyl 2-cyano-4-(3,4-dimethoxyphenyl)-butanoate (11)
OMe
OMe
84.41 (C), 37.99 (CH), 28.57 (CH2), 27.72 (3ꢁCH3); nmax (cmꢂ1
)
(film): 2982, 1740, 1371, 1282, 1254, 1153, 1015, 839; HRMS [ESþ]
found Mþ1 222.1123. C12H16NO3 requires 222.1125.
Acknowledgements
O
CN
We thank Leeds University, Pfizer and Johnson Matthey for
support.
O
Prepared by the general procedure from tert-butyl cyanoacetate
References and notes
(0.141 g, 1.0 mmol), KOH (0.011 g, 0.20 mmol), [IrCp Cl2]2 (0.020 g,
*
0.025 mmol) and 3,4-dimethoxy phenethyl alcohol (0.270 g,
1.5 mmol) with heating at 100 ꢀC for 4 h. Chromatography, eluting
with 4:1 v/v hexane and ethyl acetate, followed by crystallisation of
the residue from DCM and hexane gave the product (0.161 g, 53%)
as colourless prisms; mp 62–63 ꢀC. (Found: C, 66.85; H, 7.65; N,
4.80. C17H23NO4 requires: C, 66.86; H, 7.59; N, 4.59%.) dH (500 MHz,
CDCl3): 6.82 (d, 1H, J 8.1 Hz, H5), 6.75 (dd, 1H, J 1.7, 8.1 Hz, H6), 6.72
(d, 1H, J 1.7 Hz, H2), 3.88 (s, 3H, OCH3), 3.86 (s, 3H, OCH3), 3.34 (dd,
1H, J 6.8, 8.1 Hz, CH), 2.86–2.80 (m, 1H, CHH), 2.76–2.70 (m, 1H,
CHH), 2.22–2.17 (m, 2H, ArCH2), 1.50 (s, 9H, 3ꢁCH3); dC (75 MHz,
CDCl3): 165.00 (CO), 149.07 (ArC), 147.78 (ArC), 131.72 (ArC), 120.46
(ArCH), 116.82 (CN), 111.67 (ArCH), 84.09 (C), 55.93 (OCH3), 55.88
1. (a) Schreiber, S. L. Science 2000, 287, 1964–1969; (b) Spring, D. R. Org. Biomol.
Chem. 2003, 1, 3867–3870; (c) Itami, K.; Yoshida, J. I. Chem.dEur. J. 2006, 12,
3966–3974.
2. Grigg, R.; Mitchell, T. R. B.; Sutthivaiyakit, S.; Tongpenyai, N. Tetrahedron Lett.
1981, 22, 4107–4711.
3. (a) Motokura, K.; Nishimura, D.; Mori, K.; Mizugaki, T.; Ebitani, K.; Kaneda, K.
J. Am. Chem. Soc. 2004, 126, 5662–5663; (b) Lofberg, C.; Grigg, R.; Whittaker,
M. A.; Keep, A.; Derrick, A. J. Org. Chem. 2006, 71, 8023–8027.
4. Lofberg, C.; Grigg, R.; Keep, A.; Derrick, A.; Sridharan, V.; Kilner, C. Chem.
Commun. 2006, 5000–5002.
5. Whitney, S.; Grigg, R.; Derrick, A.; Keep, A. Org. Lett. 2007, 9, 3299–3302.
6. Cho, C. S.; Kim, B. T.; Kim, T. J.; Shim, S. C. J. Org. Chem. 2001, 6, 9020–9022.
7. Cho, C. S.; Kim, T. J.; Shim, S. C. Tetrahedron Lett. 2002, 43, 7987–7990.
8. (a) Martinez, R.; Brand, G. J.; Ramon, D. J.; Yus, M. Tetrahedron Lett. 2005, 46,
3683–3686; (b) Martinez, R.; Ramon, D. J.; Yus, M. Tetrahedron 2006, 62,