Michael Addition of Nitroalkanes to Dimethyl Citraconate, with DBU as Base: An Unexpected, One-Pot Synthesis of Polyfunctionalized Carbonyl Derivatives

Abstract

Michael addition of nitroalkanes to dimethyl citraconate, with DBU as base, allows the one pot formation of keto diesters. The reaction proceeds through an equilibrium form of the acceptor, followed by Michael addition of the nitroalkane and then, in situ Nef conversion.

DBU - Nef reaction - keto esters - nitroalkanes - dimethyl citraconate

References

1 Ballini R. Rinaldi A. Tetrahedron Lett.  1994,  35:  9247 

2 Ballini R. Bosica G. Tetrahedron  1995,  51:  4213 

3 Ballini R. Marcantoni E. Perella S. J. Org. Chem.  1999,  64:  2954 

4 Ballini R. Bosica G. Damiani M. Righi P. Tetrahedron  1999,  55:  13451 

5 Ballini R. Bosica G. Masè A. Petrini M. Eur. J. Org. Chem.  2000,  2927 

6 Ballini R. Bosica G. Fiorini D. Gil MV. Petrini M. Org. Lett.  2001,  3:  1265 

7 Ballini R. Bosica G. Fiorini D. Righi P. Synthesis  2002,  681 

8

PM3 semiempirical calculations by using the Gaussian 94W package showed that 9 is more stable than 6 by 2.0 kcal/mol. Gaussian 98 (Revision A.7): Frisch M. J., Trucks G. W., Schlegel H. B., Scuseria G. E., Robb M. A., Cheeseman J. R., Zakrzewski V. G., Montgomery J. A. Jr., Stratmann R. E., Burant J. C., Dapprich S., Millam J. M., Daniels A. D., Kudin K. N., Strain M. C., Farkas O., Tomasi J., Barone V., Cossi M., Cammi R., Mennucci B., Pomelli C., Adamo C., Clifford S., Ochterski J., Petersson G. A., Ayala P. Y., Cui Q., Morokuma K., Malick D. K., Rabuck A. D., Raghavachari K., Foresman J. B., Cioslowski J., Ortiz J. V., Baboul A. G., Stefanov B. B., Liu G., Liashenko A., Piskorz P., Komaromi I., Gomperts R., Martin R. L., Fox D. J., Keith T., Al-Laham M. A., Peng C. Y., Nanayakkara A., Gonzalez C., Challacombe M., Gill P. M. W., Johnson B., Chen W., Wong M. W., Andres J. L., Gonzalez C., Head-Gordon M., Replogle E. S., Pople J. A.; Gaussian 98 (Revision A.7); Gaussian, Inc.: Pittsburgh PA, 1998;

9 Recently we found that treatment of secondary nitroalkanes with DBU proceeds through the Nef conversion of the nitro groups to ketones: Ballini R. Bosica G. Fiorini D. Petrini M. Tetrahedron Lett.  2002,  43:  5233 

10 Hall N. Science  1994,  266:  32 

11a Fujimura T. Aoki S. Nakamura E. J. Org. Chem.  1991,  56:  2809 

(b) Cardillo G. Orena M. Porzi G. Sandri S. Tomasini C. J. Org. Chem.  1984,  49:  701 ; and references cited therein

11c Ravid V. Iverstein RM. Smith LR. Tetrahedron  1978,  34:  1449 

11d May WA. Peterson RS. Chang SS. J. Food Sci.  1978,  43:  1248 

11e Edwards ML. Bambury RE. Ritter HW. J. Med. Chem.  1976,  19:  330 

11f Naoshima Y. Ozawa H. Xondo H. Hayashi S. Agric. Biol. Chem.  1983,  47:  1431 

12 Harrowven DC. Poon HS. Tetrahedron Lett.  1996,  37:  4281 

13

Selected analytical data for the compounds 8h,i. 8h: IR: 3412, 1738 cm^-1; ¹H NMR (CDCl₃): δ = 1.3-1.6 (m, 6 H), 2.42 (bt, 2 H, J = 7.0 Hz), 2.56 (dd, 1 H, J = 16.6 and 6.7 Hz), 2.62 (dd, 1 H, J = 17.7 and 6.1 Hz), 2.68 (dd, 1 H, J = 16.5 and 6.4 Hz), 2.91 (dd, 1 H, J = 18.0 and 7.0 Hz), 3.2-3.3 (m, 1 H), 3.6-3.7 (m, 2 H), 3.65 (s, 3 H), 3.66 (s, 3 H); ¹³C NMR (CDCl₃): δ = 23.3, 25.2, 32.4, 35.1, 36.3, 42.7, 43.1, 51.9, 52.2, 62.5, 172.0, 174.1, 208.3; MS (EI, 70 eV)
m/z 278 (M⁺ + 4), 257, 243, 187, 170, 127 (100%), 69, 55, 41, 31. 8i: IR: 1741 cm^-1; ¹H NMR (CDCl₃): δ = 2.14 (s, 3 H), 2.56 (dd, 1 H, J = 16.8 and 6.3 Hz), 2.6-2.8 (m, 6 H), 2.96 (dd, 1 H, J = 18.6 and 6.6 Hz), 3.2-3.3 (m, 1 H), 3.65 (s, 3 H), 3.66 (s, 3 H); ¹³C NMR (CDCl₃): δ = 30.3, 35.5, 36.6, 36.8, 37.4, 43.6, 52.3, 52.7, 172.5, 174.5, 207.2, 207.4; MS (EI, 70 eV) m/z 259 (M⁺ + 1), 226, 187, 127, 99 (100%), 59, 43, 29.