ORGANIC LETTERS
Initiator-Dependent Chemoselective Addition of THF Radical to Aldehyde and Aldimine and Its Application to a Three-Component Reaction
2003 Vol. 5, No. 10 1797-1799
Ken-ichi Yamada, Yasutomo Yamamoto, and Kiyoshi Tomioka* Graduate School of Pharmaceutical Sciences, Kyoto UniVersity, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
[email protected] Received March 19, 2003
ABSTRACT
The product distribution of the three-component reaction of aldehydes, arylamines, and THF was dependent on a radical initiator, preferentially giving the corresponding THF adducts of imines with dimethylzinc and adducts of aldehyde with triethylborane.
Chemoselectivity has been one of the goals of organic chemistry. Especially differentiation of CdO and CdN double bonds as nucleophilic targets has been the topic of recent allylation1 and Mannich-type reactions.2 However, to the best of our knowledge, there has been no report on such differentiation for radical reactions.3 We describe herein that a THF radical4 undergoes chemoselective addition to aldehydes and aldimines depending on the choice of radicalgenerating agents, dimethylzinc and triethylborane. The chemoselectivity was well demonstrated in the threecomponent reaction of aldehydes, amines, and THF. (1) (a) Akiyama, T.; Iwai, J.; Onuma, Y.; Kagoshima, H. Chem. Commun. 1999, 2191-2192. (b) Akiyama, T.; Iwai, J. Synlett 1998, 273-274. (c) Nakamura, H.; Iwama, H.; Yamamoto, Y. J. Am. Chem. Soc. 1996, 118, 6641-6647. (d) Nakamura, H.; Iwama, H.; Yamamoto, Y. J. Chem. Soc., Chem. Commun. 1996, 1459-1460. (2) (a) Kobayashi, S.; Busujima, T.; Nagayama, S. Chem. Eur. J. 2000, 6, 3491-3494. (b) Shimizu, M.; Itohara, S. Synlett 2000, 1828-1830. (c) Tanaka, N.; Masaki, Y. Synlett 2000, 406-408. (d) Akiyama, T.; Takaya, J.; Kagoshima, H. Chem. Lett. 1999, 947-948. (e) Kobayashi, S.; Nagayama, S. J. Am. Chem. Soc. 1997, 119, 10049-10053. (f) Kobayashi, S.; Nagayama, S. J. Org. Chem. 1997, 62, 232-233. (3) For initiator-dependent chemoselective radical addition to CdO and CdC double bonds, see: Devin, P.; Fensterbank, L.; Malacria, M. Tetrahedron Lett. 1999, 40, 5511-5514. 10.1021/ol034473x CCC: $25.00 Published on Web 04/10/2003
© 2003 American Chemical Society
We have recently reported radical addition reaction of ethers with aldimines, in which methyl radicals, generated from dimethylzinc as an initiator and molecular oxygen, abstract an R-hydrogen of ethers to generate ether radicals, (4) For the reaction of an ether radical, see: (a) Yoshimitsu, T.; Arano, Y.; Nagaoka, H. J. Org. Chem. 2003, 68, 625-627. (b) Hirano, K.; Sakaguchi, S.; Ishii, Y. Tetrahedron Lett. 2002, 43, 3617-3620. (c) Mosca, R.; Fagnoni, M.; Mella, M.; Albini, A. Tetrahedron 2001, 57, 1031910328. (d) Kim, S.; Kim, N.; Chung, W.-J.; Cho, C. H. Synlett 2001, 937940. (e) Hirano, K.; Iwahama, T.; Sakaguchi, S.; Ishii, Y. Chem. Commun. 2000, 2457-2458. (f) Iwahama, T.; Sakaguchi, S.; Ishii, Y. Chem. Commun. 2000, 613-615. (g) Yoshimitsu, T.; Tsunoda, M.; Nagaoka, H. Chem. Commun. 1999, 1745-1746. (h) Inoue, A.; Shinokubo, H.; Oshima, K. Synlett 1999, 1582-1584. (i) Alves, M. J.; Gilchrist, T. L.; Sousa, J. H. J. Chem. Soc., Perkin Trans. 1 1999, 1305-1310. (j) Xiang, J.; Evarts, J.; Rivkin, A.; Curran, D. P.; Fuchs, P. L. Tetrahedron Lett. 1998, 39, 41634166. (k) Xiang, J.; Jiang, W.; Fuchs, P. L. Tetrahedron Lett. 1997, 38, 6635-6638. (l) Xiang, J.; Jiang, W.; Gong, J.; Fuchs, P. L. J. Am. Chem. Soc. 1997, 119, 4123-4129. (m) Xiang, J.; Fuchs, P. L. J. Am. Chem. Soc. 1996, 118, 11986-11987. (n) Gong, J.; Fuchs, P. L. J. Am. Chem. Soc. 1996, 118, 4486-4487. (o) Clark, A. J.; Rooke, S.; Sparey, T. J.; Taylor, P. C. Tetrahedron Lett. 1996, 37, 909-912. (p) Ishida, A.; Sugita, D.; Itoh, Y.; Takamuku, S. J. Am. Chem. Soc. 1995, 117, 11687-11694. (q) Jung, J. C.; Choi, H. C.; Kim, Y. H. Tetrahedron Lett. 1993, 34, 3581-3584. (r) Fontana, F.; Minisci, F.; Yan, Y. M.; Zhao, L. Tetrahedron Lett. 1993, 34, 2517-2520. (s) Matthews, D. P.; McCarthy, J. R. J. Org. Chem. 1990, 55, 2973-2975. (t) Gevorgyan, V.; Priede, E.; Liepins, E.; Gavars, M.; Lukevics, E. J. Organomet. Chem. 1990, 393, 333-338. (u) Russell, G.
consequently giving the ether adducts of aldimines in high yields.5-7 For example, the reaction of benzaldehyde N-4methoxyphenylimine (N-PMP-imine) 1 with THF was conducted in the presence of 6 equiv of dimethylzinc under constant air bubbling (10 mL/h), producing THF adduct 3a in 83% yield after 5 h at room temperature (Table 1, entry
The initiator-dependent chemoselectivity was more highlighted by the reaction of imino-aldehyde 5 having both carbonyl and imino groups (Scheme 1). Under the dimeth-
Scheme 1. Reaction of THF with Imino-aldehyde 5
Table 1. Initiator-Dependent Chemoselective Addition of THF Radical to Benzaldehyde PMP-imine 1 and Benzaldehyde 2a
entry
1/2a
initiator (equiv)
t (h)
product
yield (%)
1 2 3 4
1 1 2a 2a
Me2Zn (6) Et3B (12) Me2Zn (12) Et3B (12)
5 18 120 6
3a 3aa 4 4
83 63
