J. Am. Chem. SOC. 1983, 105, 6993-6994 t-CH=CHC,H,, 69%, mp 99-102 "c). To demonstrate the utility of these transformations in natural product construction two formal total syntheses of camptothecin (7),a molecule of renewed recent interest,16J7were executed4 as in Scheme I1 in respectable yield2I through the intermediacy of the two key intermediates 5 and 6. The present work offers a uniquely versatile way to assemble annulated pyridones with extensive control of their substitution pattern,I3 by using a transition metal as a template on which to simultaneously generate three new bonds. This approach should surpass the flexibility attained by conventional Diels-Alder routes.22 Finally, we note that another catalyst reported to catalyze the formation of 2-pyridones from alkynes and isocyanates, bis(v4cyclooctadiene)nicke1,23 is unsuccessful in our systems and very likely operates through an alternative mechanism." Acknowledgment. This work was supported by the NSF (CHE 82-00049). K.P.C.V. is a Camille and Henry Dreyfus Teacher-Scholar (1978-1983). We thank Professors Buchi and Danishefsky for providing us with comparison data and Harold Helson for technical help. (16) Ihara, M.; Noguchi, K.; Ohsawa, T.; Fukumoto, K.; Kametani, T. Heterocycles 1982, 19, 1835. Miyasaka, T.; Sawada, S.; Nokata, K. Ibid. 1981, 16, 1713. Eckert, H. Angew. Chem., Int. Ed. Engl. 1981, 20, 208. (17) Wani, M. C.; Rowman, P. E.; Lindley, J. T.; Wall, M. E. J . Med. Chem. 1980, 23, 554. Shanghai No. 5 Pharm. Plant, Sci. Sin. (Engl. Trans/.) 1978, 21, 87. (18) Tang, C. S. F.; Morrow, C. J.; Rapport, H. J . Am. Chem. SOC.1975, 97, 159. (19) Volkmann, R.; Danishefsky, S.; Eggler, J.; Solomon, D. M. J . Am. Chem. SOC.1971, 93, 5576. Bradley, J. C.; Biichi, G. J . Org. Chem. 1976, 41,699. Kende, A. S.; Bentley, T. J.; Draper, R. W.; Jenkins, J. K.; Joyeux, M.; Kubo, I. Tetrahedron Lett. 1973, 1307. Quick, J. Ibid. 1977, 327. (20) Sosnovsky, G.; Krogh, J. A,; Umhoefer, S. G. Synthesis 1979, 722. (2!) For example, 5 is made by us starting from 3-carbomethoxypropanoyl chloride in 9 steps, 9% yield, superior to the Danishefsky ( 1 1 steps, 1.2%) and Quick's synthesis" (IO steps, 9%) both from 3-aminopropanal diethylacetal, and the Kende approach19 from furfural dimethylacetal ( 1 3 steps, 2.7%), but inferior to Biichi's ~ t r a t e g y from ' ~ methyl 2,2-dimethoxyethanoate (6 steps, 18%). (22) Sainte, F.; Serckx-Poncin, B.; Hesbain-Frisque, A.-M; Ghosez, L. J . Am. Chem. SOC.1982, 104, 1428. (23) Hoberg, H; Oster, B. W. J . Orgummet. Chem. 1982, 234, C35; 1983, 252, 359; Synthesis 1982, 324.
Iminium Ion and Acyliminium Ion Initiated Cyclizations of Vinylsilanes. Regiocontrolled Construction of Unsaturated Azacyclics Larry E. Overman,* Thomas C. Malone, and G. Patrick Meierl Department of Chemistry, University of California Irvine, California 9271 7 Received July 27, 1983 Vinylsilanes are rapidly becoming important terminators for cationic cyclizations.2 We have described2"Sba general stereocontrolled synthesis of alkylidene azacyclics by the intramolecular reaction of vinylsilanes with iminium ions (1 2). During the course of these studies, we became interested in whether these weakly reactive cyclization components would also participate in
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( I ) N I H Postdoctoral Fellow, 1981-1983. (2) (a) Overman, 1. E.; Bell, K. L. J . Am. Chem. SOC.1981, 103, 1851-1853. (b) Overman, L. E.; Malone, T. C. J. Org. Chem. 1982, 47, 5297-5300. (c) Burke, S. D.; Murtiashaw, C. W.; Dike, M. S.; SmithStrickland, S. M.; Saunders, J. 0. Ibid. 1981, 46, 2400-2402. (d) Trost, B. M.; Murayama, E. J . Am. Chem. SOC.1981, 103, 6529-6530. (e) Mikami, K.; Kishi, N.; Nakai, T. Tetrahedron Lett. 1983, 24,795-798. (f) Nakamura, E.; Fukuzaki, K.; Kuwajima, I. J . Chem. SOC.,Chem. Commun. 1983, 499-501.
0002-7863/83/ 1505-6993$01.50/0
6993
Scheme I
I BU'
I
IS R
14. ( Z ) R = H
It
I
R
R
I7
6
-
ring closures that are endocyclic3 with respect to the vinylsilane terminator (1 3). In this communication, we report that such R'
7I
R2
R2
SiMeS eRn' d=oSc iyMc lei 3c
exocyclic
2
-
R " a R 2
3
I
cyclizations do occur readily and provide a useful new method for the regiocontrolled assembly of unsaturated azacyclic systems. We initially explored cyclizations to form tetrahydropyridines. The starting (Z)-4-(trimethylsilyl)-3-butenamines (4)4 were prepared by aminolysis (excess amine, 25-80 "C) of readily available tosylate 5.4,5 Reactions of 4 with excess paraformaldehyde occured in refluxing acetonitrile in the presence of 0.95 equiv of camphorsulfonic acid to give 1,2,5,6-tetrahydropyridines 6-94 in excellent yields. Alternatively, a (cyanomethyl)amine6 M e , S Q
- 0-
Me3Si
RZ
7 nC3H7
kl
4 , R = NHR'
6 , R 1 = nC3H7, R 2 = H (90%)
5 , R = OTs
7 , R I = Ph, R 2 = H ( 7 5 % )
11, R= NCH~CN
b
e,
RI =
9, R 1
-@,
IO
R ~ = (H7 5 % )
CH2+0Me,
1 2 , R 1 = CH2-@OMe,
R 2 = H (92%) R 2 = n C 6 H 1 3 (45%)
13, R ' = P h , R 2 = nC6H13 ( 6 8 % )
-
could be employed and the cyclization (e.g., 11 8, 56%) accomplished by treatment with silver trifluoroacetate (1 equiv, 100 "C). The stereochemistry of the vinylsilane terminator was not critical, since the (E)-vinylsilane lO43'
