2-Methyl-6-vinylpyridine1

[1122-70-9]  · C8H9N  · 2-Methyl-6-vinylpyridine  · (MW 119.18)

(stable, masked methyl vinyl ketone equivalent; bis-annulation reagent useful for the synthesis of fused ring systems;2,3 1,5-diketone precursor4)

Physical Data: clear liquid, bp 65-70 °C/12 mmHg.

Solubility: sol all common organic solvents.

Preparative Method: prepared in a two-step procedure from 2,6-Lutidine in an overall 30% yield.5

Handling, Storage, and Precautions: store under nitrogen at rt; unpleasant odor; use in a fume hood.

Annulations.

2-Methyl-6-vinylpyridine is a stable, masked equivalent of two moles of Methyl Vinyl Ketone that has been utilized in the synthesis of steroid ring systems.2,3 In addition, 2-methyl-6-vinylpyridine derivatives have found use as a convenient synthon of 1,5-diketones.4 Alkylation of the vinylpyridine2,3,6 followed by Birch reduction of the appropriately protected substrate generates a cyclohexenone (eq 1).

The mode of cyclization of the intermediate 1,5-diketone is predictable and dependent on the substitution pattern (eq 2). Thus Birch reduction of 2-cyclohexylethyl-6-methylpyridine (1) (R = cyclohexyl) produces 100% of 3-cyclohexylethylcyclohex-2-enone (2) (R = cyclohexyl), while reduction of the corresponding 2-ethyl-6-methylpyridine (1) (R = H) affords >90% 2,3-dimethylcyclohex-2-enone (3) (R = H).4c

Other examples of heterocyclic bis-annulation reagents include 3-chloromethyl-2,4-dimethylisoxazole,7 N-benzyl-2,6-dicyanopiperidine,8 and 2,6-dimethyl-4H-pyran-4-one.9

Related Reagents.

Methyl Vinyl Ketone.


1. Kametani, T.; Nemoto, H. H 1978, 10, 349.
2. (a) Danishefsky, S.; Nagel, A. CC 1972, 373. (b) Danishefsky, S.; Cain, P.; Nagel, A. JACS 1975, 97, 380. (c) Danishefsky, S.; Cain, P. JACS 1975, 97, 5282.
3. Kutney, J. P.; Grice, P.; Piotrowska, K.; Rettig, S. J.; Szykula, J.; Trotter, J.; Chu, L. V. HCA 1983, 66, 1820.
4. (a) Danishefsky, S.; Nagel, A.; Peterson, D. CC 1972, 374. (b) Danishefsky, S.; Cain, P. JOC 1975, 40, 3606. (c) Danishefsky, S.; Zimmer, A. JOC 1976, 41, 4059.
5. Prasad, K. S. N.; Raper, R. JCS 1956, 217.
6. (a) Singerman, G.; Danishefsky, S. TL 1964, 2249. (b) Danishefsky, S.; Cavanaugh, R. JACS 1968, 90, 520.
7. Stork, G.; Danishefsky, S.; Ohashi, M. JACS 1967, 89, 5459.
8. Takahashi, K.; Asakawa, M.; Ogura, K. CL 1988, 1109.
9. Yamamoto, M.; Iwasa, S.; Takatsuki, K.; Yamada, K. JOC 1986, 51, 346.

Arthur A. Nagel

Pfizer Central Research, Groton, CT, USA



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