[33846-95-6]  · C11H15MoNO5  · (337.18)

(catalyst for cycloisomerizations of terminal alkynyl alcohols, and other mechanistically related transformations of terminal alkynes1)

Physical Data: for (Et3N)Mo(CO)5: lmax 393 nm; IR n (trans CO stretch) 1915 cm-1; for (Me3N)Mo(CO)5: mp 70°C2, mp 80°C;3 IR n 2072, 1941, 1921 cm-1.

Preparative Methods: (Me3N)Mo(CO)5 has been prepared by reaction of commercially available Mo(CO)6 with trimethylamine N-oxide in dichloromethane, and purified by recrystallization from a pentane solution.2 (Et3N)Mo(CO)5 is best prepared in situ by 350 nm irradiation of Mo(CO)6 in an inert solvent such as cyclohexane or diethyl ether, in the presence of triethylamine.4,5

Handling, Storage, and Precautions: (Et3N)Mo(CO)5 is generated from Mo(CO)6, which is a toxic solid compound. As the photochemical procedure for generating (Et3N)Mo(CO)5 also produces carbon monoxide, and decomposition of (Et3N)Mo(CO)5 may be reasonably expected to evolve carbon monoxide, all transformations of (Et3N)Mo(CO)5 and the Mo(CO)6 precursor should be conducted in an efficient fume hood. Mo(CO)6 is reported to be incompatible with strong oxidizing agents,6 and diethyl ether solutions of Mo(CO)6 may explode during storage.7

Cycloisomerizations of 4-Hydroxyalk-1-ynes to Dihydrofurans

(Et3N)Mo(CO)5 and (Me3N)Mo(CO)5 react with homopropargylic alcohols (4-hydroxyalk-1-ynes) to provide cycloisomeric dihydrofurans.8 Yields are somewhat lower with (Me3N)Mo(CO)5 prepared from Mo(CO)6 and trimethylamine N-oxide, so the photochemically generated (Et3N)Mo(CO)5 catalyst is currently preferred. This alkynol cycloisomerization transformation is compatible with aromatic rings, silyl ethers, and carboxylic esters and amides.9 The stereochemical integrity of chiral secondary alcohol substrates is maintained under the reaction conditions. Dihydrofuran products from alkynol cycloisomerization have been converted into several biologically important nucleosides, including cordycepin (5), the anti-AIDS compound stavudine (6),10 and puromycin aminonucleoside (9) (eq 1-3).9

(Et3N)Mo(CO)5 is not a general catalyst for cycloisomerization of 5-hydroxyalk-1-ynes, although the cyclic carbamate-containing alkynyl alcohol 10 provided a modest yield of the highly substituted dihydropyran 11 (eq 4).11 Tungsten carbonyl-catalyzed methods have subsequently been developed for high-yield cycloisomerizations of substituted 5-hydroxyalk-1-ynes to the corresponding dihydropyrans.12 The enyne ester 12 undergoes cyclization with stoichiometric (Et3N)Mo(CO)5 to provide the molybdenum oxacarbene complex 13 (eq 5).13

Cyclizations of 4-Hydroxyalk-1-ynes in the Presence of Electrophiles

(Et3N)Mo(CO)5-catalyzed cyclizations of 4-hydroxyalk-1-ynes in the presence of tributyltin triflate provide 1-(tributylstannyl)dihydrofurans in good yield, resulting from reaction of an organomolybdenum catalytic intermediate with tributyltin triflate (eq 6).14 This transformation was utilized in a synthesis of the natural product manoalide (eq 7).15

In contrast, alkynyl alcohol cyclizations in the presence of aldehydes are accompanied by carbon-carbon bond formation at C-2 of the cyclization product, and enolizable aldehydes including acetaldehyde afford the conjugated diene 18 (eq 8).

Cycloisomerization Syntheses of Furans.

Reactions of epoxyalkynes including 19 with (Et3N)Mo(CO)5 produce the corresponding furan 20 (eq 9). However, the substrate 21 affords furan 22 via a mechanism of alkynol cyclization coupled with opening of the epoxide leaving group (eq 10).16 The cyclic hemiacetal substrate 23 also provides furan 24, an intermediate in the total synthesis of salinomycin (eq 11).17

Cyclizations of Terminal Alkynes Tethered to Other Nucleophiles.

(Et3N)Mo(CO)5-promoted azacycloisomerizations of alkynes tethered to nitrogen nucleophiles have been explored. Although primary alkylamines are incompatible with the (Et3N)Mo(CO)5 catalyst and N-acetamide or N-sulfonamide substrates are unreactive, the tert-butylcarbamate derivative of 1-aminobut-3-yne 25 undergoes cycloisomerization to the corresponding cyclic enecarbamate 26 (eq 12). Similarly, ortho-aminophenylacetylene 27 undergoes cycloisomerization to indole 28 (eq 13).18

Stabilized enolates obtained from deprotonation of 1,3-diketones, b-ketoesters, or substituted malonate esters 29 undergo cyclization with stoichiometric (Et3N)Mo(CO)5 to provide substituted cyclopentenes 30 (eq 14).19

Related Reagents.

(DABCO)tungsten pentacarbonyl, (Et3N)tungsten pentacarbonyl.

1. McDonald, F. E., Chem. Eur. J. 1999, 5, 3103.
2. Koelle, U., J. Organomet. Chem. 1977, 133, 53.
3. Strohmeier, W.; Guttenberger, J. F.; Blumenthal, H.; Albert, G., Chem. Ber. 1966, 99, 3419.
4. Wrighton, M.; Hammond, G. S.; Gray, H. B., J. Am. Chem. Soc. 1971, 93, 4336.
5. Stiegman, A. E.; Stieglitz, M.; Tyler, D. R., J. Am. Chem. Soc. 1983, 105, 6032.
6. Lenga, R. E.; Votoupal, K. L., The Sigma-Aldrich Library of Regulatory and Safety Data 1993, 2, 3141.
7. Sax, N. I.; Lewis, R. J., Dangerous Properties of Industrial Materials, seventh edition; 1989, Vol. 3, p 1852.
8. McDonald, F. E.; Connolly, C. B.; Gleason, M. M.; Towne, T. B.; Treiber, K. D., J. Org. Chem. 1993, 58, 6952.
9. McDonald, F. E.; Gleason, M. M., J. Am. Chem. Soc. 1996, 118, 6648.
10. McDonald, F. E.; Gleason, M. M., Angew. Chem., Int. Ed. Engl. 1995, 34, 350.
11. McDonald, F. E.; Zhu, H. Y. H., Tetrahedron 1997, 53, 11061.
12. McDonald, F. E.; Reddy, K. S.; Díaz, Y., J. Am. Chem. Soc. 2000, 122, 4304.
13. Ohe, K.; Miki, K.; Yokoi, T.; Nishino, F.; Uemura, S., Organometallics 2000, 19, 5525.
14. McDonald, F. E.; Schultz, C. C.; Chatterjee, A. K., Organometallics 1995, 14, 3628.
15. Pommier, A.; Kocienski, P. J., Chem. Commun. 1997, 1139.
16. McDonald, F. E.; Schultz, C. C., J. Am. Chem. Soc. 1994, 116, 9363.
17. Kocienski, P. J.; Brown, R. C. D.; Pommier, A.; Proctor, M.; Schmidt, B., J. Chem. Soc., Perkin Trans. 1 1998, 9.
18. McDonald, F. E.; Chatterjee, A. K., Tetrahedron Lett. 1997, 38, 7687.
19. McDonald, F. E.; Olson, T. C., Tetrahedron Lett. 1997, 38, 7691.

Frank E. McDonald

Emory University, Atlanta, GA, USA

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