4-Iodo-2-trimethylstannyl-1-butene1

[99474-77-8]  · C7H15ISn  · 4-Iodo-2-trimethylstannyl-1-butene  · (MW 344.83)

(cyclopentane annulation;2,3 intramolecular Stille coupling;4 bifunctional reagent5-7)

Alternate Name: (3-iodo-1-methylenepropyl)trimethylstannane.

Physical Data: bp 50-55 °C/0.1 mmHg.8

Analysis of Reagent Purity: 1H NMR.8

Preparative Methods: by addition of trimethylstannylcuprate to 1-butyn-4-ol9,10 followed by a Mitsunobu reaction,11 or via the tosylate of 2-trimethylstannyl-1-buten-4-ol (NaI, DMF).8

Purification: by distillation.8

Handling, Storage, and Precautions: organostannanes should be considered as toxic compounds.12 This reagent should be handled in a well ventilated fume hood and gloves should be worn.

Methylene Cyclopentane Annulations.

Alkylation-Intramolecular Stille Coupling.

Bicyclic dienes have been prepared by alkylation of the N,N-dimethylhydrazone of a cyclohexanone with 4-iodo-2-trimethylstannyl-1-butene, followed by the cleavage of the hydrazone, formation of the enol triflate and palladium-catalyzed Stille coupling (eq 1) (see also 5-Chloro-2-trimethylstannyl-1-pentene).8,13

Alkylation-Vinyllithium Addition.

Treatment of the stannane derived from the alkylation of cyclohexanone with 4-iodo-2-trimethylstannyl-1-butene (see above) with Iodine affords the vinyl iodide. Treatment of this intermediate with n-Butyllithium affords an allylic, angular hydroxy annulation product (eq 2).14

This annulation sequence provides the complimentary regioisomer to that obtained by a vinylcuprate-intramolecular alkylation sequence.

Radical Annulation.

Addition of Tri-n-butylstannane to 4-iodo-2-trimethylstannyl-1-butene in the presence of N-Phenylmaleimide affords the bicyclic imide in 59% yield (eq 3). This reaction failed with methyl acrylate and phenyl vinyl sulfone.12

However, 1-t-butyldimethylsilyl-4-iodo-2-trimethylstannyl-1-butene undergoes an analogous reaction with acrylonitrile, methyl acrylate, and methyl vinyl ketone.11

Miscellaneous Related Reagents.

See also 4-Chloro-2-trimethylstannyl-1-butene, 4-Iodo-2-trimethylgermyl-1-butene, 5-Chloro-2-trimethylstannyl-1-pentene, and (Z)-5-Chloro-3-trimethylstannyl-2-pentene.

A number of homologs of the title reagent have been prepared, differing in chain length and o-substitution (eq 4).9 These have been used as methylenecyclopentane annulation reagents via the alkylation-intramolecular Stille coupling methodology (see above).8

A number of (E)- and (Z)-6-iodo-3-trimethylstannyl-2-hexenoates and related bifunctional reagents (1,2) have been prepared and used as cyclohexane annulation reagents through alkylation and intramolecular Stille coupling (eq 5).15,16

One of these reagents [(E)-1-(t-butyldimethylsiloxy)-6-iodo-3-trimethylstannyl-2-hexene] has been used in the synthesis of (±)-8,15-diisocyano-11(20)-amphilectene (eq 6).17

An annulation sequence using (Z)-1-bromo-4-methyl-3-trimethylstannyl-2-pentene has led to the synthesis of (±)-(14S)-dolasta-1(15),7,9-trien-14-ol and (±)-amijitrienol (eq 7).18-20

Another route to the synthesis of conjugated dienes has been accomplished using a Copper(I) Chloride-mediated intramolecular coupling strategy.21 This has been used to couple vinylstannanes and vinyl iodides in the absence of Pd0 catalysts (eq 8 and Table 1). In only one case (entry 4), the reaction was not stereospecific. At 60 °C, a 13:1 mixture of (2E,3E) and (2Z,3E) isomers was obtained (See footnote to Table 1). Running the reaction at 25 °C afforded a 30:1 mixture of products. It was noted that the Pd0 mediated coupling of this substrate was not stereospecific and in fact the copper-catalyzed reaction was superior.21

A general cyclopentane annulation sequence was developed using a vinylstannane that is embedded in a preexisting cycloalkene (eq 9). Initial attempts to extend this methodology to cyclohexane and cyclohexane annulations were accomplished only in low yield (12% and 35%, respectively).22

It was found subsequently that substitution of a pendent o-bromo functionality allows cyclization to both five- and seven-membered rings (eqs 10 and 11).23

This methodology was used in the synthesis of (±)-chiloscyphone and (±)-6-epi-chiloscyphone (eq 12).23

An entry into the preparation of [3.2.1]cycloheptenols utilizes vinylstannane-o-oxo compounds. Treatment of vinylstannanes (eq 13) with n-butyllithium affords the cyclopentenols in good yield.24 The starting stannanes were prepared by stannylcupration of Acetylene and cyclohexenone.25

Cyclobutenes can be synthesized using a variation of this methodology. Treatment of the o-p-toluenesulfonate-vinylstannanne with BuLi effects a tin-lithium exchange and ring closure (eqs 14 and 15).24 Preparation of the substrate is accomplished by stannylcupration of Allene,26,27 acetylene, or phenylacetylene25 followed by treatment with Ethylene Oxide, and conversion to the tosylate.24

A disubstituted stannane, (E)-1,4-di(t-butyldimethylsiloxy)-2-trimethylstannyl-2-butene, has been used as an isocoumarin annulation reagent. This was accomplished by palladium-catalyzed coupling of this reagent with methyl 2-iodo-4-methylbenzoate followed by acid-catalyzed deprotection/cyclization (eq 16). This was a key sequence in the synthesis of lacramin A.28


1. Piers, E. PAC 1988, 60, 107.
2. Mehta, G.; Karra, S. R. TL 1991, 32, 3215.
3. Panek, J. S.; Jain, N. F. JOC 1993, 58, 2345.
4. Stille, J. K.; Tanaka, M. JACS 1987, 109, 3785.
5. De Lombaert, S.; Nemery, I.; Roekens, B.; Carretero, J. C.; Kimmel, T.; Ghosez, L. TL 1986, 27, 5099.
6. Knapp, S.; O'Connor, U.; Mobilio, D. TL 1980, 21, 4557.
7. Trost, B. M. AG(E) 1986, 25, 1.
8. Piers, E.; Friesen, R. W.; Keay, B. A. T 1991, 47, 4555.
9. Piers, E.; Chong, J. M. CC 1983, 934.
10. Piers, E.; Chong, J. M. CJC 1988, 66, 1425.
11. Curran, D. P.; van Elburg, P. A. TL 1989, 30, 2501.
12. Neumann, W. P. The Organic Chemistry of Tin; Interscience: New York, 1970; pp 230-237.
13. Piers, E.; Friesen, R. W.; Keay, B. A. CC 1985, 809.
14. Piers, E.; Marais, P. C. TL 1988, 29, 4053.
15. Piers, E.; Friesen, R. W.; Rettig, S. J. CJC 1992, 70, 1385.
16. Piers, E.; Friesen, R. W. CJC 1987, 65, 1681.
17. Piers, E.; Llinas-Brunet, M. JOC 1989, 54, 1483. See also: Piers, E.; Llinas-Brunet, M.; Oballa, R. M. CJC 1993, 71, 1484.
18. Piers, E.; Friesen, R. W. CC 1988, 125.
19. Piers, E.; Friesen, R. W. CJC 1992, 70, 1204.
20. Piers, E.; Friesen, R. W. JOC 1986, 51, 3405.
21. Piers, E.; Wong, T. JOC 1993, 58, 3609.
22. Piers, E.; Tse, H. L. A. TL 1984, 25, 3155.
23. Piers, E.; Tse, H. L. A. CJC 1993, 71, 983.
24. Barbero, A.; Cuadrado, P.; González, A. M.; Pulido, F. J.; Rubio, R.; Fleming, I. TL 1992, 33, 5841.
25. Barbero, A.; Cuadrado, P.; Fleming, I.; González, A. M.; Pulido, F. J. CC 1992, 351.
26. Barbero, A.; Cuadrado, P.; Fleming, I.; González, A. M.; Pulido, F. J. JCS(P1) 1992, 327.
27. Fleming, I.; Rowley, M.; Cuadrado, P.; González-Nogal, A. M.; Pulido, F. J. T 1989, 45, 413.
28. Takle, A.; Kocienski, P. T 1990, 46, 4503.

Joseph S. Warmus

Parke-Davis Pharmaceuticals, Ann Arbor, MI, USA



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