[594-27-4]  · C4H12Sn  · Tetramethylstannane  · (MW 178.87)

(weak nucleophile which reacts with Brønsted and Lewis acids;2 source of trimethyltin halides;3 commonly used in Stille coupling4)

Alternate Name: tetramethyltin.

Physical Data: bp 74-75 °C/760 mmHg; mp -55 °C; d 1.315 g cm-3.

Solubility: sol common organic solvents; insol H2O.

Form Supplied in: widely available as a neat liquid.

Preparative Methods: synthesized by the reaction of methylmagnesium iodide with SnCl4 in Et2O or THF.5 Use of higher boiling and/or less Lewis basic solvents, such as toluene or Bu2O, lessens the need for Vigreux distillation of the product.6

Analysis of Reagent Purity: shows one peak in the GC. 1H NMR (d 0.1, JH-117Sn 54.0 Hz, JH-119Sn 51.0 Hz), 13C NMR (d -9.5), and 119Sn NMR (Me4Sn is the common standard) can also be informative.

Purification: commercial tetramethyltin is typically obtained as a colorless oil and is used without further purification. Tetramethyltin is a good solvent for silicone grease;6b contamination should be avoided.

Handling, Storage, and Precautions: is an air and water stable oil. Tetramethyltin has a high vapor pressure and containers should be well sealed before storage. Organostannanes are toxic and should only be used in a well ventilated hood. All glassware should be rinsed in a KOH/EtOH bath during cleaning.

Palladium-Mediated Cross-Coupling Reactions (Stille Coupling and Related Reactions).

Tetramethyltin acts as a nucleophile in palladium-mediated cross coupling with electrophiles.4 The coupling is general for halides with sp or sp2 centers at or adjacent to the electrophilic center. Aryl and heteroaryl halides (eq 1),7-9 acid chlorides (eq 2),10 imidoyl chlorides (eq 3),11 and some b-ketovinyl iodides (eq 4)12 have been shown to couple with tetramethyltin. Selectivity for substitution of aryl iodides over aryl chlorides is normally observed.13 The reaction has been found to be of particular use for the alkylation of the base moiety of nucleosides (eq 5).14 A variety of Pd0 and PdII catalysts may be used to mediate the cross coupling. Variation of the stabilizing ligand from PPh3 to (2-furyl)3P (PFu3) or AsPh3 appears to have little effect on the rate of the reaction.8 Reactions run at or above the boiling point of tetramethyltin often require use of a sealed flask. Workup is facilitated because the trimethyltin halide byproduct is water soluble.

Vinyl and aryl triflates (eq 6) have also proven to be valuable electrophiles in palladium-mediated cross coupling with tetramethyltin.15,16 An excess of Lithium Chloride is typically required for the successful coupling. The reaction has found particular value in the synthesis of cephalosporin analogs (eq 7).17 Palladium catalysts also mediate the cross coupling of tetramethyltin with arylboronic acids,18 arenediazonium salts,19 and arylthallium compounds.20

When conducted under 1-3 atm of carbon monoxide, cross coupling of tetramethyltin with aryl iodides,21 aryl triflates,22 and vinyl triflates (eq 8)23 affords the corresponding methyl ketone. LiCl is typically not required for the reaction to proceed. Occasionally, carbonylative coupling is accelerated by the addition of 1 equiv of anhydrous Zinc Chloride, presumably due to transmetalation to a methylzinc complex. Dicarbonylbis(triphenylphosphine)nickel(0), a more robust catalyst, has also been reported to mediate a carbonylative coupling.24

Reaction with Brønsted and Lewis Acids.

Tetramethyltin reacts with Brønsted and Lewis acids through either homolytic or heterolytic pathways to cleave a methyl-tin bond. Though reaction of Mercury(II) Chloride with tetramethyltin has been used to generate Chlorotrimethylstannane and dichlorodimethylstannane,25 disproportionation is a better route to these compounds. Direct nucleophilic reaction of tetramethyltin with Lewis acids has been effectively utilized to methylate haloboranes (eq 9),26 thionyl chloride,27 and antimony halides.28


Disproportionation of tetramethyltin with Tin(IV) Chloride in the absence of solvent provides a simple, quantitative, and relatively inexpensive route to chlorotrimethylstannane.3

Related Reagents.

Tungsten(VI) Chloride-Tetramethylstannane.

1. (a) Pereyre, M.; Quintard, J.-P.; Rahm, A. Tin in Organic Synthesis; Butterworths: London, 1987. (b) Davies, A. G.; Smith, P. J. In Comprehensive Organometallic Chemistry; Wilkinson, G.; Stone, F. G. A.; Abel, E. W., Eds.; Pergamon: Oxford, 1982; Chapter 11. (c) Ingham, R. K.; Rosenberg, S. D.; Gilman, H. CRV 1960, 60, 459.
2. (a) Alexander, R.; Attar-Bashi, M. T.; Eaborn, C.; Walton, D. R. M. T 1974, 30, 899. (b) Roberts, R. M. G. JOM 1971, 32, 323.
3. (a) Scott, W. J.; Crisp, G. T.; Stille, J. K. OS 1989, 68, 116. (b) van den Berghe, E. V.; van der Kelen, G. P. JOM 1966, 6, 522.
4. (a) Stille, J. K. AG(E) 1986, 25, 508. (b) Scott, W. J.; McMurry, J. E. ACR 1988, 21, 47.
5. (a) Naumov, S. N.; Manulkin, Z. M. JGU 1935, 5, 281. (b) Lippincott, E. R.; Tobin, M. C. JACS 1953, 75, 4141.
6. (a) Waring, C. E.; Horton, W. S. JACS 1945, 67, 540. (b) Edgell, W. F.; Ward, C. H. JACS 1954, 76, 1169.
7. Milstein, D.; Stille, J. K. JACS 1979, 101, 4992.
8. Farina, V.; Krishnan, B. JACS 1991, 113, 9585.
9. (a) Tamayo, N.; Echavarren, A. M.; Paredes, M. C. JOC 1991, 56, 6488. (b) Somei, M.; Sayaama, S.; Naka, K.; Yamada, F. H 1988, 27, 1585.
10. (a) Labadie, J. W.; Tueting, D.; Stille, J. K. JOC 1983, 48, 4634. (b) Kosugi, M.; Shimizu, Y.; Migita, T. CL 1977, 1423.
11. Kobayashi, T.-a.; Sakakura, T.; Tanaka, M. TL 1985, 26, 3463.
12. Stille, J. K.; Sweet, M. P. TL 1989, 30, 3645.
13. Solberg, J.; Undheim, K. ACS 1987, B41, 712.
14. Herdewijn, P.; Kerremans, L.; Wigerinck, P.; Vandendriessche, F.; Van Aerschot, A. TL 1991, 32, 4397.
15. Scott, W. J.; Stille, J. K. JACS 1986, 108, 3033.
16. Echavarren, A. M.; Stille, J. K. JACS 1987, 109, 5478.
17. Farina, V.; Baker, S. R.; Benigni, D. A.; Hauck, S. I.; Sapino, C., Jr. JOC 1990, 55, 5833.
18. Banwell, M. G.; Cameron, J. M.; Collis, M. P.; Crisp, G. T.; Gable, R. W.; Hamel, E.; Lambert, J. N.; Mackay, M. F.; Reum, M. E.; Scoble, J. A. AJC 1991, 44, 705.
19. Kikukawa, K.; Idemoto, T.; Katayama, A.; Kono, K.; Wada, F.; Matsuda, T. JCS(P1) 1987, 1511.
20. Somei, M.; Yamada, F.; Naka, K. CPB 1987, 35, 1322.
21. Davies, S. G.; Pyatt, D.; Thomson, C. JOM 1990, 387, 381.
22. Echavarren, A. M.; Stille, J. K. JACS 1988, 110, 1557.
23. Crisp, G. T.; Scott, W. J.; Stille, J. K. JACS 1984, 106, 7500.
24. Tanaka, M. S 1981, 47.
25. Papetti, S.; Post, H. W. JOC 1957, 22, 526.
26. Ruf, W.; Renk, T.; Siebert, W. ZN(B) 1976, 31B, 1028.
27. Narula, S. P.; Sharma, R. K.; Lata, S.; Walia, R. IJC(A) 1983, 22A, 246.
28. Wieber, M.; Wirth, D.; Fetzer, I. Z. Anorg. Allg. Chem. 1983, 505, 134.

William J. Scott, J. Howard Jones & Alessandro F. Moretto

Bayer Pharmaceutical Division, West Haven, CT, USA

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