[7440-31-5]  · Sn  · Tin  · (MW 118.71)

(with HCl, reduces a variety of functional groups;2 stereoselective allylation of carbonyl compounds;3 in situ generation of tin enolates for directed aldol reactions4)

Physical Data: mp 232 °C; bp ~2270 °C; d 7.31 g cm-3.

Solubility: insol water, organic solvents; reacts with mineral acids.

Form Supplied in: foil, moss, powder, granules, shot, and wire.

Preparative Methods: activated form is prepared from Tin(II) Chloride in THF by reduction with Lithium Aluminum Hydride5 or Potassium metal;6 tin amalgam is prepared from Mercury(II) Chloride and 30-mesh Sn in water;7 tin-copper couple is prepared from Copper(II) Acetate and 30-mesh tin in acetic acid.8

Handling, Storage, and Precautions: incompatible with strong acids and strong oxidizing agents; powdered form is air and moisture sensitive and should not be inhaled or contacted with the eyes or skin; amalgam is stored under water; tin-copper couple is stored under ether.

Functional Group Reductions.

The use of tin and Hydrochloric Acid is a classical method for the reduction of a variety of functional groups.2 However this procedure has decreased in importance since the development of catalytic hydrogenation and of metal hydride reducing agents, and the harsh reaction conditions (strong acids and high temperatures) are often incompatible with other functional groups. Many reductions effected by tin are more conveniently carried out with Tin(II) Chloride, which is soluble in some organic solvents. Nevertheless, the method is still used, most notably for the reduction of aromatic nitro compounds to amines, for which metal hydrides are less effective (see Lithium Aluminum Hydride). Representative examples of standard procedures which utilize Sn/HCl include the reductions of 2,6-dibromo-4-nitrophenol to the aminophenol,9 2,4,6-trinitrobenzoic acid to the triamine (eq 1),10 and nitrobarbituric acid to the amine (uramil).11 Aromatic nitro group reductions with tin and hydrochloric acid have been employed in the preparation of functionalized paracyclophanes12 and hemispherands.13 8-Nitroquinolines have been reduced to the corresponding amines with a combination of tin and tin(II) chloride.14 In some cases the generated amines undergo further reactions (eq 2).15

Sterically hindered aliphatic vicinal diamines have recently been prepared by Sn/HCl reductions of the corresponding 1,2-dinitro compounds (eq 3).16 Under the same conditions, a geminal dinitro compound is reported to give the corresponding oxime (eq 4).16 N-Nitrosamines are reduced by tin and HCl to the denitrosated amines (eq 5),17 whereas the corresponding Zinc reduction produces the hydrazines.

Examples of reductions of other functional groups by tin and HCl include the reduction of isoquinoline methiodides,18 of tetrahydrocarbazole to hexahydrocarbazole,19 and of 5-(chloromethyl)uracil to thymine (eq 6),20 the selective debromination of 1,6-dibromo-2-naphthol (eq 7),21 and the reduction of anisoin to deoxyanisoin,22 of anthraquinone to anthrone (eq 8),23 and of benzaldehydes to stilbenes.24

Tin amalgam and hydrochloric acid is useful for the selective reduction of the double bond of conjugated enediones in high yield (eq 9)7 and for the controlled reduction of benzils to either benzoins or deoxybenzoins.25 Tin amalgam in Acetic Acid also reduces benzoquinones to hydroquinones.7,26

Tin reductions have also been used for the conversion of arylsulfonyl chlorides to the corresponding thiols27 and for the preparation of Thiophosgene from thiocarbonyl perchloride.28 Metallic tin has recently been used for the in situ generation of low-valent bismuth and titanium species that catalyze cyclizations to 3-hydroxycephems (eq 10).29 A tin-copper couple has been used for the selective debromination of activated dibromides (eq 11),8 in cases where the more commonly employed Zinc/Copper Couple leads to overreduction.

Barbier-Type Allylations and Related Reactions.

The reaction of carbonyl compounds with allylmetal reagents to give homoallylic alcohols is an extremely important reaction in organic synthesis.3,30 Metallic tin can be used for the in situ generation of diallyltin dihalides for subsequent reaction with aldehydes or ketones in good yield (eq 12).31 The procedure is considerably more convenient than that involving isolation of allyltin intermediates and can be carried out in the presence of water.32 Moderate asymmetric induction is observed when the reaction is carried out in the presence of monosodium (+)-diethyl tartrate.33 The yields are improved by sonication34 and this procedure has recently been applied to chain extensions of carbohydrates.35 The reaction can be made catalytic by electrochemical regeneration of the tin reagent.36

A further improvement involves performing the reaction in the presence of Aluminum powder in a THF-water mixture.32 Under these conditions, allyl chloride also reacts37 and yields are improved for reactions of substituted allyl halides. In such cases the diastereoselectivity is dependent on the specific reactants and reaction conditions. For example the Sn/Al reaction of benzaldehyde with crotyl bromide gives the syn diastereoisomer as the major product (eq 13),32 whereas reaction with cinnamyl chloride occurs with exclusive anti selectivity (eq 14).38 Under the same conditions cinnamyl chloride reacts with enals by exclusive 1,2-regioselective addition and complete anti diastereoselectivity and with 2-phenylpropanal with moderate Cram selectivity (eq 15).38 These reactions are compatible with a variety of other functional groups,32,39,40 although in some cases these may induce further reactions (eq 16).40 A mechanistic study of the tin-promoted reactions of allylic iodides with benzaldehydes has recently been reported.41 It has also recently been shown that allylic alcohols undergo similar reactions with metallic tin in the presence of Chlorotrimethylsilane and Sodium Iodide.42 Under these conditions, substituted allylic alcohols undergo carbon-carbon bond formation to the less substituted allylic carbon.42

The Sn/Al procedure has been further extended to the reactions of propargylic halides and such reactions can give both alkynic and allenic products, depending on the reaction conditions (eq 17).43 The direct reaction of metallic tin with simple alkyl halides to give dialkyltin dihalides is an industrially important reaction and is usually restricted to the reactions of alkyl iodides.44 More recently, a phase-transfer catalyzed procedure has been developed that facilitates reactions of alkyl bromides and chlorides.45

Tin Enolates.

Tin enolates are useful intermediates for use in directed aldol reactions.4,46 Tin(II) enolates are usually prepared47 by reaction of enolizable ketones with Tin(II) Trifluoromethanesulfonate, but can also be prepared from reactions of a-bromocarbonyl compounds with activated metallic tin. Such enolates react with aldehydes and ketones under mild conditions to give aldols, generally in high yield (eq 18).48 With a-substituted enolates high syn selectivity is observed (eq 19);48 this is the opposite selectivity to that found with tin(IV) enolates. It has recently been shown that such reactions can be carried out in aqueous media with unactivated tin powder, but that under these conditions the metal enolate is probably not involved; a single-electron-transfer mechanism has been suggested.49 In a related reaction, metallic tin has been used to generate a highly functionalized tin(II) enolate for alkylation of an azetidinone as part of a carbapenam synthesis (eq 20).50

Tin(II) ester enolates can also be prepared by reaction of a-bromo carboxylic acid esters for Reformatsky-type reactions under very mild conditions (eq 21).5 Reaction of an a-diketone or a-keto aldehyde with activated metallic tin produces a tin(II) enediolate that reacts with aldehydes to produce a,b-dihydroxy ketones in high yield (eq 22).51 The diastereoselectivity of this reaction can is controlled by the addition of hexafluorobenzene.

1. (a) Pereyre, M.; Quintard, J.-P.; Rahm, A. Tin in Organic Synthesis; Butterworths: London, 1987. (b) Chemistry of Tin; Harrison, P. G., Ed.; Chapman and Hall: New York, 1989.
2. (a) Hudlicky, M. Reductions in Organic Synthesis; Horwood: Chichester, 1984. (b) COS 1991, 8, Chapters 1.1-4.8.
3. (a) Roush, W. R. COS 1991, 2, 1. (b) Yamamoto, Y.; Asao, N. CRV 1993, 93, 2207.
4. Chan, T.-H. COS 1991, 2, 595.
5. Harada, T.; Mukaiyama, T. CL 1982, 161.
6. Kato, J.; Mukaiyama, T. CL 1983, 1727.
7. Schaefer, J. P. JOC 1960, 25, 2027.
8. Dowd, P.; Marwaha, L. K. JOC 1976, 41, 4035.
9. Hartman, W. W.; Dickey, J. B.; Stampfli, J. G. OSC 1943, 2, 175.
10. Clarke, H. T.; Hartman, W. W. OSC 1932, 1, 444.
11. Hartman, W. W.; Sheppard, O. E. OSC 1943, 2, 617.
12. Sheehan, M.; Cram, D. J. JACS 1969, 91, 3544.
13. Doxsee, K. M.; Feigel, M.; Stewart, K. D.; Canary, J. W.; Knobler, C. B.; Cram, D. J. JACS 1987, 109, 3098.
14. Carroll, F. I.; Berrang, B. D.; Linn, C. P. JMC 1979, 22, 1363.
15. (a) Wear, R. L.; Hamilton, C. S. JACS 1950, 72, 2893. (b) Petrow, V. A.; Stack, M. V.; Wragg, W. R. JCS 1943, 316.
16. Asaro, M. F.; Nakayama, I.; Wilson, R. B., Jr. JOC 1992, 57, 778.
17. Fridman, A. L.; Mukhametshin, F. M.; Novikov, S. S. RCR 1971, 40, 34.
18. Wittig, G.; Streib, H. LA 1953, 584, 1.
19. Gurney, J.; Perkin, W. H., Jr.; Plant, S. G. P. JCS 1927, 130, 2676.
20. Skinner, W. A.; Schelstraete, M. G. M.; Baker, B. R. JOC 1960, 25, 149.
21. Koelsch, C. F. OSC 1955, 3, 132.
22. Carter, P. H.; Craig, J. C.; Lack, R. E.; Moyle, M. OSC 1973, 5, 339.
23. Meyer, K. H. OSC 1932, 1, 60.
24. Stewart, F. H. C. JOC 1961, 26, 3604.
25. Pearl, I. A.; Dehn, W. M. JACS 1938, 60, 57; Pearl, I. A. JOC 1957, 22, 1229.
26. Chang, M.; Netzly, D. H.; Butler, L. G.; Lynn, D. G. JACS 1986, 108, 7858.
27. Hodgson, H. H.; Leigh, E. JCS 1939, 142, 1094.
28. Dyson, G. M. OSC 1932, 1, 506.
29. Tanaka, H.; Taniguchi, M.; Kameyama, Y.; Monnin, M.; Sasaoka, M.; Shiroi, T.; Nagao, S.; Torii, S. CL 1990, 1867.
30. Hoffmann, R. W. AG(E) 1982, 21, 555; Yamamoto, Y. ACR 1987, 20, 243.
31. Mukaiyama, T.; Harada, T. CL 1981, 1527.
32. Nokami, J.; Otera, J.; Sudo, T.; Okawara, R. OM 1983, 2, 191.
33. Boga, C.; Savoia, D.; Tagliavini, E.; Trombini, C.; Umani-Ronchi, A. JOM 1988, 353, 177.
34. Petrier, C.; Einhorn, J.; Luche, J. L. TL 1985, 26, 1449.
35. Schmid, W.; Whitesides, G. M. JACS 1991, 113, 6674.
36. Uneyama, K.; Matsuda, H.; Torii, S. TL 1984, 25, 6017.
37. Uneyama, K.; Kamaki, N.; Moriya, H.; Torii, S. JOC 1985, 50, 5396.
38. (a) Coxon, J. M.; van Eyk, S. J.; Steel, P. J. TL 1985, 26, 6121. (b) Coxon, J. M.; van Eyk, S. J.; Steel, P. J. T 1989, 45, 1029.
39. Mandai, T.; Nokami, J.; Yano, T.; Yoshinaga, Y.; Otera, J. JOC 1984, 49, 172.
40. Nokami, J.; Tamaoka, T.; Ogawa, H.; Wakabayashi, S. CL 1986, 541.
41. Yamataka, H.; Nishikawa, K.; Hanafusa, T. BCJ 1992, 65, 2145.
42. Kanagawa, Y.; Nishiyama, Y.; Ishii, Y. JOC 1992, 57, 6988.
43. Nokami, J.; Tamaoka, T.; Koguchi, T.; Okawara, R. CL 1984, 1939.
44. Oakes, V.; Hutton, R. E. JOM 1965, 3, 472.
45. Ugo, R.; Chiesa, A.; Fusi, A. JOM 1987, 330, 25.
46. Mukaiyama, T. OR 1982, 28, 203.
47. Mekelburger, H. B.; Wilcox, C. S. COS 1991, 2, 99.
48. Harada, T.; Mukaiyama, T. CL 1982, 467.
49. Chan, T. H.; Li, C. J.; Wei, Z. Y. CC 1990, 505.
50. Deziel, R.; Endo, M. TL 1988, 29, 61.
51. Mukaiyama, T.; Kato, J.; Yamaguchi, M. CL 1982, 1291.

Peter J. Steel

University of Canterbury, Christchurch, New Zealand

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