Stannanes toxicity

Legros et al. (2001T2507) carried out the synthesis of acetylquinolines (e.g. 130) via Heck reaction of 3-bromoquinoline (70) and -butyl vinyl ether (Scheme 16) employing either Pd(dba)2 or Pd(OAc)a as the catalyst. In each case it was found that the Heck reaction for this synthesis gave better overall yields than using the Stille reaction (see Section IV.C). Another advantageous point in favor of the Heck is that it avoids the use of toxic stannane. 

Appel MJ, Waalkens-Berendsen DH (2004a) Trichiormethyi-stannane [CAS 993-16-8] Sub-chronic (13 week) orai toxicity study in rats, inciuding a reproduction/deveiopmentai screening study. Zeist, TNO Nutritien and Food Research Institute, July (TNO Repert Ne. V4929). 

To enhance the efficiency of the cyanide addition, these workers subsequently reported a three-component asymmetric synthesis of amino nitriles that avoids the use of the previously mentioned undesirable stannane [74], Thus, as illustrated in Scheme 6.23, treatment of the requisite aniline and aldehyde with HCN (toxic but cheap and suitable for industrial use) at —45°C in the presence of 2.5 mol% 65 leads to the formation of 67 with 86 % ee and in 80 % yield. As was mentioned above in the context of catalytic asymmetric three-component alkylations of imines (see Scheme 6.18), the in situ procedure is particularly useful for the less stable aliphatic substrates (cf. 71—73, Scheme 6.23). The introduction of the o-Me group on the aniline is reported to lead to higher levels of asymmetric induction, perhaps because with the sterically less demanding aliphatic systems, the imine can exist as a mixture of interconverting cis and trans isomers. 

Trialkyltin hydrides are common reagents in organic radical chemistry, but the toxic by-products are extremely difficult to remove from reaction products. To facilitate their removal, a pyrene-functionalized tin hydride has been prepared (entry 20) 25 After standard solution-phase radical reactions with the stannane, filtration through activated carbon traps the tin species to afford pure products. 

The balanced reaction for a synthesis of an intermediate (13.57) for a fluvastatin analogue is shown here. This reaction relies on a vinyl stannane (13.a). Stannanes are toxic and generate large amounts of waste. Calculate the atom economy for this reaction. 

The Stille Coupling is a versatile C-C bond forming reaction between stannanes and halides or pseudohalides, with very few limitations on the R-groups. Well-elaborated methods allow the preparation of differen, products from all of the combinations of halides and stannanes depicted below. The main drawback is the toxicity of the tin compounds used, and their low polarity, which makes them poorly soluble in water. Stannanes are stable, but boronic acids and their derivatives undergo much the same chemistry in what is known as the Suzuki Coupling. Improvements in the Suzuki Coupling may soon lead to the same versatility without the drawbacks of using tin compounds. 

SYN STANNANE, ACETOXYTRICYCLOHEXYL-OSHA PEL TWA 0.1 mg(Sn)/m3 ACGIH TLV TWA 0.1 mg(Sn)/m3 (skin) SAFETY PROFILE Poison by ingestion. When heated to decomposition it emits toxic fumes of Sn. 

Stannanes are toxic and must be handled in an efficient hood at all times. ... 

This reaction generates functionahzed systems by Pd-catalyzed reaction of sp- or j/j-hybridized stannanes with organohalides or triflates [84]. The wider tolerance of functional groups has led to the greater scope of this reaction. Its major drawback is the use of potentially toxic tin reagents. 

Tris(trimethylsilyl)silane 1 can be substituted for toxic stannanes like tributyl-stannane 2 in organic syntheses which involve radicals, because a) sllyl radicals are as efficient as stannyl radicals in the radical-forming step, and b) the Si-H bond strength in tris(trimethylsilyl)silane 1 is only slightly higher than the Sn-H bond strength in tributylstannane 2/ ... 

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