Aldol-type reactions Bismuth

Another important main group metal based Lewis acid catalyst in the aldol reaction is bismuth(III) compounds because of low toxicity, low cost, and good stability. Numerous examples of aldol and aldol-type reactions have been studied using bismuth(III) salts, especially BiCL and Bi(OTf)3, in catalytic amounts (188). 

The first example bismuth-catalyzed aldol reaction was reported by Wada and Akiba and co-workers in 1988, in which 5 mol% of Bids mediated the Mukaiyama aldol reaction efficiently at room temperature (Scheme 48) (189). Subsequently, metallic iodide-activated bismuth(III) chloride, and Bi(OTf)3, were also examined for the Mukaiyama aldol reactions in organic solvents or ionic liquids (190-193). An extension of bismuth triflate catalyzed aldol or aldol-type reaction to the synthesis of substituted 3,4-dihydro-2if-l-benzopyrans has also been reported by Mohan and co-workers (Scheme 49) (194). 

Bismuth tris-trifluoromethanesulfonate has been found to be an efficient catalyst for the Mukaiyama aldol-type reactions (Equation (8.14)). The catalytic activity of this catalyst is higher than the one reported for the rare earth triflates M(OTf)3 (M = Sc, Ln). In its presence the mechanism involves a transmetallation step [33]. The catalyst s water stability allows the recovery and recycling. 

The reaction of an a-halo carbonyl compound with zinc, tin, or indium together with an aldehyde in water gave a direct cross-aldol reaction product (Eq. 8.90).226,227 A direct Reformatsky-type reaction occurred when an aromatic aldehyde reacted with an a-bromo ester in water mediated by zinc in low yields. Recently, it was found that such a reaction mediated by indium was successful and was promoted by son-ication (Eq. 8.91).228 The combination of BiCl3-Al,229 CdCl2-Sm,230 and Zn-Et3B-Eb0231 is also an effective mediator. Bismuth metal, upon activation by zinc fluoride, effected the crossed aldol reaction between a-bromo carbonyl compounds and aldehydes in aqueous media. The reaction was found to be regiospecific and syn-diastereoselective (Eq. 8.92).232... 

Keywords Aza-Sakurai allylationreaction Bismuth triflate C-C bond formation Mannich-type reaction Mukaiyama aldol reaction /V-AI koxycaihony I am ino sulfones Silyl nucleophiles... 

Bismuth chloride (16 mg, 0.05 mmol) and dry dichloromethane (3 ml) were placed in a 50-ml two-necked flask under nitrogen. An aldehyde (1.1 mmol) and a silyl enol ether (1.0 mmol) were added sequentially and the resulting reaction mixture was stirred at room temperature. The reaction was quenched with methanol/1 M HCl (10/1, 0.1 ml), water (10 ml) is added, and the product was extracted with dichloromethane (10 ml) three times. After drying, the solvent was removed in vacuo to leave a crude product, which was purified on thin layer chromatography to afford the corresponding aldol in good yield. A similar procedure was also applicable to the Michael-type reaction [91BCJ990]. 

The use of polymer-supported bismuth catalysts for organic synthesis is highly attractive since this approach combines the advantages of the relative nontoxicity of bismuth salts with their easy separation and recyclability after reaction [131]. For example, microencapsulated Bi(0Tf)3 xH20 in polystyrene has been successfully reported for the methoxymethylation of alcohols, allylation of aldehydes, Michael-type and aldol reactions as well as Baeyer-Villiger oxidations [132]. 

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