Epoxide reactions, rearrangement protocols

Certain Lewis acids are known to induce an epoxide-aldehyde rearrangement <01TL8129>, and this chemistry has recently been combined in tandem with metal-mediated allylations. For example, epoxides react with tetraallyltin in the presence of bismuth(III) triflate to give homoallylic alcohols 116. The reaction involves an initial 1,2-shift to form an aldehyde 115, which is then attacked by the allyl tin species <03TL6501>. A similar but operationally more straightforward protocol is available by combining allyl bromide with indium metal, followed by the addition of epoxide <03TL2911>. 

Treatment of 2,3 Cpoxy-l-amines with Lewis acid induces a rearrangement to aziridinium ions that react efficiently with a nucleophiles to give functionalized hydroxy sulfides or hydroxy amines (Equation 23) <1997SL11>. Under the influence of ethylaluminium chloride, an epoxide tethered to an azide undergoes Lewis acid-assisted cyclization followed by an intramolecular Schmidt reaction and subsequent in situ reduction of the intermediate iminium species upon addition of sodium borohydride (Scheme 8). This protocol was used as a key step in a novel synthesis of indolizidine alkaloids of pharmaceutical interest <20030L583, 2004JOC3093>. 

The well-known base-mediated rearrangement of epoxides into allylic alcohols was first reported as an enantioselective process using a chiral base in 1980. Since then, the reaction has received much attention, mostly due to the significance of chiral allylic alcohols in organic synthesis. Major breakthroughs in the area include the use of a substoichiometric amount of chiral base and the development of chiral bases for a true catalytic reaction protocol. Andersson and co-workers have reviewed this area from 1980 to 2001, with emphasis on the period 1997-2001 <2002CSR223>. 

Nafion resins have been used not only for the opening of epoxides but also for their isomerization to aldehydes or ketones [137]. Various other rearrangements and isomerizations are catalyzed by this solid acid, in some cases with selectivities higher than those obtained with other solid catalysts [138-140]. Other reactions that have been studied include the Peterson methylenation of carbonyl compounds [141], hetero-Michael additions to unsaturated ketones [142], the Koch-type carbon-ylation of alcohols to form carboxylic acids [143], dimerization of a-methylstyrene [144], addition of carboxylic acids to olefins [145] and Diels-Alder reactions [146]. Notably, in most cases, reutilization of the catalyst is considered but only after an appropriate washing protocol to regenerate its acidity/activity. 

One of the most used sequential component reactions in the asymmetric construction of chiral compounds is the so-called anion relay chemistry (ARC) [2], This linchpin coupling protocol consists in the alkylation of an anion, generally a silyl lithium dithiane derivative, by an epoxide or an aziridine, resulting in an oxy- or aza-anion, which in the presence of hexamethylphosphoramide (HMPA) or other polar solvent gives a 1,4-Brook rearrangement, thereby leading to a new reactive dithiane anion that is capable of reacting with a second electrophile E+ (Scheme 11.1). 

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