Ketene acetals reaction with epoxides

In the presence of Lewis acids allyl silanes and stannanes react with epoxides generally at the sterically less demanding carbon atom. Other electron-rich alkenes, such as ketene acetals, can also be used as nucleophiles. The strong Lewis acids required might, however, also lead to rearrangement of the epoxide before addition of the nucleophile can occur (last reaction, Scheme 4.72). 

Trost and Scanlan reported a Pd-catalyzed condensation of a vinyl epoxide 75 and an allyl sulfone 76 in the presence of dppf under neutral conditions [231]. This alkylation allows a room temperature entry to a basic indolizidine ring system as a step towards the synthesis of (+)-aj//o-Pumiliotoxin 339B [232], The modification of allylic alkylations by condensation of a diene 77 with a pronucleophile 78 also leads to C-C bond formation at the allylic position in both 1 1 (79 and 80) and 2 1 (81 and 82) products [233]. Reactions between ketene silyl acetals 83 with allyl... 

A similar transformation can be carried out under milder conditions by taking advantage of silyl ketene acetals, a masked form of the earboxylate dianion. When epichlorohydrin 53 was treated with the ketene acetal 79 in the presence of titanium(IV) chloride, a regioseleetive epoxide ring opening occurs at the less substituted carbon. Treatment of the crude reaction mixture with catalytic p-toluenesulfonic acid promoted a lactonization to the y-butanolide 80 in high overall yield <04T8957>. 

Catalysts formed from Me2Zn and binaphthol 3.7 (R = H) have been used for asymmetric ene-reactions [778]. Enantioselective ring opening of meso-epoxides by n-BuSH is catalyzed by a potassium tartrate/ZnCl2 complex [559, 778, 805]. Mukaiyama and coworkers have shown that reaction of Et2Zn with chiral sulfamides 3.15 (R = PI1CH2, r-Pr) generates Lewis acids [806] that catalyze asymmetric reactions of aldehydes with ketene acetals. 

There have been reports on the synthesis of 2 -deoxynucleosides chain-extended at C-5. The homologue 49 of deoxyadenosine has been prepared from l,2 5,6-di-0-isopropylidene-a-D-allofuranose, with radical deoxygenations at C-2 and C-5, whilst various compounds of type 50 (R=CN, N3, OMe, -CH=CH2, NO2) have been made either by opening of a 5, 6 -epoxide or by addition of nucleophiles to the 5 -aldehyde. ° Other workers have shown that reaction of the same thymidine 5 -aldehyde with the silyl ketene acetal l-r-butoxy-l-(Tbdms)oxyethene gives the product 50 (R=C02Bu ) stereoselectively7 ... 

The reaction of ketene silyl acetals with epoxides would be a potent way for y-lactone synthesis. However, such basic reaction has not been examined for a long time. In 2(X)4, the first example of this type of reaction was reported by Saicic and his group (Scheme 15) [29]. When a stoichiometric amoxmt of TiCl4 was used as a promoter, the reaction of halomethyl epoxide 37 with ketene silyl acetal proceeded to give the desired y-lactone 38. In this case, it was also mentioned that other types of Lewis acids such as BF3-OEt2, ZnCl2, SnCl4, and MesSiOTf are ineffective. 

SCHEME 15 Reaction of epoxides with ketene sllyl acetal. 

V. Maslak, R. Matovic, R.N. Saici6, Reaction of silyl ketene acetals with epoxides a new method for the synthesis of y-butanolides. Tetrahedron 60 (2004) 8957-8966. 

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