Asymmetric Allylic Alkylation of Cyclic Vinylogous Esters and Thioesters by Pd-Catalyzed Decarboxylation of Enol Carbonate and β-Ketoester Substrates
✍ Scribed by Barry M. Trost; Robert N. Bream; Jiayi Xu
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 159 KB
- Volume
- 45
- Category
- Article
- ISSN
- 0044-8249
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✦ Synopsis
b-Alkoxy a,b-unsaturated ketones are versatile synthons for organic synthesis, as they serve as masked 1,3-dicarbonyl compounds in which the two ketone groups and adjacent carbon atoms may be selectively functionalized. Polysubstituted cyclic vinylogous esters are particularly useful for the synthesis of terpene, alkaloid, and steroidal natural products; [1] a practical method for their synthesis in enantioenriched form is therefore eminently desirable. The catalytic enantiomeric protocol to synthesize enones, such as 3, was reported recently by Fuchs and co-workers, but was limited to monosubstituted enones (R 2 = H), and the relatively harsh conditions may further limit the access to highly functionalized enones. [2] Our strategy aimed to take advantage of an asymmetric allylic alkylation (AAA)/Stork-Danheiser addition sequence to furnish g,g-disubstituted cycloalkenones 3 [Eq. ( 1)]. [3] We initially attempted to access 2 with our previously reported method by alkylating the kinetically generated enolate of 1 with a combination of Pd 0 , methyl allyl carbonate, and a chiral bidentate phosphine ligand. [4] The use of lithium diisopropyl amide (LDA) as the base (Li is essential for regiospecific enolate formation and alkylation) allowed quantitative formation of allylated products. However, we could not improve enantioselectivity beyond 30 %. We there-[
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