Allylic Alcohols via Catalytic Asymmetric Epoxide Rearrangement

Abstract

Optically active allylic alcohols can be prepared via rearrangement of epoxides using chiral lithium amides, but other than for a small subset of meso-epoxides, insufficient reactivity and enantioselectivity hamper the existing methods. Furthermore, the chiral reagents are often required in large excess. This study presents a general and highly enantioselective process that, in addition, is based on catalytic amounts (5 mol %) of enantiopure (1S,3R,4R)-3-(1-pyrrolidinyl)methyl-2-azabicyclo[2.2.1]heptane and lithium diisopropylamide as the stoichiometric base. The influence of structural modification of the catalyst is studied in terms of activity, enantioselectivity, and aggregation behavior. The utility of the process is demonstrated by its application to a variety of epoxide derivatives (g94% ee for 11 out of 14 examples), including the formal syntheses of, e.g., a prostaglandin core unit, epibatidine, carbovir, faranal, and lasiol. The system is readily extended to the resolution of racemic epoxides, which allows access to highly enantioenriched epoxides or allylic alcohols, even at conversions near 50%.

The Short-Chain Alcohol Dehydrogenase ABA2 Catalyzes the Conversion of Xanthoxin to Abscisic Aldehyde[W]

“…Alternatively, a second ABA2-catalyzed enzymatic step might be required to transform the 1Ј,2Ј-epoxy group into an allylic alcohol (1Ј-hydroxy-2Ј-ene) (Figure 7). Allylic alcohols can be generated from epoxide rearrangement through basic catalysis (Södergren et al, 2000). Several examples of this reaction are known in organic chemistry, but in all cases a chemical catalyst is required (Kee et al, 2000;Södergren et al, 2000, and references therein).…”

Reactivity of Oxiranes with Organolithium Reagents

“…As for enantioselective deprotonation, the best results are obtained with HCLA bases of type 56 which can be employed as catalyst (10 mol%) in the presence of excess amounts of LDA (2 equivalents) 49,99 . In such conditions, high levels of selectivity are reached with linear and cyclic oxiranes.…”

Expedient Synthesis of Mequitazine an Antihistaminic Drug by Palladium Catalyzed Allylic Alkylation of Sodium Phenothiazinate

“…[21][22][23] To the best of our knowledge, this selective epoxide rearrangement has never been reported earlier for bicyclo[2,2,2]heterocycles containing epoxides. [24][25][26][27][28][29] While three type of products could be obtained, allyl alcohols, aldehyde and saturated alcohols, arising most likely by carbenoid insertion processes, 24-26) the transformation was highly selective and afforded the desired crucial allyl alcohol 6 exclusively, in 96% of isolated yield (see Experimental).…”

“…[21][22][23] To the best of our knowledge, this selective epoxide rearrangement has never been reported earlier for bicyclo[2,2,2]heterocycles containing epoxides. [24][25][26][27][28][29] While three type of products could be obtained, allyl alcohols, aldehyde and saturated alcohols, arising most likely by carbenoid insertion processes, 24-26) the transformation was highly selective and afforded the desired crucial allyl alcohol 6 exclusively, in 96% of isolated yield (see Experimental).Alternatively, we have also discovered that 6 could be efficiently generated via the Shapiro reaction, [30][31][32] by the known trisylhydrazone 7 with excess n-BuLi followed by quenching the nucleophilic vinyllithium reagent with paraformaldehyde.33) After acetylation of the alcohol 6 under standard conditions affording the allylic acetate 8, 34) the critical allylic alkylation step was studied and optimized. Palladium-catalyzed allylic amination is a well-established method for the synthesis of allyl amines.…”