The condensation of alpha,beta-unsaturated orthoesters and activated ketones: A stereoselective crotonate Michael equivalent

The acid-catalyzed condensation of $(E)$-triethyl orthocrotonate, (Z)-triethyl orthocrotonate, and triethyl orthoacrylate with activated ketones at 25-100$\sp\circ$C followed by hydrolysis gave a series of $\delta$-keto ester adducts. The process is acid-catalyzed and occurs readily with cyclic and acyclic ketones containing an electron-withdrawing group $\alpha$ to the ketone carbonyl. The general trend in reactivity with respect to the substituents is: RCHO $>$ RCN $>$ RNO$\sb2$ $\gg$ RCOMe $>$ RCO$\sb2$R with cyclopentanones reacting faster than the corresponding cyclohexanones.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)The syn stereochemistry of three condensation products has been proven by independent synthesis, X-ray crystallographic analysis, and NMR analysis of trans-fused lactones obtained by sodium borohydride reduction. The net reaction of the rearrangement-hydrolysis is the diastereoselective (typically $>$80:20) synthesis of a 1,5-dicarbonyl compound from a ketone (donor) and an unsaturated orthoester (acceptor) equivalent to a Michael addition via a Claisen rearrangement.The mechanism for the orthoester condensation most likely consists of a series of equilibria involving the reversible, acid-catalyzed formation of an oxonium ion from the $\alpha$,$\beta$-unsaturated orthoester, reversible complexation of the oxonium ion with ketone, proton loss, (3,3) sigmatropic rearrangement, and reversible acid-catalyzed orthoester formation. The reaction is not a standard catalytic Michael addition since no reaction was observed under orthoester condensation conditions when ethyl crotonate was substituted for the orthoester.The stereochemistry of the condensation is proposed to arise from a rapid, diastereoselective Claisen rearrangement of an allyl vinyl orthoester intermediate. The proven stereochemistry of three orthoester condensation products is consistent with a chair transition state.U of I OnlyETDs are only available to UIUC Users without author permissio