Key factors for high diastereo- And enantioselectivity of umpolung cyclizations of aldehyde-containing allylpalladium intermediates

Two palladium/chiral diphosphine-catalyzed umpolung cyc-lizations of aldehyde-containing allylic acetates and allenes with arylboronic acid are fully investigated to establish key factors in their high stereoselectivities. Both cyclization reactions afford cis-disubstituted pyrrolidine and tetrahydrofuran. These occur in high diastereo- and enantioselectivities through a common cationic (Z)-η¹-allylpalladium, toward which a ring strain generated in the cyclization step leading to trans-isomers biases the equilibrium through η³-η¹-η³-complex in the former cyclization. Varied diastereoselectivities were observed in the formation of five-membered carbocycles and six-membered heterocycles. These reflect release of a ring strain generated in the cyclization step leading to trans-isomers and a different distribution of the (Z)- and the (E)-η¹-allylpalladium intermediates generated by the oxidative addition of allylic acetates to Pd(0) or carbopalladation of allenes, respectively. A steri-cally demanding substituent at the center of the allyl moiety is necessary for high diastereo- and enantioselectivity. The enantioselectivity of the former cyclization was lowered by the presence of organometallic reductants or reagents, possibly causing the formation of neutral η¹-allylpalladium species. We used a chiral allylic acetate containing (E)-deuterium-labeled alkene to demonstrate that the electrophilic attack of the aldehyde to the allyl ligand occurred on the side where the palladium existed, consistent with the Zimmerman-Traxler transition state.