Stereocontrol in Palladium‐Catalyzed Propargylic Substitutions: Kinetic Resolution to give Enantioenriched 1,5‐Enynes and Propargyl Acetates

Abstract

Kinetic resolution during the catalytic allyl-propargyl cross-coupling with chiral starting materials can be accomplished with a chiral Palladium catalyst. These reactions offer ready access to enantiomerically enriched enyne products from simple readily available starting materials.

Congested C–C Bonds by Pd-Catalyzed Enantioselective Allyl–Allyl Cross-Coupling, a Mechanism-Guided Solution

“…Information about the nature of reductive elimination has been previously gained and is represented here for completeness. 6a For this study, substrate ( S ) -Z- 5 was prepared and used in the allyl-allyl cross coupling with allylB(pin) and ( R )- L1 to give ( S ) -E- 6 as the sole coupling product (eq 3). This outcome can be explained as follows: oxidative addition via an anti displacement of the carbonate gives intermediate π-allyl complex N .…”

“…6c This is based on an inner-sphere 3,3'-reductive elimination and uses the crystal structure of ( R )- 4 21 as a template for the ligand conformation. Central to this model is reaction through bis(η 1 -allyl)palladium with the allyl groups directed anti to one another in a chair-like array ( S , Scheme 4).…”

“…Importantly, the barrier to give 16 , a compound inaccessible from the reaction in Scheme 5, is only slightly higher (0.6 kcal/mol) than the barrier to give 15 , a compound previously prepared in 80% yield with high selectivity. 6c …”

“…4,5 Recently, however, our group has developed a number of related palladium-catalyzed allyl-allyl cross-couplings that selectively provide the branched isomer of product in high regio- and enantioselectivity. 6 A critical design feature is the use of a chiral small bite-angle bidentate phosphine ligand, which appears to promote coupling through an inner-sphere 3,3'-reductive elimination pathway shown in structure E (Scheme 1, eq 2). The coupling applies to substrates bearing substitution on both the allylmetal and the allyl electrophile and thereby allows for the synthesis of 1,5-dienes containing tertiary ( F ), quaternary ( G ) and adjacent tertiary ( H ) stereogenic centers.…”

Enantioselective and Enantiospecific Transition-Metal-Catalyzed Cross-Coupling Reactions of Organometallic Reagents To Construct C–C Bonds

“…The authors have also disclosed a related kinetic resolution, in which a chiral ligand enables the selective allylation of one enantiomer of the propargylic substrate, allowing recovery of enantioenriched starting material. 339 More recently, the Morken laboratory reported the Pd-catalyzed stereospecific substitution of allylic acetate 464 with allyl pinacol boronate to deliver enantioenriched 1,5-diene 465 in good yield and with excellent es ( Figure 89 b). 340 This reaction can also be applied to tertiary acetates, which enables the production of 1,5-dienes bearing all-carbon quaternary centers.…”