Enantioselective Heck Arylations of Acyclic Alkenyl Alcohols Using a Redox-Relay Strategy

On the basis of key mechanistic insight recently garnered in the exploration of selective Heck reactions, we report here an enantioselective variant that delivers β-, γ-, or δaryl carbonyl products from acyclic alkenol substrates

Erik W. Werner; Tian-Sheng Mei; Alexander J. Burckle; Matthew S. Sigman


Scholarcy highlights

  • Progress in the development of asymmetric Heck couplings of arenes and acyclic olefins has been limited by a tenuous understanding of the factors that dictate selectivity in migratory insertion and β-hydride elimination
  • Alkenes that engage in migratory insertion typically require an adjacent functional group to polarize the double bond for site-selective addition and enhanced reactivity
  • An electronically biased alkene of this type is necessary for two reasons: First, the charge distribution in A dictates site selectivity of the alkene insertion into the metal–aromatic group bond, and, second, these simple substrates oblige β-hydride elimination from B of a single C–H bond in the formation of C
  • We report a Pd-catalyzed enantioselective redox-relay Heck reaction of acyclic, alkenyl alcohols where the addition of the organometallic to the alkene is coupled with oxidation of the alcohol by migration of the metal through the alkyl chain
  • This strategy would require the discovery of a catalyst sensitive to the subtle electronic differences between the carbons α and β to the alcohol in E and capable of distinguishing between electronically similar C–H bonds on the basis of their relative steric environments
  • This suggested the use of aryldiazonium salts as the arene source. These reagents have not been reported in enantioselective carbon–carbon bondforming reactions of this sort because of their likely incompatibility with common, chiral phosphine-based ligands. Despite this lack of precedent, we investigated the use of chiral pyridine oxazoline ligands, which were hypothesized to be compatible with aryldiazonium salts because of their reduced Lewis basicity relative to phosphine ligands
  • Minor amounts of the β-aryl carbonyl products, a result of insertion at the alternative alkenyl carbon, were isolated by using these substrates

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