Advancements in copper chemistry: New methods for catalytic couplings.

摘要

A three-component, one-pot coupling sequence was developed which involves E-vinyl ligand 1,4-additions to conjugated enones followed by enolate trapping with aldehydes and propargylic triflates. Yields are good to high for this 6 step, single pot reaction involving four different metals. The efficiently transferred vinyl ligands are prepared in situ, via highly regio- and stereoselective hydrozirconations of 1-alkynes using Schwartz' reagent. Use of lithium trimethylzincate as a methyl anion "shuttle" resulted in a reaction that was catalytic in copper and produced a reactive zinc enolate. The zinc enolate is responsible for the reactivity needed to complete the final carbon-carbon bond forming transformation. The major species present under the reaction conditions were examined and identified by low temperature {dollar}sp1{dollar}H NMR spectroscopy.; Additionally, a new procedure was developed for the 1,4-addition of functionalized organozinc reagents that has the advantage of being catalytic in copper. This process takes advantage of the mild conditions used in the formation of organozincs from alkyl iodides and metallic zinc, and hence allows for the delivery of alkyl ligands containing any of the common electrophilic functional groups associated with Knochel zinc methodology. The major species present under the reaction conditions were identified by low temperature 1H NMR spectroscopy.; Lastly, synthetic strategies toward construction of protected korupensamines A and B were explored and developed. MM2 calculations were used to choose a chiral tether, and methods for the attachment of this tether were shown to be effective. Synthesis of an advanced intermediate just prior to the biaryl coupling was achieved. However, under various conditions, oxidative coupling of a diaryl cuprate to the desired korupensamines was not observed. Further molecular modeling revealed that the probable cause for no coupling was the use of too short a tether.