title: N-Heterocyclic Carbene-Copper-Catalyzed Group-, Site-, and Enantioselective Allylic Substitution with a Readily Accessible Propargyl(pinacolato)boron Reagent: Utility in Stereoselective Synthesis and Mechanistic Attributes.
abstract: The first instances of catalytic allylic substitution reactions involving a propargylic nucleophilic component are presented; reactions are facilitated by 5.0 mol % of a catalyst derived from a chiral N-heterocyclic carbene (NHC) and a copper chloride salt. A silyl-containing propargylic organoboron compound, easily prepared in multigram quantities, serves as the reagent. Aryl- and heteroaryl-substituted disubstituted alkenes within allylic phosphates and those with an alkyl or a silyl group can be used. Functional groups typically sensitive to hard nucleophilic reagents are tolerated, particularly in the additions to disubstituted alkenes. Reactions may be performed on the corresponding trisubstituted alkenes, affording quaternary carbon stereogenic centers. Incorporation of the propargylic group is generally favored (vs allenyl addition; 89:11 to >98:2 selectivity); 1,5-enynes can be isolated in 75-90% yield, 87:13 to >98:2 SN2'/SN2 (branched/linear) selectivity and 83:17-99:1 enantiomeric ratio. Utility is showcased by conversion of the alkynyl group to other useful functional units (e.g., homoallenyl and Z-homoalkenyl iodide), direct access to which by other enantioselective protocols would otherwise entail longer routes. Application to stereoselective synthesis of the acyclic portion of antifungal agent plakinic acid A, containing two remotely positioned stereogenic centers, by sequential use of two different NHC-Cu-catalyzed enantioselective allylic substitution (EAS) reactions further highlights utility. Mechanistic investigations (density functional theory calculations and deuterium labeling) point to a bridging function for an alkali metal cation connecting the sulfonate anion and a substrate's phosphate group to form the branched propargyl addition products as the dominant isomers via Cu(III) π-allyl intermediate complexes.
authors.affiliation: Merkert Chemistry Center, Department of Chemistry, Boston College, Chestnut Hill, Massachusetts 02467, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Merkert Chemistry Center, Department of Chemistry, Boston College, Chestnut Hill, Massachusetts 02467, United States.
authors.forename: Byunghyuck
authors.initials: B
authors.lastname: Jung
authors.affiliation: Merkert Chemistry Center, Department of Chemistry, Boston College, Chestnut Hill, Massachusetts 02467, United States.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Torker
authors.affiliation: Merkert Chemistry Center, Department of Chemistry, Boston College, Chestnut Hill, Massachusetts 02467, United States.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Hoveyda
mesh_terms: D000475:Alkenes / Q000737:chemistry; D000480:Alkynes / Q000737:chemistry*; D000498:Allyl Compounds / Q000737:chemistry*; D001895:Boron / Q000737:chemistry*; D001896:Boron Compounds / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D007202:Indicators and Reagents; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D008970:Molecular Weight; D010755:Organophosphates / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D000480:Alkynes; D000498:Allyl Compounds; D001896:Boron Compounds; D007202:Indicators and Reagents; D010755:Organophosphates; C030011:carbene; D003300:Copper; D001895:Boron; D008697:Methane