title: Merging allylic C-H bond activation and C-C bond cleavage en route to the formation of a quaternary carbon stereocenter in acyclic systems.
abstract: This protocol describes a diastereoselective approach for the synthesis of complex molecular architectures containing two stereogenic centers in a 1,4 relationship, one of which being an all-carbon quaternary stereogenic center. Such molecules could be intermediates in the synthesis of steroids, for example. Conceived as a single-flask synthetic sequence from ω-ene cyclopropanes, the protocol involves a concerted allylic C-H and C-C bond activation promoted by the Negishi reagent (Cp2Zr(η2-butene)). This zirconium-promenade-based procedure affords bifunctionalized products in high diastereomeric ratios after reaction of ω-ene cyclopropanes with the Negishi complex, followed by a thermal treatment and sequential addition of two different electrophiles. The method proves to be particularly efficient when carbonyl compounds are used as first electrophiles and hydrogen or elemental halides are used as second electrophiles. In addition, it offers the opportunity to create new C-C bonds via remote functionalization of a (sp3)-C-H bond, a result of a copper or copper/palladium transmetalation step that extends the scope of the process to alkyl, acyl and aromatic halide compounds as second electrophiles. The typical described protocol allows the synthesis of the highly diastereo-enriched 2-((1R*,2S*)-2-butyl-2 propylcyclopropyl)ethanol and may provide a new entry to access complex molecular segments of natural products such as steroids or C30 botryococcene. It requires a simple reaction setup and takes ∼18.5 h to run the reaction and 2 h for isolation and purification.
authors.affiliation: The Mallat Family Laboratory of Organic Chemistry, Schulich Faculty of Chemistry and the Lise Meitner-Minerva Center for Computational Quantum Chemistry, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vasseur
authors.affiliation: The Mallat Family Laboratory of Organic Chemistry, Schulich Faculty of Chemistry and the Lise Meitner-Minerva Center for Computational Quantum Chemistry, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Ilan
authors.initials: I
authors.lastname: Marek
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D000431:Ethanol / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; C558934:butylene; D000431:Ethanol; D010165:Palladium; D002244:Carbon; D003300:Copper; D006859:Hydrogen