title: Catalytic functionalization of unactivated primary C-H bonds directed by an alcohol.
abstract: New synthetic methods for the catalytic functionalization of C-H bonds have the potential to revolutionize the synthesis of complex molecules. However, the realization of this synthetic potential requires the ability to functionalize selectively one C-H bond in a compound containing many such bonds and an array of functional groups. The site-selective functionalization of aliphatic C-H bonds is one of the greatest challenges that must be met for C-H bond functionalization to be used widely in complex-molecule synthesis, and processes catalysed by transition-metals provide the opportunity to control selectivity. Current methods for catalytic, aliphatic C-H bond functionalization typically rely on the presence of one inherently reactive C-H bond, or on installation and subsequent removal of directing groups that are not components of the desired molecule. To overcome these limitations, we sought catalysts and reagents that would facilitate aliphatic C-H bond functionalization at a single site, with chemoselectivity derived from the properties of the catalyst and site-selectivity directed by common functional groups contained in both the reactant and the desired product. Here we show that the combination of an iridium-phenanthroline catalyst and a dihydridosilane reagent leads to the site-selective γ-functionalization of primary C-H bonds controlled by a hydroxyl group, the most common functional group in natural products. The scope of the reaction encompasses alcohols and ketones bearing many substitution patterns and auxiliary functional groups; this broad scope suggests that this methodology will be suitable for the site-selective and diastereoselective functionalization of complex natural products.
authors.affiliation: Department of Chemistry, University of Illinois, Urbana, Illinois 61801, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Simmons
authors.forename: John F
authors.initials: JF
authors.lastname: Hartwig
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D000466:Alkadienes / Q000737:chemistry; D001688:Biological Products / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D002384:Catalysis; D006859:Hydrogen / Q000737:chemistry*; D007202:Indicators and Reagents / Q000737:chemistry; D007495:Iridium / Q000737:chemistry; D007659:Ketones / Q000737:chemistry; D008024:Ligands; D009636:Norbornanes / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D010618:Phenanthrolines / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry
chemical_list: D000438:Alcohols; D000466:Alkadienes; D001688:Biological Products; D007202:Indicators and Reagents; D007659:Ketones; D008024:Ligands; D009636:Norbornanes; D010618:Phenanthrolines; D011725:Pyridines; C439868:1,5-cyclooctadiene; D007495:Iridium; D002244:Carbon; D006859:Hydrogen; C023666:pyridine; D010100:Oxygen