Ultrafast Iron‐Catalyzed Reduction of Functionalized Ketones: Highly Enantioselective Synthesis of Halohydrines, Oxaheterocycles, and Aminoalcohols

Abstract

Am olecularly defined chiral boxmi iron alkyl complex catalyzes the hydroboration of various functionalized ketones and provides the corresponding chiral halohydrines, oxaheterocycles (oxiranes,o xetanes,t etrahydrofurans,a nd dioxanes) and amino alcohols with excellent enantioselectivities (up to > 99 %ee) and conversion efficiencies at low catalyst loadings (as low as 0.5 mol %). Turnover frequencies of greater than 40000 h À1 at À30 8 8Chighlight the activity of this earth-abundant metal catalyst whicht olerates al arge number of functional groups.

First-Row Transition Metal (De)Hydrogenation Catalysis Based On Functional Pincer Ligands

“…The spin density distribution in the four-coordinate, divalent iron complex with a 1,3-bis(2pyridylimino)isoindolines ligand was examined by means of 13 C NMR spectroscopy. 208 Iron, cobalt, and manganese complexes with this family of ligands were utilized in enantioselective ketone reduction, 209 enantioselective ketone hydrosilylation, 210,211 and enantioselective ketone hydroboration. 212,213 2.1.3.…”

Low-Valence Anionic α-Diimine Iron Complexes: Synthesis, Characterization, and Catalytic Hydroboration Studies

“…Catalyst 1 -[K­([18]­c-6)­(thf) 0.5 ] therefore represents one of the most active iron catalysts for the hydroboration of ketones reported to date. For comparison, a turnover frequency of 43 500 h –1 at −30 °C was reported by Gade and co-workers for 4′-fluoroacetophenone hydroboration of HBPin using the current state-of-the-art bis­(oxazolinyl-methylidene)­isoindoline iron catalyst …”

“…As already mentioned in the Introduction, it is a key challenge to develop earth-abundant transition metal catalysts . The catalytic hydroboration of carbonyl compounds using pinacolborane (HBpin) was chosen as a proof of principle, which is an important organic reaction and affords widely used borate esters and the corresponding alcohols by facile hydrolysis. , This catalytic reaction has been intensively studied using precious metal catalysts, but there has also been recent progress in using 3d metal complexes based on Mn, Co, Ni, and Fe. − Although there is a number of reports on iron-catalyzed alkene hydroboration, only a few examples for the hydroboration of carbonyl compounds are described in literature. Findlater and co-workers reported the hydroboration of ketones and aldehydes with HBpin (1.5 equiv.)…”

“…Recently, Gade and co-workers showed that a chiral bis­(oxazolinyl-methylidene)­isoindoline iron alkyl complex is able to catalyze the hydroboration of various functionalized ketones, which led to chiral halohydrines, oxaheterocycles, and amino-alcohols after workup. These reactions were performed at −30 °C and achieved remarkable turnover frequencies of more than 40 000 h –1 …”

Tackling N‐Alkyl Imines with 3d Metal Catalysis: Highly Enantioselective Iron‐Catalyzed Synthesis of α‐Chiral Amines

“…Our previous studies established iron(II) alkyl complexes 1 supported by the bis(oxazolinylmethylidene)isoindoline (“boxmi”) pincer ligand as suitable precatalysts for the enantioselective hydroboration of various functionalized ketones . Their high activity and excellent selectivity after initial conversion of the alkyl to the active hydrido species, combined with the observed tolerance towards ketones bearing amino groups, motivated us to expand this methodology to the reduction of N ‐alkyl imines, and thus a class of compounds which hitherto eluded this type of transformation.…”