Titanium Salalen Catalyzed Enantioselective Benzylic Hydroxylation

Abstract

The titanium complex of the cis‐1,2‐diaminocyclohexane (cis‐DACH) derived Berkessel‐salalen ligand is a highly efficient and enantioselective catalyst for the asymmetric epoxidation of terminal olefins with hydrogen peroxide (“Berkessel‐Katsuki catalyst”). We herein report that this epoxidation catalyst also effects the highly enantioselective hydroxylation of benzylic C−H bonds with hydrogen peroxide. Mechanism‐based ligand optimization identified a novel nitro‐salalen Ti‐catalyst of the highest efficiency ever reported for asymmetric catalytic benzylic hydroxylation, with enantioselectivities of up to 98 % ee, while overoxidation to ketone is marginal. The novel nitro‐salalen Ti‐catalyst also shows enhanced epoxidation efficiency, as evidenced by e.g. the conversion of 1‐decene to its epoxide in 90 % yield with 94 % ee, at a catalyst loading of 0.1 mol‐% only.

Visible-Light-Promoted Reduction of Epoxides, Hydroxysulfonates, and Halohydrines with Alkyltitanium Alkoxides

“…Being readily available and nontoxic, titanium reagents and catalysts have been employed in remarkably diverse organic transformations including oxidation, reduction, and C–C bond forming reactions. − Low valent titanium species, especially Ti III compounds, are powerful reducing agents capable of reacting with carbonyl, imine, oxime, epoxide, acylaziridine, halide, hydroxyl, oxazoline, and other functional groups (Scheme A). − These reagents are air-sensitive and typically prepared in situ by the reduction of an available Ti IV compound with a suitable reductant such as K, Zn, Mn, or Mg metals or a Grignard reagent. Recently, Ti III/IV catalysis was successfully merged with photoredox catalysis, where reduction of Ti IV was achieved by the oxidative quenching of a photocatalyst .…”

Visible-Light-Promoted Reduction of Epoxides, Hydroxysulfonates and Halohydrines with Alkyltitanium Alkoxides

“…Ester, amide, alkyne, sulphone, and remote bromide groups were stable under the reaction conditions.Being readily available and non-toxic, titanium reagents and catalysts have been employed in remarkably diverse organic transformations including oxidation, reduction and C-C bond forming reactions. [1][2][3][4] Low valent titanium species, especially Ti III compounds, are powerful reducing agents capable of reacting with carbonyl, imine, oxime, epoxide, acylaziridine, halide, hydroxyl, oxazoline and other functional groups (Scheme 1A). 5-10 These reagents are air-sensitive and typically prepared in situ by the reduction of an available Ti IV compound with a suitable reductant such as K, Zn, Mn, Mg metals or a Grignard reagent.…”