In the Sharpless asymmetric epoxidation of chiral secondary allylic alcohols, one substrate enantiomer is predominantly converted to the anti-epoxy alcohol. We herein report the first highly syn-selective epoxidation of terminal allylic alcohols using a titanium salalen complex as catalyst, at room temperature, and aqueous hydrogen peroxide as oxidant. With enantiopure terminal allylic alcohols as substrates, the epoxy alcohols were obtained with up to 98 % yield and up to > 99 : 1 dr (syn). Catalyst loadings as low as 1 mol % can be applied without eroding the syn-diastereoselectivity. Modification of the allylic alcohol to an ether does not affect the diastereoselectivity either [> 99 : 1 dr (syn)]. Inverting the catalyst configuration leads to the antiproduct, albeit at lower dr (ca. 20 : 1). The synthetic potential is demonstrated by a short, gram-scale preparation of a tetrahydrofuran building block with three stereocenters, involving two titanium salalen catalyzed epoxidation steps.

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.

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.

In der asymmetrischen Sharpless-Epoxidierung von chiralen, sekundären Allylalkoholen wird ein Substratenantiomer bevorzugt zum anti-Epoxyalkohol umgesetzt. In dieser Arbeit stellen wir die erste hoch syn-selektive Epoxidierung von terminalen Allylalkoholen vor. Mit einem Titan-Salalen-Katalysator und H 2 O 2 als Oxidationsmittel werden enantiomerenreine, terminale Allylalkohole mit bis zu 98 % Ausbeute und > 99 : 1 dr (syn) zu Epoxyalkoholen umgesetzt. Diese syn-Selektivität bleibt auch bei niedrigeren Katalysatorbeladungen (bis zu 1 mol-%) erhalten. Auch die Modifizierung der Allylalkoholfunktion zu einem Ether beeinflusst die Diastereoselektivität nicht [> 99 : 1 dr (syn)]. Wird die Katalysatorkonfiguration invertiert, so wird bevorzugt das anti-Produkt gebildet, allerdings mit niedrigerem dr (ca. 20 : 1). Das Anwendungspotential wird am Beispiel der Synthese eines THF-Bausteins mit drei Stereozentren im Grammmaßstab demonstriert, in welcher zwei Ti-Salalen-katalysierte Epoxidierungen durchlaufen werden.