**1. Introduction**

The availability of enantiomerically pure or enriched compounds is crucial for several different fields of chemistry including pharmaceutical, biological, agricultural, and materials chemistry [1,2]. The high demand for chiral compounds has inspired extensive research into the development of practical and efficient methods for their preparation. One of the main tools for obtaining enantiomerically pure compounds is asymmetric catalysis. In the field of asymmetric catalysis, enantiomerically pure catalysts are employed to transform prochiral or racemic substrates into valuable enantioenriched compounds.

Chiral metal–salen complexes are privileged catalysts, meaning that they are demonstrating enantioselectivity over a wide range of reactions and substrates [3,4]. Salen ligands have attracted much attention due to the fact of their tunable steric and electronic properties as well as their ability to coordinate a large number of different metal ions and stabilize them in various oxidation states [5,6]. In addition, the commercial availability of starting materials, such as enantiomerically pure vicinal diamines, and well-established synthetic procedures allows for the facile preparation of a wide variety of enantiomerically pure salen ligands and their corresponding metal complexes in high yields (Scheme 1).

$$\begin{array}{ccccccccc} \underset{\begin{subarray}{c}\mathbf{a}\_{1},\ldots,\mathbf{a}\_{k} \\ \mathbf{a}\_{1},\ldots,\mathbf{a}\_{k} \end{subarray}} & \underset{\begin{subarray}{c}\mathbf{a}\_{2},\ldots,\mathbf{a}\_{k} \\ \mathbf{a}\_{2},\ldots,\mathbf{a}\_{k} \end{subarray}} & \underset{\begin{subarray}{c}\mathbf{a}\_{1},\ldots,\mathbf{a}\_{k} \\ \mathbf{a}\_{2},\ldots,\mathbf{a}\_{k} \end{subarray}} & \underset{\begin{subarray}{c}\mathbf{a}\_{1},\ldots,\mathbf{a}\_{k} \\ \mathbf{a}\_{2},\ldots,\mathbf{a}\_{k} \end{subarray}} & \underset{\begin{subarray}{c}\mathbf{a}\_{1},\ldots,\mathbf{a}\_{k} \\ \mathbf{a}\_{2},\ldots,\mathbf{a}\_{k} \end{subarray}} & \underset{\begin{subarray}{c}\mathbf{a}\_{1},\ldots,\mathbf{a}\_{k} \\ \mathbf{a}\_{2},\ldots,\mathbf{a}\_{k} \end{subarray}} & \underset{\begin{subarray}{c}\mathbf{a}\_{1},\ldots,\mathbf{a}\_{k} \\ \mathbf{a}\_{2},\ldots,\mathbf{a}\_{k} \end{subarray}} & \underset{\begin{subarray}{c}\mathbf{a}\_{1},\ldots,\mathbf{a}\_{k} \\ \mathbf{a}\_{2},\ldots,\mathbf{a}\_{k} \end{subarray}} \end{array}$$

**Scheme 1.** The synthesis of enantiomerically pure salen ligands and corresponding metal–salen complexes. The ligand synthesis is a Schiff base reaction. The formation of the metal–salen complex is illustrated as the insertion of the metal in oxidation state +II followed by oxidation in air to oxidation state +III.

Epoxides represent an important class of compounds in organic synthesis due to the fact of their high availability and facile, stereoselective, and often regioselective nucleophilic ring-opening, leading to multifunctional organic compounds in very few steps [7]. Achiral and racemic epoxides can be easily prepared by the oxidation of simple alkene precursors, and much effort has also been focused on the development of enantioselective epoxidations [8].

The asymmetric ring-opening (ARO) of epoxides affords enantiopure vicinal difunctionalized organic compounds with two adjacent stereocenters [9,10]. The relative stereochemistry of two stereocenters in the ring-opened product depends on the configuration of the epoxide (Scheme 2). The use of chiral Lewis acids, such as metal–salen complexes, has been shown to significantly increase the reactivity and enantioselectivity of ARO reactions. An alternative way of obtaining the same product would be to first perform an enantioselective epoxidation, followed by selective ring-opening of the enantiomerically pure epoxide.

**Scheme 2.** The asymmetric ring-opening of epoxides and the resulting relative stereochemistry of the ring-opened products. Ring-opening of (**a**) cyclic *meso*-epoxides to yield a ring-opened product with *trans*-stereochemistry; (**b**) acyclic *meso*-epoxides and *cis*-epoxides to yield ring-opened product with *syn*-stereochemistry; (**c**) *trans*-epoxides to yield ring-opened product with *anti*-stereochemistry; (**d**) terminal epoxides.

There are two main types of epoxides that have been used in ARO reactions: achiral (*meso*) epoxides and racemic epoxides. In the former case, the desymmetrization of *meso*-epoxides with a suitable optically pure catalyst leads to the formation of chiral vicinally substituted alcohols with *trans*- (for cyclic *meso*-epoxides) and *syn* stereochemistry (for acyclic *meso*-epoxides) in up to 100% yield and enantiomeric excess. In the latter case, the catalyst has to be able to differentiate between the two enantiomers and preferentially transform one of them into the ring-opened product with high regioselectivity and enantioselectivity. This process is a kinetic resolution (KR). While the

maximum yield of the ring-opened product is only 50%, this method also allows for the simultaneous enantioenrichment of the unreacted epoxide, enabling, for example, the preparation of optically enriched terminal epoxides.

In this review, we present an overview of the development and application of metal–salen complexes as catalysts for the ARO of epoxides. Previous reviews in this area have either been focused on the ARO of epoxides in general and covered a number of different salen and non-salen catalysts [9,10] or focused on the use of metal–salen complexes as catalysts for several different reactions [4]. There are also a number of reviews focused on multi-metallic salen complexes [11–13] and heterogeneous salen complexes [14,15] but, again, covering several different types of reactions. As several of the mentioned reviews were published 5–15 years ago, we here provide an up-to-date and comprehensive overview of the field, covering the literature until the beginning of 2020.

## **2. Desymmetrization of** *meso***-Epoxides**
