Catalytic Asymmetric Synthesis of Chiral Cyclic Ethers

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Chiral cyclic ethers constitute one of the most important structural units in biologically active compounds. Among many key building blocks reported so far, a-alkenyl-substituted cyclic ethers are widely recognized as the most useful because the alkenyl moiety can be transformed to a wide range of functionalities. In particular, the focal point is the creation of catalytic enantioselective protocols. Here, we focused on a new type of protocol, in which non-activated or non-protected ow-hydroxy allyl alcohols dehydratively cyclize to the corresponding cyclic ethers.Based on the information that a catalytic system combined[CpRu(CHsCN) 3] PF6 with a pyridine-2-carboxylic acid derivative or the corresponding cationic CpRu(IV)-st-allyl carboxylato complex which can convert a 1 : 1 mixture of alcohols and allyl alcohols to allyl ethers with the liberation of water, we developed a new chiral ligand, s-methyl-6-(2-R-naphthalen-l-yl)-pyridine-2-carboxylic acid(R-Naph-PyCOOH). The ligand is characterized by the sterically flexible axial chirality through C(6)-C(1') bond and the adjustability of electronic and steric properties of the naphthalene ring by the R substituent at C(2'). As the result of an investigation of ligand structure-reactivity and selectivity relationships, the combination of Cl-Naph-PyCOOH or its allyl ester with a CpRu complex achieves the cyclization with excellent reactivity and selectivity, giving various a-alkenyl-substituted cyclic ethers, such as tetrahydrofuran, tetrahydro-2H-pyran, coumaran, and chromane, with up to> 99 : 1 enantiomer ratio.