Abstract
Axially chiral, enantiopure 1,1'‐binaphthyl‐2‐carboxylic acids (BINA‐Cox) have recently been introduced as chiral ligands for transition metal catalysis. Together with equimolar, co‐catalytic amounts of Ti(OiPr)4 and water they form an in situ catalyst that performs the asymmetric catalytic hydroalkoxylation of 2‐allylphenols to 2‐methylcoumarans at high temperature (240 °C, microwave heating). The synthesis of reference ligand 2'‐MeO‐BINA‐Cox (L1) has been optimized and performed at molar scale. Synthetic routes have been developed to access a variety of substituted BINA‐Cox ligands (>30 examples), which have been tested for ligand effects on the reference asymmetric cyclization of 2‐allylphenol. The substrate range of asymmetric catalytic hydroalkoxylation has been explored through systematic substrate structure variations to define scope and limitations of the titanium‐catalyzed process. The new substrates 2‐(1‐vinylcycloalkyl)phenols (1j, 1k), 2‐(2‐vinylphenyl)propan‐2‐ol (1t), and 2'‐vinyl‐[1,1'‐biphenyl]‐2‐ol (1u) are shown to undergo asymmetric catalytic cyclization to benzodihydrofurans and benzo[c]chromene, respectively.
Highlights
Chiral steering ligands for asymmetric catalysis with transition metal compounds mostly rely on phosphane, phosphite, heterocyclic imine, amine, imine, N-heterocyclic carbene, alkene, alcohol or phenol donors, and combinations thereof.[1]
We have recently described an intramolecular asymmetric catalytic hydroalkoxylation of 2-allylphenols (1) to 2-methylcoumarans (2) that is catalyzed by a peculiar titanium complex generated by mixing Ti(OR)4, the axially chiral carboxylic acid MeO-BINA-Cox (L1) and H2O in a 1:1:1 ratio.[19]
An evaluation of such pathways pointed to Miyano's synthesis of-2′-methoxy-(1,1′-binaphthyl)-2-carboxylic acid (MeOBINA-Cox; L1) as the best option for establishing an economic, scalable and enantioselective route to binaphthyl-2-carboxylic acid derivatives, and that L1 could serve as synthetic platform to access modified ligand structures
Summary
Chiral steering ligands for asymmetric catalysis with transition metal compounds mostly rely on phosphane, phosphite, heterocyclic imine, amine, imine, N-heterocyclic carbene, alkene, alcohol or phenol donors, and combinations thereof.[1]. The precursor 1-bromo-2-methoxynaphthalene required for the key SNAr-reaction (via Grignard reagent 9) has often been prepared by methyl iodide alkylation from commercial 1bromo-2-naphthol.[40] A more economic access at large scale is by bromination of the fragrant compound 2-methoxynaphthalene, which is high-yielding and selective when performed in acetic acid as solvent (see Table S3 for variations).[41]
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