4‐Methyltetrahydropyran: a Versatile Alternative Solvent for the Preparation of Chiral BINOL Catalysts and the Asymmetric Alkylation of Aldehydes

We herein report that the highly hydrophobic ether 4-MeTHP constitutes a promising resource for the development of sustainable synthetic methodologies grounded on the use of organometallic reagents. The beneficial effects of 4-MeTHP as reaction media are illustrated in the organolithium-promoted anionic ortho-Fries rearrangement of 1,1’-bi-2-naphthol (BINOL)-based carbamates under bench-type conditions. The use of 4-MeTHP induces a remarkable and unexpected stability of the organolithiums species, enabling the efficient preparation of chiral (bis)carboxamide catalysts. Furthermore, superior performances of 4-MeTHP than other environmentally responsible solvents are observed using the synthesized BINOL catalysts in the asymmetric addition of organozinc reagents to aldehydes. Spectroscopic studies in solution suggest that 4-MeTHP plays a key role in these reactions by inducing the preferential formation of a reactive monomeric dinuclear complex. This methodology allows for the asymmetric assembly of enantioenriched secondary alcohols in good yields and high stereoselectivity, working at 0 °C and under air.