On the lipase-catalyzed resolution of functionalized biaryls

Modular Synthesis of Optically Active Tröger’s Base Analogues

“…The functionalization of the tetracyclic Tröger’s base scaffold through hydroxymethyl substituents in positions ortho to the stereogenic nitrogen atoms allows for fundamentally different approaches to the biocatalytic kinetic resolution such as the use of oxidoreductases11 or hydrolases 12. Furthermore, considering our current success in the application of lipases as enantioselective catalysts for the preparation of unnatural axially chiral building blocks such as allenes13 and non‐ C 2 ‐symmetric biaryls14 with primary hydroxyl groups as enzyme‐binding sites, this concept appeared to be most promising. Last but not least, high tolerance towards organic reaction media, independence from sensitive cofactors, and broad commercial availability at low cost have to be considered undoubtedly major advantages of this class of enzymes.…”

Biocatalytic Enantioselective Synthesis of Atropisomers

“…The fast interconversion of the enantiomeric lactone conformers allows for the atroposelective cleavage of the lactone bridge by the addition of nucleophiles under dynamic kinetic resolution. Building on the extensive research dedicated to lipase-mediated atroposelective transformation, Deska and co-workers attempted the DKR of lactone 59 by ring opening using various lipases . This transformation proved sluggish, and only up to 11% conversion to open ester 60 was observed in 0% ee in the presence of Candida antarctica type B lipase after 7 days at 40 °C, while a pig liver esterase (PLE) delivered the product with 13% ee and only 6% conversion under the same conditions (Scheme ).…”

Enzymatic approaches for the preparation of optically active non-centrochiral compounds

“…Thus, attempts to conduct Bringmann's lactone concept on the basis of a hydrolase-catalyzed alcoholytic or hydrolytic opening suffered from very low reactivity and only traces of the desired products (63) were obtained (Scheme 27). 65 In contrast, reduction of the biaryl lactone to the corresponding primary alcohol 64 provided a suitable substrate for a (nondynamic) kinetic resolution by Mucor miehei lipase with moderate enantioselectivity (k rel = 7.8). In 2002, Matsumoto and coworkers presented a successful desymmetrization protocol based on the enantioselective deacetylation of symmetrical 2,6-diacetoxybiaryls (65).…”