Copper‐Catalysed, Enantioselective Desymmetrisation of meso Cyclic Allylic Bis(diethyl phosphates) with Organozinc Reagents

A highly regio‐, diastereo‐ and enantioselective desymmetrization of five‐, six‐, and seven‐membered meso , cyclic allylic bis(diethyl phosphates) ( 3 – 5 ) with organozinc reagents was developed, using catalytic amounts (10 mol%) of [Cu(OTf)] 2 · C 6 H 6 and two different classes of chiral ligands: Schiff bases 1 and phosphoramidites 2 . Good to excellent enantioselectivities were obtained for every substrate by a subtle balance of ligand structure and experimental conditions. In particular, ee ’s of up to 88 % were obtained for the five‐membered ring substrate 3 with ligands 1cjo and 1cjm using Et 2 Zn (94 % ee with Me 2 Zn, 88 % ee with n Bu 2 Zn). Schiff‐base ligands 1 were not effective with the six‐ and seven‐membered substrates 4 and 5 . The use of phosphoramidite ligands 2 afforded ee ’s of up to 94 % (Et 2 Zn) for the six‐membered ring product 7 , and virtually only one enantiomer ( ee ≥ 98 %, with Et 2 Zn) for the seven‐membered ring product 8 . In addition, the desymmetrisation of the conduritol derivative 10 was obtained, with ee ’s of up to 86 %. In this case, a fully functionalised cyclohexane derivative, containing four contiguous stereocentres and a double bond, was obtained as a single diastereomer and in high enantiomeric excess from an achiral starting material. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)