1,n-Glycols as Dialdehyde Equivalents in Iridium-Catalyzed Enantioselective Carbonyl Allylation and Iterative Two-Directional Assembly of 1,3-Polyols

摘要

Nature's vast collection of polyketide natural products comprises thousands of compounds incorporating polyace-tate-derived 1,3-diol or higher 1,3-polyol substructures. Although numerous procedures for the synthesis of these ubiquitous structural motifs have been advanced,'1' the iterative allylmetallation of aldehydes has found exceptionally broad use. For example, asymmetric iterative allyl-chromation (Nozaki-Hiyama coupling), allyltitanation, allylstannation, allylsilation, and allylboration have been employed in synthetic approaches to 1,3-diols and higher homologues. Brown's allylborane (n-C3H5)lpc2B (Ipc = isopinocampheyl) has found the most extensive use in iterative asymmetric carbonyl allylation. Although super-stoichiometric generation of isopinocampheol poses a barrier to large-volume applications, both enantiomers of a-pinene are available at low cost and excellent levels of stereocontrol are observed, making the Brown method attractive for use in academic laboratories. However, use of traditional allylmetallation procedures in iterative two-directional syntheses of 1,3-polyol substructures is prohibited by the instability of malondialdehyde.