An enantioselective route to the C(1) -C(6) erythronolide unit 10 is described, involving the dioxanone-to-dihydropyran enolate Claisen rearrangement (7 + 8), regio-and stereoselective hydroboration to give 9a, and reductive fragmentation of the heterocyclic template (9c + 10).
The stereocontrolled synthesis of polysubstituted dihydropyrans via a variant of the enolate Claisen rearrangement has recently been described.1 This process of dioxanone-to-dihydropyran conversion is generalized in eq. 1 for one stereochemical series. The all-& orientation of the substituents at the three sps-carbon stereocenters in the product suggested that stereoselective electrophilic addition to the olefin residue could be effected to give a tetrahydropyran with five contiguous asymmetric carbons in the ring.
The realization of this, followed by a cleavage of the heterocyclic template, has provided an efficient route to a synthon for the C( 1) -C(6) portion of the erythronolide B aglycone (1) as described herein.2
The correlation of the macrolide subunit via the seco acid 2 with the appropriate tetrahydropyran system 3 is shown in eq. 2. The heterocycle 3 contains the C(2)-C(5) stereocenters in their correct absolute configurations, a P-halo ether for the reductive fragmentation of the C(l)-0 bond, and an