Synthesis of 1α,25-dihydroxyvitamin D3 analogues with α-hydroxyalkyl substituents at C12

Convergent syntheses of three new analogues of 1 alpha,25-dihydroxyvitamin D-3 with alpha-hydroxyalkyl substituents at C12 (4a-c) are described. The A-ring and triene system of each analogue were assembled by a tandem Pd-catalysed intramolecular cyclization and Suzuki-Miyaura coupling process. The stereoselective introduction of substituents at C12 was achieved by Johnson-Claisen rearrangement on allylic alcohol 15 as the key step. This article is part of a Special Issue entitled 'Vitamin D Workshop'. (c) 2012 Elsevier Ltd. All rights reserved.