138924-21-7Relevant articles and documents
New strategies for the synthesis of vitamin D metabolites via Pd-catalyzed reactions
Trost, Barry M.,Dumas, Jacques,Villa, Marco
, p. 9836 - 9845 (2007/10/02)
The invention of new palladium-catalyzed reactions offers new insights into synthetic strategies directed toward the vitamin D system. The palladium-catalyzed cycloisomerization of 1,6- and 1,7-enynes to dialkylidenecycloalkanes permits a lynchpin approach to the A ring of vitamin Ds. Using the thioacetal of formaldehyde, the proper subunits containing the olefin and the acetylene were attached. Pd(2+) effected cycloisomerization to an A ring subunit. A more effective strategy evolved from the evolution of a Pd-catalyzed alkylative cyclization of enynes. Whereas prior work established the feasibility of this process for 1,6-enynes, model studies reported herein demonstrate the feasibility of its extension to 1,7-enynes. This reaction permits the creation of a new concept for vitamin D synthesis wherein A ring formation is concomitant with its attachment to an appropriate CD fragment. An asymmetric synthesis of the requistite 1,7-enyne required six steps. Bromomethylenation of Grundmann's ketone and its side chain hydroxylated derivative proceeded with excellent geometrical selectivity (>30:1) using the Wittig reaction. A Pd catalyst generated from (dba)3Pd2·CHCl3 and triphenylphosphine stitched together these two units in a single step resulting in syntheses of alphacalcidiol and calcitriol.
