Efficient synthesis of 1alpha-fluoro A-ring phosphine oxide, a useful building block for vitamin D analogues, from (S)-carvone via a highly selective palladium-catalyzed isomerization of dieneoxide to dieneol.

The 1alpha-fluoro A-ring phosphine oxide 1, a useful building block for fluorinated vitamin D analogues, was synthesized from (S)-carvone in 13 synthetic steps, and only five isolations, in 22% overall yield. In the key synthetic step, a highly selective palladium-catalyzed isomerization of dieneoxide 18 to dieneol 20 was achieved using an appropriately selected fluorinated alcohol as a catalytic proton source.

Catalytic asymmetric synthesis of macrocyclic (E)-allylic alcohols from omega-alkynals via intramolecular 1-alkenylzinc/aldehyde additions.

The omega-alkynals yielded macrocyclic (S)-allylic alcohols in a one-pot reaction sequence involving alkyne monohydroboration, boron to zinc transmetalation, and ((+)-DAIB)-catalyzed enantioselective intramolecular ring closure to the aldehyde function. A general study of this macrocyclization methodology is presented with respect to ligand type, size, and nature of the formed rings.

The practical synthesis of vitamin D analogs: a challenge for process research.

New, highly-potent vitamin D analogs have increasingly come under consideration for the treatment of a variety of diseases as diverse as psoriasis, diabetes, renal osteodystrophy, osteoporosis, leukemia, cancer (breast, colon, prostate), AIDS and multiple sclerosis. This review will present recent efforts for the development of practical syntheses of these valuable compounds using the synthetically convergent Lythgoe approach.