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.
Kabat
M M
MM
Chemical Synthesis-Process Research, Non-Clinical Development, Pre-Clinical Research and Development, Hoffmann-La Roche Inc., Nutley, New Jersey 07110, USA.
Garofalo
L M
LM
Daniewski
A R
AR
Hutchings
S D
SD
Liu
W
W
Okabe
M
M
Radinov
R
R
Zhou
Y
Y
D000438:Alcohols / Q000737:chemistry; D000081005:Cyclohexane Monoterpenes; D039821:Monoterpenes; D010087:Oxides / Q000138:chemical synthesis* / Q000737:chemistry; D010165:Palladium / Q000737:chemistry; D010720:Phosphines / Q000138:chemical synthesis* / Q000737:chemistry; D013729:Terpenes / Q000737:chemistry*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D000438:Alcohols; D000081005:Cyclohexane Monoterpenes; D039821:Monoterpenes; D010087:Oxides; D010720:Phosphines; D013729:Terpenes; D014807:Vitamin D; D010165:Palladium; C006923:carvone