Pd-catalyzed carbocyclization-Negishi cross-coupling cascade: a novel approach to 1alpha,25-dihydroxyvitamin D3 and analogues.
[reaction: see text] A mild palladium-catalyzed cascade has been used for the synthesis of the hormone 1alpha,25-dihydroxyvitamin D3 (calcitriol, 1a) and its analogues 1b and 1c. This one-pot process involves two consecutive transformations at room temperature: An initial palladium-catalyzed 6-exo-cyclocarbopalladation of vinyl triflates followed by a Negishi cross-coupling reaction with an alkenyl zinc. This novel strategy opens new possibilities for the preparation of a variety of new vitamin D analogues of therapeutic potential, particularly with modifications at the triene and/or ring-A.
Gómez-Reino
Clara
C
Departamento de Química Orgánica y Unidad Asociada al CSIC, Universidad de Santiago de Compostela, E-15782 Santiago de Compostela, Spain.
Vitale
Cristian
C
Maestro
Miguel
M
Mouriño
Antonio
A
D002384:Catalysis; D003500:Cyclization; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000138:chemical synthesis
C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D010165:Palladium