Abstract
Synthesis of 20‐Carbaldehydes and 20‐Carbonitriles of the Pregnane Series Starting with (20S)‐20‐Hydroxymethylpregna‐1,4‐dien‐3‐oneAn efficient six‐step approach to 3‐protected (20S)‐3β‐hydroxypregna‐1,5‐diene‐20‐carbaldehydes 8 with potential importance in the synthesis of vitamin D analogues was developed starting with (20S)‐20‐hydroxymethylpregna‐1,4‐dien‐3‐one (1). Oxidation of the 22‐hydroxy group of 1 by means of periodinane 2 (Dess‐Martin reagent) furnished the aldehyde 3 without epimerization. 3 was protected selectively at C‐22 as dimethyl acetal 5. Isomerization to 6 and subsequent reduction of the 3‐carbonyl group with calcium borohydride furnished the 3β‐alcohol 7a with high stereoselectivity. Cleavage of the acetal to 8a occurred in a homogeneous solution of acetic acid in the presence of small amounts of water and trifluoroacetic acid. After protection of the 3‐OH group 8b–d were obtained in 54% overall yield. The in situ generated aldehyde N,N‐dimethylhydrazones of 3, 8a, and 8b were converted in high yields with excellent chemoselectivity into the nitriles 12, 15a, and 15b with magnesium monoperoxyphthalate hexahydrate. The uniform (20S) stereochemistry of 3 and 8a–d was elucidated by 1H‐NMR investigations.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.