Iridium-catalysed highly selective reduction-elimination of steroidal 4-en-3-ones to 3,5-dienes in water

Steroidal 3,5-diene is an important structural motif in steroid drugs. In this report, an iridium-catalyzed reduction-elimination of readily available steroidal 4-en-3-ones is realized to prepare steroidal 3,5-dienes. At a low catalyst loading (S/C = 200), heating 4-en-3-ones in a water-mixed organi...

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Published inGreen chemistry : an international journal and green chemistry resource : GC Vol. 21; no. 8; pp. 2088 - 2094
Main Authors Li, Jide, Tang, Weiping, Ren, Demin, Xu, Jiaxi, Yang, Zhanhui
Format Journal Article
LanguageEnglish
Published CAMBRIDGE Royal Soc Chemistry 2019
Royal Society of Chemistry
Subjects
Chemistry
Chemistry, Multidisciplinary
Column chromatography
Data processing
Dienes
Esters
Formic acid
Green & Sustainable Science & Technology
Green chemistry
Inert atmospheres
Iridium
Ketones
NMR
Nuclear magnetic resonance
Physical Sciences
Recrystallization
Reduction
Regioselectivity
Science & Technology
Science & Technology - Other Topics
Steroids
Substrates
ALCOHOLS
ALKENES
ASYMMETRIC TRANSFER HYDROGENATION
DEHYDROGENATION
FORMIC-ACID DECOMPOSITION
GREEN CHEMISTRY
CONJUGATED DIENES
AEROBIC OXIDATION
ALKYNYLCARBONYL COMPOUNDS
EFFICIENT
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Summary:Steroidal 3,5-diene is an important structural motif in steroid drugs. In this report, an iridium-catalyzed reduction-elimination of readily available steroidal 4-en-3-ones is realized to prepare steroidal 3,5-dienes. At a low catalyst loading (S/C = 200), heating 4-en-3-ones in a water-mixed organic solvent with formic acid without inert atmosphere protection afforded the desired 3,5-dienes in moderate to excellent yields. In a gram-scale preparation, recrystallization is used instead of column chromatography to purify products. Excellent functionality tolerance and regioselectivity are featured. Structural moieties such as alkanols (primary, secondary and tertiary), esters (except for formate), tolylates, and ketones (endocyclic or exocyclic) are not affected. Surprisingly, the reduction-elimination only takes place at A-ring 4-en-3-ones. In addition, bicyclic 4-en-3-ones are also viable substrates. Synthetic applications of steroidal 3,5-dienes are demonstrated. Our method can also lead to steroidal 3,5-dienes-3-d (>99% d-incorporation) when DCO2D and D2O are used together.
ISSN:1463-9262
1463-9270
DOI:10.1039/c9gc00654k