Hydroformylation of hindered double bonds of natural products with rhodium catalysts: The effect of 3-acetoxy substituent

Andreia F. Peixoto, Mariette M. Pereira, Artur M.S. Silva, Cláudia M. Foca, J. Carles Bayón, Maria José S.M. Moreno, Ana Matos Beja, José A. Paixão, Manuela Ramos Silva

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

Abstract

The hydroformylation of Δ4- and Δ5-steroids, namely cholest-4-ene (1), 3β-acetoxycholest-4-ene (2), 3β-acetoxycholest-5-ene (3), and 3β-acetoxypregn-5-en-20-one (4), was studied using rhodium catalysts modified with P-donor ligands containing electron withdrawing substituents, such as tris(o-tert-butylphenyl)phosphite, tris(o-trifluoromethylphenyl)phosphine and tris(p-trifluoromethylphenyl)phosphine. The effect of temperature, pressure and ligand/Rh molar ratios on the regio- and stereoselectivity of the reaction were studied. Under the reaction conditions assayed, only the Δ4-steroids 1 and 2 are hydroformylated, producing the 4-formyl derivatives with 100 % regioselectivity and 70 and 60 % stereoselectivity for the β isomer, respectively. Δ5-Steroids 3 and 4 either did not react or produced traces of products from the isomerization of the double bond. Among the three catalysts used, only the Rh/tris(o-tert-butylphenyl)phosphite was able to catalyze the hydroformylation of Δ4-steroids. The two new formyl steroids obtained from 1, 4-formyl-5α-H-cholestane (6) and 4-formyl-5β-H-cholestane (7), were isolated as their acetal derivatives and fully characterized by 2D NMR techniques. The structure of the acetal arising from the minor aldehyde product of the reaction was further corroborated by X-ray analysis. The mechanism of the reaction for the conversion of 3β-acetoxycholest-4-ene 2 into 7 was investigated, through the hydroformylation of (1R)-(-)-myrtenyl acetate (5) as a cyclic allylic acetate model. The results show that the reaction does not take place through an allylic intermediate, but that the major aldehyde obtained from 2 undergoes AcOH elimination followed by stereoselective hydrogenation of the α,β-unsaturated aldehyde, leading to 7. © 2007 Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)121-129
JournalJournal of Molecular Catalysis A: Chemical
Volume275
Issue number1-2
DOIs
Publication statusPublished - 17 Sep 2007

Keywords

  • 3β-Acetoxycholest-4-ene
  • 3β-Acetoxycholest-5-ene
  • 3β-Acetoxypregn-5-en-20-one
  • Cholest-4-ene
  • Hydroformylation
  • Myrtenyl acetate
  • Steroids

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