Synthesis of E-α,β-Unsaturated Ketones with Complete Stereoselectivity via Sequential Aldol-Type/Elimination Reactions Promoted by Samarium ­Diiodide or Chromium Dichloride

Abstract

E-α,β-Unsaturated ketones can be obtained with complete E-selectivity by a sequential reaction of dichloroketones with a variety of aldehydes. This transformation was promoted by SmI₂, SmI₂ in the presence of FeCl₃ or CrCl₂. The best results were obtained when CrCl₂ was used as the metallating agent. A mechanism based on a successive aldol-type reaction and a β-elimination is ­proposed to explain these results.

Key words

alkenes - chromium - diastereoselectivity - samarium - ketones - sequential reactions

References and Notes

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• 22e

  To see similar chair transition states in the reaction with CrCl₂, see ref. 11 and 12.

14

General Procedure for the Synthesis of Compounds 3
SmI₂ (3 mmol, 6 equiv) in THF (30 mL), or CrCl₂ (3 mmol, 6 equiv) in THF (13 mL), was added to a stirred solution of 1,1-dichloroketone (0.5 mmol, 1 equiv) and the correspond-ing aldehyde (0.5 mmol, 1 equiv) in THF (2 mL) under nitrogen atmosphere. The reaction was refluxed for 2 h, and then the reaction was quenched by the addition of 1.0 M aq HCl. Standard workup afforded the crude α,β-enones 3 which were purified by flash column chromatography on silica gel (hexane-EtOAc, 10:1), or alternatively filtered through a pad of Celite^®. When FeCl₃·6H₂O (0.06 equiv) was required, this salt was added to the 1,1-dichloroketone (1 equiv) and the corresponding aldehyde (1 equiv) in THF prior to SmI₂ (6 equiv) addition.

15

When the minor diastereomer was not detected E/Z ratio was assigned >98:2.