Acetoxyl group directed cyclization promoted by SmI2: directing group determined stereocomplementarity

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Stereoselective Synthesis

Background:

• Ketyl-olefin coupling reactions are valuable for forming carbon-carbon bonds.
• Controlling diastereoselectivity in these reactions is crucial for synthesizing complex molecules.
• Samarium(II) iodide (SmI2) is a versatile reducing agent used in organic synthesis.

Purpose of the Study:

• To investigate the stereochemical outcome of SmI2-promoted ketyl-olefin coupling cyclizations.
• To achieve stereodivergent synthesis of epimeric five-membered-ring alcohols.
• To explore the influence of substrate functionalization (hydroxy ketone vs. acetate) on diastereoselectivity.

Main Methods:

• Utilized samarium(II) iodide (SmI2) as the key reagent for promoting ketyl-olefin coupling cyclizations.
• Employed delta-hydroxy ketone (1) and its corresponding delta-acetoxy ketone (3) as substrates.
• Analyzed the diastereoselectivity of the resulting epimeric five-membered-ring alcohols (e.g., 2 and 4).

Main Results:

• Complete reversal of diastereoselectivity was observed when comparing the cyclization of the hydroxy ketone versus its acetate.
• Stereodivergent synthesis of epimeric five-membered-ring alcohols was successfully achieved.
• The choice of substrate (hydroxy ketone or acetate) dictates the stereochemical outcome of the cyclization.

Conclusions:

• SmI2-promoted ketyl-olefin coupling cyclizations offer a powerful strategy for stereocontrolled synthesis.
• The functional group at the delta-position significantly influences the diastereoselectivity of the reaction.
• This methodology provides access to distinct epimeric alcohol products from a common synthetic pathway.