Asymmetric Ketone Diene Coupling via Stereodivergent Copper Catalysis

Area of Science:

• Organic Chemistry
• Asymmetric Synthesis
• Organometallic Chemistry

Background:

• Developing enantioselective methods for carbon-carbon bond formation is crucial in synthetic chemistry.
• Allylcopper intermediates are versatile in mediating nucleophilic additions to carbonyl compounds.
• Controlling stereochemistry in reactions involving dienes remains a significant challenge.

Purpose of the Study:

• To achieve stereodivergent and enantioselective coupling of ketones with dienes.
• To explore the role of different dienyl organometallic reagents in controlling stereochemical outcomes.
• To elucidate the mechanism underlying the observed stereodivergence and enantioselectivity.

Main Methods:

• Stereoselective coupling reactions utilizing ketones and functionalized dienes (1,3-butadienyltriisopropylsilane and 1,3-dienylboronate).
• Employing copper catalysis to generate key allylcopper intermediates.
• Utilizing Density Functional Theory (DFT) calculations to investigate reaction mechanisms and intermediates.

Main Results:

• The reaction of 1,3-butadienyltriisopropylsilane with ketones yielded syn-(E)-adducts with high enantioselectivity.
• The reaction of 1,3-dienylboronate with ketones afforded anti-(Z)-adducts with high enantioselectivity.
• Distinct α-silyl-(Z)-allylcopper and α-boryl-(E)-allylcopper intermediates were identified as key to the stereochemical control.

Conclusions:

• The developed methodology enables stereodivergent synthesis of valuable adducts from ketone-diene coupling.
• The choice of dienyl reagent dictates the nature of the allylcopper intermediate and thus the stereochemical outcome.
• DFT studies support the proposed mechanism involving distinct allylcopper intermediates for stereochemical control.