Michael Additions of Highly Basic Enolates to ortho-Quinone Methides

Area of Science:

• Organic Chemistry
• Synthetic Methodology
• Reaction Mechanisms

Background:

• Ortho-quinone methides (o-QMs) are reactive intermediates.
• Efficient synthesis of β-(2-hydroxyphenyl)-carbonyl compounds is valuable.
• In situ generation of reactive species can streamline synthetic routes.

Purpose of the Study:

• To develop a novel, single-flask protocol for generating enolates and o-QMs.
• To synthesize a variety of β-(2-hydroxyphenyl)-carbonyl compounds.
• To investigate the reaction mechanism, including the intermediacy of o-QMs.

Main Methods:

• In situ generation of ketone/ester enolates and o-QMs from silylated precursors.
• Utilizing anhydrous fluoride as the activating agent.
• Reaction of generated intermediates with suitable partners to form products.

Main Results:

• Successful synthesis of diverse β-(2-hydroxyphenyl)-carbonyl compounds.
• Yields ranging from 32-94% achieved in a single laboratory operation.
• Control experiments supported the intermediacy of o-QMs, with isolation of 1,5-dicarbonyl products.

Conclusions:

• A versatile and efficient single-step protocol for synthesizing β-(2-hydroxyphenyl)-carbonyl compounds has been established.
• The method relies on the in situ generation of reactive enolates and o-QMs.
• The findings provide mechanistic insights into the reaction pathway.