Enantioselective iodolactonization to prepare ε-lactone rings using hypervalent iodine
Jenna L Payne1, Zihang Deng1, Andrew L Flach1
1Department of Chemistry, Vanderbilt Institute of Chemical Biology, Vanderbilt University Nashville Tennessee 37235-1822 USA jeffrey.n.johnston@vanderbilt.edu.
Chemical Science
|July 8, 2022
Summary
This study introduces a novel method for creating seven-membered rings using enantioselective iodolactonization. The new process achieves high selectivity for larger lactones, overcoming previous limitations in ring-size formation.
Area of Science:
- Organic Chemistry
- Asymmetric Synthesis
Background:
- Enantioselective halolactonization reactions are crucial for synthesizing chiral molecules.
- Existing methods are limited to forming smaller rings (6, 5, and 4-membered) with high selectivity.
- The synthesis of seven-membered ε-lactones with high enantioselectivity remains a significant challenge, especially from conformationally unbiased precursors.
Purpose of the Study:
- To develop the first highly enantioselective method for synthesizing seven-membered ε-lactones.
- To achieve enantioselective 7-exo-trig iodolactonizations of conformationally unbiased ε-unsaturated carboxylic acids.
Main Methods:
- Utilizing a bifunctional BAM catalyst in combination with iodine (I2).
- Employing a hypervalent iodine(III) reagent, phenyliodine(III) diacetate (PIDA).
- Investigating the reaction of conformationally unbiased ε-unsaturated carboxylic acids.
Main Results:
- Achieved the first highly enantioselective 7-exo-trig iodolactonizations of conformationally unbiased ε-unsaturated carboxylic acids.
- Demonstrated the effectiveness of the combined catalytic system (BAM catalyst, I2, PIDA).
- Successfully synthesized seven-membered ε-lactones with high stereocontrol.
Conclusions:
- This work overcomes the limitations of previous halolactonization methods regarding ring size and selectivity.
- The developed methodology provides a powerful new tool for accessing complex chiral seven-membered lactones.
- The findings open new avenues for the synthesis of medicinally relevant compounds containing medium-sized rings.
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