The Mitsunobu reaction is versatile and widely-used in organic synthesis for the protection of and inversion of enantiomerically-pure alcohol substrates.1 However, the reaction rate dramatically decreases with secondary alcohols. It has been previously reported2 that the use of sonication dramatically accelerates the rate of the Mitsunobu reaction of hindered substrates. Our current work explores the reaction pathway to investigate if the rate enhancement is due to an alternate radical mechanism as opposed to the classically accepted ionic mechanism. Mitsunobu reactions of enantiomerically-pure secondary alcohols of (+) and (-) menthol were carried out under sonication conditions in tetrahydrofuran (THF). The product distribution from each reaction was studied with 1H NMR spectroscopic techniques. In a classical Mitsunobu reaction, the enantiomerically-pure alcohol would cleanly invert its stereochemical configuration at the alpha -carbon and lead to one product . However, the NMR analysis showed an unequal mixture of diastereomers, which suggests tandem operation of an alternate or free-radical pathway along with an ionic pathway under sonication conditions. Efforts are underway to compare the product ratio with change in solvent, namely, inhibitor-free THF vs. THF with BHT inhibitor as solvents. &lt;!--[if supportFields]&gt;&lt;spanstyle='mso-element:field-begin;mso-field-lock:yes'&gt;&lt;/span&gt;ADDIN MendeleyBibliography CSL_BIBLIOGRAPHY &lt;span style='mso-element:field-separator'&gt;&lt;/span&gt;&lt;![endif]--&gt; (1) Swamy, K. C. K.; Kumar, N. N. B.; Balaraman, E.; Kumar, K. V. P. P. Chem. Rev. (Washington, DC, United States) 2009, 109, 2551. (2) Lepore, S. D.; He, Y. J. Org. Chem. 2003, 68, 8261. &lt;!--[if supportFields]&gt;&lt;span style='font-size:12.0pt;font-family:"Cambria",serif;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:"MS Mincho";mso-fareast-theme-font:minor-fareast;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:AR-SA'&gt;&lt;spanstyle='mso-element:field-end'&gt;&lt;/span&gt;&lt;/span&gt;&lt;![endif]--&gt;

Expeditious, radical pathway for sonication assisted Mitsunobu reaction of hindered secondary alcohols

249th National Meeting (2015)

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