Organic Chemistry Portal
Organic Chemistry Highlights

Monday, February 13, 2006
Douglass Taber
University of Delaware

Best Synthetic Methods: Oxidation

Classsically, stoichiometric oxidants have been used to convert alcohols into aldehydes and ketones. A practical alternative is to use air oxidation, with a transition metal catalyst. Usually, a secondary alcohol such as 1 is oxidized much more readily than is a primary alcohol such as 3, as illustrated by the work (Org. Lett. 2005, 7, 1077. DOI: 10.1021/ol047381w) of Jaiwook Park of Pohang University of Science and Technology in Korea. Tsutomu Katsuki of Kyushu University has developed (Tetrahedron Lett. 2005, 46, 783. DOI: 10.1016/j.tetlet.2004.12.010) a complementary approach, based on UV activation of a Ru complex, that directs the oxidation specifically to primary alcohols such as 4.

Despite the difficulties associated with the disposal of chromium waste, stoichiometric chromium oxidants are still commonly used in organic synthesis. One of the more popular is pyridinium chlorochromate (PCC). Mo Hunsen of Kenyon College in Ohio has developed a way around this difficulty (Tetrahedron Lett. 2005, 46, 1651. DOI: 10.1016/j.tetlet.2005.01.076), using the PCC catalytically, with stoichiometric periodic acid. The alcohol 7, sometimes troublesome to oxidize, responded smoothly.

The carboxylic acid oxidation state can take many forms. The transformation of aldehydes such as 9 to the 2-dihydroimidazole 10, reported (Tetrahedron Lett. 2005, 46, 2197. DOI: 10.1016/j.tetlet.2005.02.025) by Yasuyuki Kita of Osaka University is formally the conversion of the aldehyde to the acid oxidation state. The procedure works well for both aliphatic and aromatic aldehydes. Remarkably, Shlomo Rozen of Tel Aviv University has shown (Org. Lett. 2005, 7, 2177. DOI: 10.1021/ol050523h) that an azide such as 11 is oxidized smoothly to the corresponding nitrile 12. This is an example of conversion from the alcohol to the acid oxidation state.

Several years ago, Teruaki Mukaiyama introduced the now commercially-available sulfinimidoyl chloride 14 as a reagent for converting ketone enolates to enones. Jun-ichi Matsuo of the Kitasato Institute, Kanagawa, has extended (Tetrahedron Lett. 2005, 46, 407. DOI: 10.1016/j.tetlet.2004.11.106) this oxidation to esters, thioesters, amides, lactams, and lactones such as 13.

For more than two decades, Sharpless asymmetric epoxidation of allylic alcohols has been the workhorse for enantioselective synthesis. Karl Anker Jørgensen of Aarhus University, Denmark, has devised (J. Am. Chem. Soc. 2005, 127, 6964. DOI: 10.1021/ja051808s) what appears to be a practical competitor, the enantioselective epoxidation of α,β-unsaturated aldehydes such as 18 using the proline-derived organocatalyst 19. The (E)-aldehyde 18 is easily prepared from the inexpensive butenediol (16).

D. F. Taber, Org. Chem. Highlights 2006, February 13.