The Resolution of Racemic Alcohols through the Half-Acid Oxalate Esters.

A New Synthesis of Optically active Myo-Inositol 1- Phosphates, Tetrahedron Letters (50) 4791-4794, 1971 is as far as I can see the only paper teaching any use of acid oxalate esters.  This is surprising since the introduction is so simple, the addition to the molecular weight is small as derivatization goes, and the reverse of the reaction can be done by oxidation under neutral conditions to complement acid or basic hydrolyses that can lead to rearrangement for some substrates.  The use of the oxalyl chloride reagent has become routine in the laboratory since this paper was published for the preparation of acid chlorides. What is not touched upon in this paper but is the main attraction for the KiloMentor is the potential for these half-ester half acids to be extracted into an aqueous phase as their salts, thus achieving phase-switching purification of an alcohol.  Mention is made in the paper that upon recrystallization some of the oxalate group is lost with the regeneration of the starting alcohol but this should not be a problem if the derivative is only intended to provide a temporary handle for phase-switching of the salt. It seems from the example that these derivatives can be prepared from even quite hindered secondary alcohols and the alcohol recovered without loss of stereochemistry.

The procedure provided for making the half oxalate reports treatment of DL-1,2,4,5,6-penta-O-acetyl-myoinositol (I), which has one free hydroxyl, with a 5-fold excess of oxalyl chloride in pyridine-chloroform at -10 C and subsequent hydrolysis (dilution with water) to give the acid oxalate (II) in 83% yield, m.p. 191-193 C (with decomposition; from CHCl₃-ether)

The decarboxylation that restored the alcohol functionality without rearrangement of the acetate esters was done by oxidizing “with lead tetraacetate in the presence of cupric acetate in pyridine/dioxane under argon (30 C, 5 hr)…”

Oxidizing with lead tetraacetate on-scale is regarded as troublesome; however, a  non-aqueous work-up which  destroys any excess Pb(IV) by reducing it with oxalic acid (which is oxidized to carbon dioxide) and then adding further oxalic acid to precipitate lead (II) oxalate (water solubility 0.65 mg/ 100 ml of water) which is then filtered should work well. 

Other half esters that can serve the same phase-shifting purpose are phthalate, succinate, and maleate; however, these cannot be removed by oxidation.