Titanium reagent discovery

Another issue important to the success of this chiral titanium reagent 31 was the discovery of a marked solvent effect. When the fumaric acid derivative is reacted with isoprene in the presence of 10 mol% of the titanium reagent 31 in toluene, poor optical purity results (36-68% ee). Interestingly the optical purity of the adduct greatly increased in the order benzene, toluene, xylenes, and mesitylene, with 92% ee obtained in the last. Mesitylene is difficult to remove, because of its high boiling point, and other solvents were screened in detail. As a result, the mixed solvent system toluene petroleum ether (1 1) was discovered to be very effective. 

The Orsay group found serendipitously that methyl p-tolyl sulfide was oxidized to methyl p-toly 1 sulfoxide with high enantiomeric purity (80-90% ee) when the Sharpless reagent was modified by addition of 1 mole equiv. of water [16,17]. The story of this discovery was described in a review [19], Sharpless conditions gave racemic sulfoxide and sulfone. Careful optimization of the stoichiometry of the titanium complex in the oxidation of p-tolyl sulfide led to the selection of Ti(0iPr)4/(7 ,7 )-DET/H20 (1 2 1) combination as the standard system [ 17]. In the beginning of their investigations, the standard conditions implied a stoichiometric amount of the chiral titanium complex with respect to the prochiral sulfide [16,17,20-23]. Later, proper conditions were found, which decreased the amount of the titanium complex without too much alteration of the enantioselectivity [24,25],... 

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