Asymmetric aldol reactions. Mechanism of solvent effect on stereoselectivity is specific, stoichiometric binding of tetrahydrofuran to a chiral titanium enolate

Solvent plays an important role in aldol reactions of an acyloxazolidinone-derived titanium enolate. Diethyl ether produces nearly fivefold higher diastereofacial selectivity than THF. We now show that this strong solvent effect arises from stoichiometric binding, most probably to the titanium, of THF in the transition structure, whereas ether is not bound. These mechanistic results indicate that THF lowers the selectivity by interfering with chelation control, which is highly preferred in ether. Implications include the possibility of using other ethers to improve chelation/nonchelation control still more, or even use of chiral ethers as chiral controller groups or adjuncts.