Substoichiometric TiCl4-mediated vicinal difunctionalization of α,β-acetylenic ketones for the synthesis of β-halo Baylis-Hillman olefins

A substoichiometric amount of titanium tetrachloride was found to be effective to promote and participate in the tandem alpha -hydroxyalkylation/beta -chlorination of alpha,beta -acetylenic ketones in the presence of (n-Bu)(4)NI. This method provides the concise synthesis of (E)-beta -halo Baylis-Hillman adducts. No beta -iodo products were detected when using this combination of halogen sources. The reaction process involves 1,4-addition of chloro anion released from TiCl4 onto alpha,beta -acetylenic ketones to give TiCl3-allenolate intermediates followed by the titanium Lewis acid-promoted carbonyl addition. Modest to good yields (53-77%) and excellent E/Z stereoselectivity (>95%) have been obtained for 10 examples. (C) 2001 Elsevier Science Ltd. All rights reserved.