Amine and Titanium (IV) Chloride, Boron (III) Chloride or Zirconium (IV) Chloride-Promoted Baylis-Hillman Reactions

Abstract

The Baylis-Hillman reactions of various aryl aldehydes with methyl vinyl ketone at temperatures below -20oC using Lewis acids such as titanium (IV) chloride, boron (III) chloride or zirconium (IV) chloride in the presence of a catalytic amount of selected amines used as a Lewis bases afford the chlorinated compounds 1 as the major product in very high yields. Acrylonitrile can also undergo the same reaction to give the corresponding chlorinated product in moderate yield. A plausible reaction mechanism is proposed. However, if the reaction was carried out at room temperature (ca. 20oC), then the Z-configuration of the elimination product 3, derived from 1, was formed as the major product.

Recent Advances in the Baylis−Hillman Reaction and Applications

“…Shi and co-workers , examined similar TiCl 4 -mediated coupling of activated alkenes with various aldehydes in the presence of various Lewis bases such as amines (DBU, Et 3 N, and Et 2 NH), quaternary ammonium salt (TBAB), chalcogenides (Me 2 S), oxycompounds (alcohols, ethers, and ketones) (Scheme ). In the case of oxycompounds, they also studied the applicability of enantiopure oxycompounds 112 − 115 (Figure ); however, the products were obtained in poor enantioselectivities.…”

“…In these cases the usual Baylis-Hillman adducts were not obtained; instead, we obtained an interesting class of functionalized fused furans (eqs 58 and 59). 223 Li and co-workers [224][225][226] reported the reaction between R,β-acetylenic ketones and aromatic aldehydes in the presence of TiCl 4 or TiBr 4 to provide the desired β-halo Baylis-Hillman adducts (Scheme Shi and co-workers 227,228 examined similar TiCl 4mediated coupling of activated alkenes with various aldehydes in the presence of various Lewis bases such as amines (DBU, Et 3 N, and Et 2 NH), 229 quaternary ammonium salt (TBAB), 230 chalcogenides (Me 2 S), 231 oxycompounds (alcohols, ethers, and ketones) 232 (Scheme 63). In the case of oxycompounds, they also studied the applicability of enantiopure oxycompounds 112-115 (Figure 14); however, the products were obtained in poor enantioselectivities.…”

Acrylamide in the Baylis−Hillman Reaction: Expanded Reaction Scope and the Unexpected Superiority of DABCO over More Basic Tertiary Amine Catalysts

“…Although this process furnishes densely functionalized products amenable to further structural elaboration from relatively simple starting materials, it suffers from low reaction rates and limited substrate scope. Early efforts to accelerate the Baylis−Hillman reaction relied on physical methods (i.e., high pressures or microwave radiation),2e whereas more convenient strategies based on the use of strongly nucleophilic catalysts, protic solvents, , ionic additives, , and Lewis acid catalysts have been reported recently. Despite these advances, a number of α,β-unsaturated substrates of low electrophilicity remain somewhat reluctant coupling partners in this reaction.…”

Titanium Enolate Chemistry at the Beginning of the 21st Century

“…Shi and Feng116 proposed a detailed mechanism to explain the transformations shown in Scheme . Li et al128a obtained products of type 89 in the presence of TiCl 4 and ( n Bu) 4 NI.…”