Tandem catalysis versus one-pot catalysis: ensuring process orthogonality in the transformation of essential-oil phenylpropenoids into high-value products via olefin isomerization–metathesis

Abstract

Conversion of essential-oil allylbenzenes (phenylpropenoids) to high-value fine chemicals via isomerization–metathesis is reported. The target reaction sequence involves isomerization of ArCH₂CHCH₂1 into the corresponding conjugated olefins 2, and ensuing cross-metathesis with acrylates to generate ArCHCHCO₂R 3. The second-generation Hoveyda catalyst HII was chosen for the metathesis step. A range of lead candidates was assessed for the isomerization step, of which most active was the Grotjahn catalyst [CpRu(PN)(MeCN)]PF₆ ([4]PF₆; PN = 2-PⁱPr₂-4-^tBu-1-Me-imidazole). The following order of isomerization activity was determined, using the isomerization of estragole 1a to anethole 2a (Ar = p-MeOC₆H₄) as a probe reaction: [CpRu(PN)(MeCN)]PF₆ > RuHCl(CO)(PPh₃)₃ > Ru(Me-allyl)₂(COD) > Pd₂Br₂(P^tBu₃)₂ > RuHCl(PPh₃)₃ > RuCl₃(μ₂-C)(μ₂,κ¹-C,η⁶-Mes-H₂IMes)Ru(H)(H₂IMes) (the “Grubbs hydride”) > RuHCl(CO)(H₂IMes)(PCy₃) > RuHCl(CO)(IMes)(PCy₃) > RuHCl(CO)(PCy₃)₂. To maximize process efficiency, a systematic comparison of orthogonal tandem catalysis versus sequential catalyst addition was undertaken, using catalysts [4]PF₆ and HII. The impact of each process type on product selectivity and catalyst compatibility was assessed. Selectivity was undermined in tandem isomerization–metathesis by competing metathesis of 1. Sequential catalyst addition eliminated this problem. The isomerization catalyst [4]PF₆ adversely affected metathesis yields when equimolar with HII, an effect traced to the imidazole functionality in [4]PF₆. However, at the low catalyst loadings required for efficient isomerization (0.1 mol% [4]PF₆), negligible impact on metathesis yields was evident. The target cinnamates and ferrulates were obtained in quantitative yields by coupling these steps in a one-pot isomerization–metathesis protocol.