Ruthenium-catalysed multicomponent synthesis of the 1,3-dienyl-6-oxy polyketide motif

Polyketide natural products are an important class of biologically active compounds. Although substantial progress has been made on the synthesis of repetitive polyketide motifs through the iterative application of a single reaction type, synthetic access to more diverse motifs that require more than one type of carbon-carbon bond connection remains a challenge. Here we describe a catalytic, multicomponent method for the synthesis of the privileged polyketide 1,3-dienyl-6-oxy motif. The method allows for the formation of two new carbon-carbon bonds and two stereodefined olefins. It generates products that contain up to three contiguous sp(3) stereocentres with a high stereoselectivity in a single operation and can be used to generate chiral products. The successful development of this methodology relies on the remarkable efficiency of the ruthenium-catalysed alkene-alkyne coupling reaction between readily available vinyl boronic acids and alkynes to provide unsymmetrical 3-boryl-1,4-diene reagents. In the presence of carbonyl compounds, these reagents undergo highly diastereoselective allylations to afford the desired 1,3-dienyl-6-oxy motif and enable complex polyketide synthesis in a rapid and asymmetric fashion. A ruthenium-catalysed multicomponent reaction provides rapid and tunable access to 1,3-dienyl-6-oxy polyketide motifs. An initial alkene-alkyne coupling produces unsymmetrical 3-boryl-1,4-dienes. Allylation of aldehydes and ketones with these products is highly diastereoselective and results in the formation of two carbon-carbon bonds, two stereodefined olefins and up to three contiguous sp(3) stereocentres.