High-value alcohols and higher-oxidation-state compounds by catalytic Z-selective cross-metathesis

A ruthenium–disulfide catalyst is presented that is effective in generating compounds of medical and industrial utility (alcohols that contain a phenol, an aldehyde, or a carboxylic acid) by room-temperature, inexpensive, high-yielding cross-metathesis. A promising olefin metathesis catalyst Catalytic olefin metathesis is one of the most widely used reactions in synthetic organic chemistry, but its utility has been limited by the dearth of chemical transformations that directly generate acyclic Z allylic alcohols. In this manuscript, the authors present an electronically modified ruthenium-disulphide catalyst that is uniquely effective in generating compounds of medical and industrial utility (alcohols containing a phenol, an aldehyde or a carboxylic acid) by room-temperature, inexpensive, high-yielding cross-metathesis. The efficiency of the catalyst is demonstrated in the synthesis of naturally occurring antitumour agent neopeltolide and a single-step stereoselective gram-scale conversion of a renewable feedstock to an antifungal agent. Olefin metathesis catalysts provide access to molecules that are indispensable to physicians and researchers in the life sciences 1 , 2 . A persisting problem, however, is the dearth of chemical transformations that directly generate acyclic Z allylic alcohols, including products that contain a hindered neighbouring substituent or reactive functional units such as a phenol, an aldehyde, or a carboxylic acid. Here we present an electronically modified ruthenium–disulfide catalyst that is effective in generating such high-value compounds by cross-metathesis. The ruthenium complex is prepared from a commercially available precursor and an easily generated air-stable zinc catechothiolate. Transformations typically proceed with 5.0 mole per cent of the complex and an inexpensive reaction partner in 4–8 hours under ambient conditions; products are obtained in up to 80 per cent yield and 98:2 Z : E diastereoselectivity. The use of this catalyst is demonstrated in the synthesis of the naturally occurring anti-tumour agent neopeltolide and in a single-step stereoselective gram-scale conversion of a renewable feedstock (oleic acid) to an anti-fungal agent. In this conversion, the new catalyst promotes cross-metathesis more efficiently than the commonly used dichloro–ruthenium complexes, indicating that its utility may extend beyond Z -selective processes.