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

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 Zallylic 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 dichlororuthenium complexes, indicating that its utility may extend beyond Z-selective processes.
In 2009, it was demonstrated that a molybdenum (Mo) monopyrrolide aryloxide complex can promote ring-opening/cross-metathesis with high Z selectivity (3). This initial discovery and the attendant stereochemical model paved the [...]