Investigations on enzyme catalytic promiscuity: The first attempts at a hydrolytic enzyme-promoted conjugate addition of nucleophiles to α,β-unsaturated sulfinyl acceptors

Looking for new examples of enzyme catalytic promiscuity, attempts were made to use hydrolytic enzymes as catalysts for a conjugate addition of nucleophiles toα,β-unsaturated sulfinyl derivatives. The addition of piperidine to phenyl vinyl sulfoxide in chloroform proceeded both in the enzyme-catalyzed and non-catalyzed process, while in the former case the reaction was 2.5-fold faster. On the contrary, the conjugate addition of benzenethiol to phenyl vinyl sulfoxide proceeded only in the presence of enzymes and when ethanol was used as solvent. In no case were the products enantiomerically enriched. However, the addition of benzenethiol to a better Michael acceptor, namely a cyclic α-sulfinylalkenylphosphonate, performed in the presence of various lipases under kinetic resolution conditions gave in certain instances both the product and the recovered substrate with up to 25% optical purity. Although the stereoselctivity and the rates of these reactions were quite low, this are the first examples of the lipase-catalyzed Michael addition of heteroatom nucleophiles to α,β-unsaturated heteroorganic acceptors. Some mechanistic considerations are presented.

Figure optionsDownload as PowerPoint slideHighlights
► The first example of lipase-catalyzed Michael addition to heteroorganic acceptors.
► Differences in binding of various Michael acceptors are indicated.
► The results pave the way for the application of enzyme catalytic promiscuity in heteroatom chemistry.