Kaitlyn C. Gray, P. Heider, Patrick T. Mcgough
Jul 1, 2019
Citations
0
Influential Citations
8
Citations
Journal
Organic Process Research & Development
Abstract
Optimization of the thiol–ene reaction for the preparation of methyl 3-((3,3,3-trifluoropropyl)thio)propanoate (4), a key intermediate in the synthesis of the sap-feeding insecticidal candidate tyclopyrazoflor (1), is described. The major challenge with the radical thiol–ene chemistry was control of the regioselectivity between the linear and branched products. Reducing the radical initiation temperature was found to be the key variable in controlling the selectivity. Because of the high cost and storage challenges associated with the use of the room-temperature diazo initiator 2,2′-azobis(4-methoxy-2,4-dimethylvaleronitrile) (V-70), a two-component initiator system consisting of benzoyl peroxide and N,N-dimethylaniline was developed, allowing for radical initiation at temperatures as low as −15 °C. Application of semibatch operation gave 90:1 selectivity favoring the linear product. The overall yield and selectivity of the radical thiol–ene reaction were improved from 78% yield and 11:1 selectivity with ...