Design, Development,\nand Scale-Up of a Stereoselective\nSynthesis of (1<i>R</i>,3<i>R</i>)‑3-(3,5-Bis(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane\nCarboxylic Acid

This report describes the design, development, and scale-up\nof\na stereoselective synthesis of (1<i>R</i>,3<i>R</i>)-3-(3,5-bis(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane carboxylic\nacid (<b>1)</b>, a key intermediate toward the synthesis of\na promising developmental agrochemical. The synthesis features d-mannitol as a sustainable chiral pool starting material, a\ndouble Heck coupling reaction, and the invention of diastereoselective\ndichlorocyclopropanation. Details disclosed include the route design,\ndevelopment of enabling steps, and learnings from a kilogram-scale\ncampaign. The nine-step route was used to produce 1.5 kg of (1<i>R</i>,3<i>R</i>)-3-(3,5-bis(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane\ncarboxylic acid in 13% overall yield, 97.8% purity, and excellent\nenantiopurity (>99.5% <i>ee)</i>.