Duangdee, Nongnaphat Harnying, Wacharee Rulli, Giuseppe Neudörfl, Jörg-M. Gröger, Harald Berkessel, Albrecht Highly Enantioselective Organocatalytic Trifluoromethyl Carbinol SynthesisA Caveat on Reaction Times and Product Isolation Aldol reactions with trifluoroacetophenones as acceptors yield chiral α-aryl, α-trifluoromethyl tertiary alcohols, valuable intermediates in organic synthesis. Of the various organocatalysts examined, Singh’s catalyst [(2<i>S</i>)-<i>N</i>-[(1<i>S</i>)-1-hydroxydiphenylmethyl-3-methylbutyl]-2-pyrrolidinecarbox­amide] was found to efficiently promote this organocatalytic transformation in a highly enantioselective manner. Detailed reaction monitoring (<sup>19</sup>F-NMR, HPLC) showed that, up to full conversion, the catalytic transformation proceeds under kinetic control and affords up to 95% ee in a time-independent manner. At longer reaction times, the catalyst effects racemization. For the product aldols, even weak acids (such as ammonium chloride) or protic solvents, can induce racemization, too. Thus, acid-free workup, at carefully chosen reaction time, is crucial for the isolation of the aldols in high (and stable) enantiomeric purity. As evidenced by <sup>19</sup>F-NMR, X-ray structural analysis, and independent synthesis of a stable intramolecular variant, Singh’s catalyst reversibly forms a catalytically inactive (“parasitic”) intermediate, namely a <i>N</i>,<i>O</i>-hemiacetal with trifluoroacetophenones. X-ray crystallography also allowed the determination of the product aldols’ absolute configuration (<i>S</i>). intramolecular variant;reaction time;organocatalytic transformation;Reaction Times;protic solvents;transformation proceeds;catalyst effects racemization;product aldols;Product IsolationAldol reactions;enantioselective manner;synthesis;HPLC;Singh;trifluoroacetophenone;ammonium chloride;enantiomeric purity;reaction times 2012-07-11
    https://acs.figshare.com/articles/dataset/Highly_Enantioselective_Organocatalytic_Trifluoromethyl_Carbinol_Synthesis_A_Caveat_on_Reaction_Times_and_Product_Isolation/2505802
10.1021/ja302511t.s003