Development of phosphinic Brønsted acids for applications in asymmetric catalysis Emily Griffiths , Ryan Mewis, Beatrice Macia-Ruiz, Vittorio Caprio, Andrew Caffyn Manchester Metropolitan University, UK 1,1’-binaphthalene-2,2’-diol (BINOL) phosphine-based Brønsted acids are important acid catalysts. BINOL- derived chiral phosphoric acids are useful organocatalysts for a range of transformations e.g. reductive aminations, Diels–Alder and cascade reactions. Excellent enantioselectivities are readily obtainable. The Brønsted acid strength dictates the success of these ligands and thus has a direct effect on the catalytic potential of these acids. The strength of a Brønsted acid can be significantly increased by the presence of fluorine atoms near the acidic site. This work is focused on the production of a fluorinated Brønsted acid which is phosphinic based. It is hypothesised that the increased acidity will yield higher conversions whilst retaining enantioselectivity. We have synthesised the fluorinated acid and its pK a was determined to be significantly more acidic than the parent Bronsted acid (pK a of 8.44 vs 3.37 – the former is RR’(CF 2 ) 2 PO(OH) whereas the latter is RR’O 2 PO(OH)). The fluorinated phosphinic acid was synthesised through a seven-step synthesis from BINOL. The overall yield for the synthesis was 60%. The synthetic steps can be reduced from seven to five by treatment of 1,1’-binaphthalene- 2,2’-dimethyl to the corresponding phosphonate ester. This circumvents two synthetic steps, thus shortening the synthetic procedure considerably and increasing the throughput to latter reactions. We showcase this synthetic transformation as part of our presentation. The pK a of the fluorinated Brønsted acid was determined through the use of titrimetric 19 F NMR spectroscopy. The approach is based on that reported by Jeannerat et. al. 1 Two sulfonyl amide compounds (of the type PhSO 2 NHSO 2 (C 5 F 5 )) were used as reference standards which differed in the position of the nitro group on the non-fluorinated aromatic ring (4-NO 2 = 1 and 3-NO 2 = 2 ). The pK a determined through employment of each reference compound was 8.33 for 1 and 8.54 for 2 . The approach was validated by independently validating the pK a ’s of the two reference compounds and comparing against reported literature values. These were determined to be 6.61 for 1 (literature pK a = 6.60) and 6.72 for 2 (literature pK a = 6.73). To assess the catalytic potential of the fluorinated Brønsted acid prepared, a Friedel-Crafts reaction has been considered. The parent non-fluorinated Brønsted acid has been used as a control as well as other Brønsted acids bearing, for example, 2,4,6-triisopropylphenyl (TRIP) groups. These Brønsted acids have a range of pK a values and therefore comparison of product yields under the same conditions enable the direct affect of pK a on yield to be shown. References 1. R. Shivapurkar and D. Jeannerat, Analytical Methods , 2011, 3 , 1316-1322
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