pK_a Values of Chiral Brønsted Acid Catalysts: Phosphoric Acids/Amides, Sulfonyl/Sulfuryl Imides, and Perfluorinated TADDOLs (TEFDDOLs)

Abstract

Measure what is measurable, and make measurable what is not so! This timeless quotation by Galileo forms the basis of all quantitative understanding, including asymmetric organocatalysis. We report pKa values for 15 chiral Brønsted acid catalysts in DMSO solutions (see scheme): the strongest acids were bis‐sulfonyl/sulfuryl imides (pKa=1.7–1.9) followed by phosphoric acids/amides (pKa=2.4–4.2). A new class of chiral Brønsted acids, tetrakis‐perfluoroalkyl analogues of TADDOLs (TEFDDOLs) have pKas from 2.4 to 5.7.

TEFDDOLs (α,α,α′,α′-Tetrakis(perfluoroaryl/alkyl)-2,2′-dimethyl-1,3-dioxolane-4,5-dimethanols): Highly Fluorinated Chiral H-Bond Donors and Brønsted Acids with Distinct H-Bonding Patterns and Supramolecular Architectures

“…9 A recent study of ours established accelerations (of epoxidation) up to 100.000-fold, relative to conventional solvents such as 1,4-dioxane. pK avalues for the TEFDDOLs 5a, 5b and 5f have been reported from this laboratory earlier, 11 revealing inter alia the remarkably high acidity of the "parent" tetrakis-CF 3 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 (DMSO) = 5.7], and in particular of its C 2 F 5 -homologue 5b [pK a (DMSO) = 2.4]. In analogy to the TADDOLs, we dubbed the α,α,α',α'-tetrakis(perfluoroalkyl/ aryl)-2,2-dimethyl-1,3-dioxolane-4,5-dimethanols 5 "TEFDDOLs".…”

“…11 It was found that the tetrakis-perfluoralkyl-TEFDDOLs 5a and 5b are rather acidic [pK a (5a) = 5.7; pK a (5b) = 2.4], wheras the tetrakispentafluorophenyl-TEFDDOL 5f has a pK a value of ca. 11 It was found that the tetrakis-perfluoralkyl-TEFDDOLs 5a and 5b are rather acidic [pK a (5a) = 5.7; pK a (5b) = 2.4], wheras the tetrakispentafluorophenyl-TEFDDOL 5f has a pK a value of ca.…”

Chiral Brønsted acid-catalyzed enantioselective ionic [2+4] cycloadditions

“…15 Insignificant stereoinduction is expected for the separated ion pairs, which is consistent with the observation that the reactions catalyzed by 16 and 18 in acetonitrile produced racemic products (entries 2 and 4). The higher catalytic activity of 18 in toluene and dioxane could be attributed to a higher acidity of this compound relative to the other catalysts 16 as well as to a lower coordinating ability of the resultant anion. A stronger Brønsted acid is expected to populate larger quantities of the oxocarbenium ion, while an ion pair (6) with a less coordinating anion will be more reactive due to the lower energy of the LUMO.…”

Chemoenzymatic Synthesis of Each Enantiomer of Orthogonally Protected 4,4-Difluoroglutamic Acid: A Candidate Monomer for Chiral Brønsted Acid Peptide-Based Catalysts

“…vii The most successful non-enzymatic Brønsted acid catalysts reported to date appear to exhibit p K a values that are lower than typical aspartic or glutamic acid residues. viii Therefore, we wondered if 4,4-difluoroglutamic acid, by virtue of the inductive effect of the fluorine atoms, ix could provide a boost in catalytic activity for Brønsted acid catalyzed processes, over its proteinogenic glutamic counterpart. Such a residue then might be inserted into peptide libraries, facilitating the search for new chiral Brønsted acid catalysts (Figure 1b).…”