In straitened circumstances: In an asymmetric version of the acid‐catalyzed acetalization of aldehydes, a novel member of the chiral confined Brønsted acid family significantly outperformed previously established catalysts, providing cyclic acetals with excellent enantioselectivity (see scheme; Ar=2‐iPr‐5‐MeC6H3).

A highly enantioselective kinetic resolution of diols via asymmetric acetalization has been achieved using a chiral confined imidodiphosphoric acid catalyst. The reaction is highly efficient for the resolution of tertiary alcohols, giving selectivity factors of up to >300. Remarkably, even in cases where the selectivity factors are only moderate, highly enantioenriched diols are obtained via a stereodivergent resolution to diastereomeric acetals.

Beengte Verhältnisse: Eine asymmetrische Version der säurekatalysierten Acetalisierung von Aldehyden wird vorgestellt. Ein neues Mitglied der beengten chiralen Brønsted‐Säuren zeigte eine deutlich bessere Leistungsfähigkeit als bisher bekannte Katalysatoren und ergab cyclische Acetale mit ausgezeichneter Enantioselektivität (siehe Schema; Ar=2‐iPr‐5‐MeC6H3).

Bridging the gap: Brønsted acids catalyze an intramolecular SN2‐type alkylation of alcohols with ethers by bridging a pentacoordinate transition state, thus simultaneously activating both the leaving group and nucleophile (see scheme). Density functional calculations provide detailed insight into the course of the reaction and the transition‐state structure.

Unless otherwise stated, all reagents were purchased from commercial suppliers and used without further purification. All solvents used in the reactions were distilled from appropriate drying agents prior to use. Reactions were monitored by thin layer chromatography on silica gel precoated plastic sheets (0.2 mm, Machery-Nagel). Visualization was accomplished by irradiation with UV light at 254 nm and/or phosphomolybdic acid (PMA) stain. Column chromatography was performed on Merck silica gel (60, particle size 0.040-0.063 mm). Proton and carbon NMR spectra were recorded on Bruker AV-500 or Bruker AV-400 spectrometer in deuterated solvent. Proton chemical shifts are reported in ppm (δ) relative to tetramethylsilane (TMS) with the solvent resonance employed as the internal standard (C 6 D 6 , δ 7.16 ppm; DMSO-d 6 , δ 2.49 ppm; CDCl 3 δ 7.24). Data are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t= triplet, q = quartet, m = multiplet), coupling constants (Hz) and integration. 13 C chemical shifts are reported in ppm from tetramethylsilane (TMS) with the solvent resonance as the internal standard (C 6 D 6 , δ 128.06 ppm; DMSO-d 6 , δ 39.5 ppm; CDCl 3 , δ 77.0). High resolution mass spectra were determined on a Bruker APEX III FTMS (7 T magnet). The enantiomeric ratios were determined by HPLC analysis employing a chiral stationary phase column specified in the individual experiment, by comparing the samples with the appropriate racemic mixtures. 15.5. HRMS (ESI+) m/z calculated for C 16 H 17 BrNaO 2 (M+Na) 343.0304, found 343.0303.General procedure for S3 and S4 [1] Palladium(II) chloride (10 mol%) was added to the solution of S1 in the corresponding alcohol (5 ml/mmol) under argon. The resulting suspension was heated to 80 ºC and stirred for 21-23 h until TLC showed full conversion. The reaction mixture was then concentrated and the product was purified by column chromatography on silica gel using EtOAc/hexane as the eluent.

The Catalytic Asymmetric Acetalization. -The first catalytic asymmetric acetalization of aldehydes is developed. The use of the novel Broensted acid, which is readily available from natural thymol, provides acetals with excellent enantioselectivity and outperforms known catalysts. -(KIM, J. H.; CORIC, I.; VELLALATH, S.; LIST*, B.; Angew. Chem., Int. Ed. 52 (2013) 16, 4474-4477, http://dx.

A catalytic enantioselective thioacetalization reaction has been developed. Various aldehydes react with unsymmetrical 1,3- or 1,2-dithiols to furnish chiral, enantioenriched thioacetals in excellent enantioselectivities upon treatment with a nitrated imidodiphosphoric acid catalyst. The transformation is assumed to proceed via a thionium ion intermediate

Resolution of Diols via Catalytic Asymmetric Acetalization. -Optically active imidodiphosphoric acid catalysts (I) are used in the title reactions with tertiary alcohols. The desired acetals and the remaining diol enantiomer are obtained with generally high e.e. values and in most cases with excellent diastereoselectivity. In a few cases, where the selectivity factors are only moderate, highly enantioenriched diols are available via stereodivergent resolution to diastereomeric acetals followed by deprotection. -(KIM, J. H.; CORIC, I.; PALUMBO, C.; LIST*, B.; J. Am. Chem. Soc. 137 (2015) 5, 1778-1781, http://dx.doi.org/10.1021/ja512481d ; MPI Kohlenforsch., D-45470 Muelheim/Ruhr, Germany; Eng.) -Lehmann 29-102