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Chiral Fluorinated α-Sulfonyl Carbanions: Enantioselective Synthesis and Electrophilic Capture, Racemization Dynamics, and Structure

Authors

  • Dr. Gunther Hellmann,

    1. Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen (Germany)
    2. Present address: DSM Nutritional Products Ltd. Wurmisweg 576, 4001 Kaiseraugst (Switzerland)
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  • Dr. Achim Hack,

    1. Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen (Germany)
    2. Present address: IMPAG AG, Feldeggstrasse 26, 8034 Zürich (Switzerland)
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  • Dr. Eric Thiemermann,

    1. Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen (Germany)
    2. Present address: F. Hoffmann - La Roche AG, Grenzacherstrasse 124, 4070 Basel (Switzerland)
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  • Dr. Olaf Luche,

    1. Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen (Germany)
    2. Present address: LISI Automotive Knipping, Verbindungstechnik GmbH, In der Helle 7, 58566 Kierspe (Germany)
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  • Prof. Dr. Gerhard Raabe,

    Corresponding author
    1. Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen (Germany)
    • Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen (Germany)
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  • Prof. Dr. Hans-Joachim Gais

    Corresponding author
    1. Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen (Germany)
    • Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen (Germany)
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Abstract

Enantiomerically pure triflones R1CH(R2)SO2CF3 have been synthesized starting from the corresponding chiral alcohols via thiols and trifluoromethylsulfanes. Key steps of the syntheses of the sulfanes are the photochemical trifluoromethylation of the thiols with CF3Hal (Hal=halide) or substitution of alkoxyphosphinediamines with CF3SSCF3. The deprotonation of RCH(Me)SO2CF3 (R=CH2Ph, iHex) with nBuLi with the formation of salts [RC(Me)[BOND]SO2CF3]Li and their electrophilic capture both occurred with high enantioselectivities. Displacement of the SO2CF3 group of (S)-MeOCH2C(Me)(CH2Ph)SO2CF3 (95 % ee) by an ethyl group through the reaction with AlEt3 gave alkane MeOCH2C(Me)(CH2Ph)Et of 96 % ee. Racemization of salts [R1C(R2)SO2CF3]Li follows first-order kinetics and is mainly an enthalpic process with small negative activation entropy as revealed by polarimetry and dynamic NMR (DNMR) spectroscopy. This is in accordance with a Cα[BOND]S bond rotation as the rate-determining step. Lithium α-(S)-trifluoromethyl- and α-(S)-nonafluorobutylsulfonyl carbanion salts have a much higher racemization barrier than the corresponding α-(S)-tert-butylsulfonyl carbanion salts. Whereas [PhCH2C(Me)SO2tBu]Li/DMPU (DMPU = dimethylpropylurea) has a half-life of racemization at −105 °C of 2.4 h, that of [PhCH2C(Me)SO2CF3]Li at −78 °C is 30 d. DNMR spectroscopy of amides (PhCH2)2NSO2CF3 and (PhCH2)N(Ph)SO2CF3 gave N[BOND]S rotational barriers that seem to be distinctly higher than those of nonfluorinated sulfonamides. NMR spectroscopy of [PhCH2C(Ph)SO2R]M (M=Li, K, NBu4; R=CF3, tBu) shows for both salts a confinement of the negative charge mainly to the Cα atom and a significant benzylic stabilization that is weaker in the trifluoromethylsulfonyl carbanion. According to crystal structure analyses, the carbanions of salts {[PhCH2C(Ph)SO2CF3]Li⋅L}2 (L=2 THF, tetramethylethylenediamine (TMEDA)) and [PhCH2C(Ph)SO2CF3]NBu4 have the typical chiral Cα[BOND]S conformation of α-sulfonyl carbanions, planar Cα atoms, and short Cα[BOND]S bonds. Ab initio calculations of [MeC(Ph)SO2tBu] and [MeC(Ph)SO2CF3] showed for the fluorinated carbanion stronger nC→σ*math image and nO→σ*math image interactions and a weaker benzylic stabilization. According to natural bond orbital (NBO) calculations of [R1C(R2)SO2R] (R=tBu, CF3) the nC→σ*S[BOND]R interaction is much stronger for R=CF3. Ab initio calculations gave for [MeC(Ph)SO2tBu]Li2 Me2O an O,Li,Cα contact ion pair (CIP) and for [MeC(Ph)SO2CF3]Li2 Me2O an O,Li,O CIP. According to cryoscopy, [PhCH2C(Ph)SO2CF3]Li, [iHexC(Me)SO2CF3]Li, and [PhCH2C(Ph)SO2CF3]NBu4 predominantly form monomers in tetrahydrofuran (THF) at −108 °C. The NMR spectroscopic data of salts [R1(R2)SO2R3]Li (R3=tBu, CF3) indicate that the dominating monomeric CIPs are devoid of Cα[BOND]Li bonds.

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