Chiral fluorinated α-sulfonyl carbanions: Enantioselective synthesis and electrophilic capture, racemization dynamics, and structure

  • Hellmann G
  • Hack A
  • Thiemermann E
 et al. 
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Abstract

Enantiomerically pure triflones R(1) CH(R(2) )SO2 CF3 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 CF3 Hal (Hal=halide) or substitution of alkoxyphosphinediamines with CF3 SSCF3 . The deprotonation of RCH(Me)SO2 CF3 (R=CH2 Ph, iHex) with nBuLi with the formation of salts [RC(Me)SO2 CF3 ]Li and their electrophilic capture both occurred with high enantioselectivities. Displacement of the SO2 CF3 group of (S)-MeOCH2 C(Me)(CH2 Ph)SO2 CF3 (95 % ee) by an ethyl group through the reaction with AlEt3 gave alkane MeOCH2 C(Me)(CH2 Ph)Et of 96 % ee. Racemization of salts [R(1) C(R(2) )SO2 CF3 ]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 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 [PhCH2 C(Me)SO2 tBu]Li/DMPU (DMPU = dimethylpropylurea) has a half-life of racemization at -105 °C of 2.4 h, that of [PhCH2 C(Me)SO2 CF3 ]Li at -78 °C is 30 d. DNMR spectroscopy of amides (PhCH2 )2 NSO2 CF3 and (PhCH2 )N(Ph)SO2 CF3 gave NS rotational barriers that seem to be distinctly higher than those of nonfluorinated sulfonamides. NMR spectroscopy of [PhCH2 C(Ph)SO2 R]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 {[PhCH2 C(Ph)SO2 CF3 ]Li⋅L}2 (L=2 THF, tetramethylethylenediamine (TMEDA)) and [PhCH2 C(Ph)SO2 CF3 ]NBu4 have the typical chiral Cα S conformation of α-sulfonyl carbanions, planar Cα atoms, and short Cα S bonds. Ab initio calculations of [MeC(Ph)SO2 tBu](-) and [MeC(Ph)SO2 CF3 ](-) showed for the fluorinated carbanion stronger nC →σ* SCF 3 and nO →σ* SCF 3 interactions and a weaker benzylic stabilization. According to natural bond orbital (NBO) calculations of [R(1) C(R(2) )SO2 R](-) (R=tBu, CF3 ) the nC →σ*SR interaction is much stronger for R=CF3 . Ab initio calculations gave for [MeC(Ph)SO2 tBu]Li⋅2 Me2 O an O,Li,Cα contact ion pair (CIP) and for [MeC(Ph)SO2 CF3 ]Li⋅2 Me2 O an O,Li,O CIP. According to cryoscopy, [PhCH2 C(Ph)SO2 CF3 ]Li, [iHexC(Me)SO2 CF3 ]Li, and [PhCH2 C(Ph)SO2 CF3 ]NBu4 predominantly form monomers in tetrahydrofuran (THF) at -108 °C. The NMR spectroscopic data of salts [R(1) (R(2) )SO2 R(3) ]Li (R(3) =tBu, CF3 ) indicate that the dominating monomeric CIPs are devoid of Cα Li bonds.

Author-supplied keywords

  • ab initio calculations
  • carbanions
  • chirality
  • racemization
  • sulfone

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Authors

  • Gunther Hellmann

  • Achim Hack

  • Eric Thiemermann

  • Olaf Luche

  • Gerhard Raabe

  • Hans Joachim Gais

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