A Convenient Approach to C₂‐Chiral 1,1,4,4‐Tetrasubstituted Butanetetraols: Direct Alkylation or Arylation of Enantiomerically Pure Diethyl Tartrates

Abstract

C2‐Chiral 1,1,4,4‐tetraaryl‐ or 1,1,4,4‐tetraalkyl‐substituted butanetetraols have been conveniently synthesized via arylation or alkylation of unprotected diethyl (2R,3R)‐ and (2S,3S)‐tartrates with Grignard reagent. The chiral 1,1,4,4‐tetrasubstituted butanetetraols were characterized by IR, 1H‐ and 13C‐NMR, as well as LC/MS.

A computational, X-ray crystallographic and thermal stability analysis of TETROL and its pyridine and methylpyridine inclusion complexes

“…1,2 We were intrigued by the possibility that the closely related compound, (þ)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetrol 2 (TETROL) might show similar potential. Although TETROL is not a novel compound, 3 its use as an inclusion host compound has, to the best of our knowledge, not been reported previously.…”

“…Addition of the tartrate to the Grignard reaction was highly exothermic and thus this step was carried out with cooling in an ice-water bath. In a typical reaction, the use of bromobenzene (22.99 g, 146.5 mmol) and magnesium turnings (3.94 g, 162.0 mmol) in anhydrous THF, with (þ)-diethyl Ltartrate (5.00 g, 24.3 mmol), also in anhydrous THF, afforded a gum, which was crystallised and recrystallised from CH 2 Cl 2 /hexane/ MeOH to afford (þ)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetrol 2 as a white solid (4.68 g, 10.9 mmol, 45%), mp 147e149 C (lit., 3 …”

Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups

“…The hydroxy group composition of 1 ensures its diverse reactivity. In 2010, our group established a convenient access [ 18 ] to 1 via a direct alkylation of diethyl tartrates by using PhMgBr followed by further modifications involving highly regioselective 1,4-cycloetherization [ 19 ], 2,3-spiroboration [ 20 ], 2,3-sulfitation [ 21 ], and 2,3-methylation [ 22 ] of 1 . Therefore, the strategy for the catalyst’s preparation was based on the established regioselective 2,3-sulfitation reaction of 1 and ready hydrolysis of the corresponding sulfite ester 2 in NaOH solution to yield the chiral phosphoric acid 3 bearing two free hydroxy groups at the 2 and 3- positions, respectively, as shown in Scheme 1 .…”

“…Commercially available starting materials were used without further purification if not specified otherwise. Chiral phosphoric acid 3 was prepared according to a previous method [ 18 ].…”

Clathrates of TETROL: Further Aspects of the Selective Inclusion of Methylcyclohexanones in Their Energetically Unfavorable Axial Methyl Conformations

“…This compound was synthesized according to a published procedure. 1 This afforded a gum that was crystallized and recrystallized from CH 2 Cl 2 /hexane/MeOH to afford (+)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetrol 1 as a white solid (45%), mp 147−149°C (lit., 10 Preliminary structures were determined using the MMFF (Merck Pharmaceuticals) force field, followed by further geometry refinement at the DFT level using the B3LYP functional and progressively employing the 6-31G*, 6-311++G**, and 6-311++G(2df,2p) basis sets. Thermochemical calculations were carried out at the G3(MP2) and MP2/6-311++G(2df,2p) levels, with the former approach providing standard enthalpies of formation, and the latter, total Gibbs free energies at 298.15 K and 1 atm of pressure.…”