Spectroscopic and X-ray Crystallographic Evidence for Electrostatic Effects in 4-Substituted Cyclohexanone-Derived Hydrazones, Imines, and Corresponding Salts

Abstract

The axial conformer of several 4-substituted cyclohexanone hydrazone salts was found to predominate in solution. Changes in the charge of the molecule and the polarity of the solvent led to changes in the conformational preference of each molecule that was consistent with electrostatic stabilization of the axial conformer. 1 H NMR spectroscopic analysis was utilized to determine the structure of cyclohexanone-derived substrates by comparison to conformationally restricted transdecalone derivatives and computational models. X-ray crystallography demonstrated that the axial configuration of a pendant benzyloxy group is the preferred conformation of an iminium ion in the solid state. The structure of a neutral hydrazone was also determined to favor the axial configuration for a pendant benzyloxy group in the solid state.

A Catalytic Enantioselective Tandem Allylation Strategy for Rapid Terpene Construction: Application to the Synthesis of Pumilaside Aglycon

“…While this preference is indeed surprising, it is in line with observations about the axial preference of C4 alkoxy groups in cyclohexanone derivatives . This feature is thought to arise from either (a) electrostatic attraction between the axial oxygen that bears a δ- and either the carbonyl carbon or axial hydrogens α to the carbonyl, both of which bear δ+; (b) hydrogen bonding between the axial C4 heteroatom and acidic axial hydrogens adjacent to the carbonyl; or (c) hyperconjugative interactions between the C–O σ* and an adjacent axial CH donor . In the context of this tandem reaction sequence, 1,4- syn selectivity is highest with geranial-derived substrates (i.e., Scheme and entries 7–9 in Table ) suggesting that the axial preference for an OB(pin), acting in concert with a preference for the larger R 2 to reside in an equatorial site, enhances selectivity for reaction through structure A .…”

Fluorine‐Directed β‐Galactosylation: Chemical Glycosylation Development by Molecular Editing

“…The importance of electrostatic interactions from ancillary groups on the conformational equilibria of substituted oxocarbenium ions, and the diastereoselectivities of their reactions, is exemplified by the elegant work of Woerpel and co-workers. [26,27] In addition to this ground state analysis, it is also conceivable that the transition state topology would be consistent with the Anh-Eisenstein 1,2-induction model, [28] such that orbital overlap is maximised when the s CÀF * orbital antiperiplanar to the approach trajectory of the nucleophile. This may account for the consistent formation of 1,2-trans glycosides.…”

Oxidation of Secondary Methyl Ethers to Ketones

“…(24). 25,26 Magnesium sulfate (361 mg, 3.0 mmol, 2.0 equiv) was added to a solution of ketone 25 (192 mg, 1.5 mmol, 1.0 equiv), ethylene glycol (0.3 mL, 5.3 mmol, 3.5 equiv) and a catalytic amount of p-toluenesulfonic acid (26 mg, 0.15 mmol, 10 mol%) in toluene (5 mL). The resulting mixture was refluxed for 4 h. The reaction was cooled to 20 °C and quenched with saturated aqueous sodium bicarbonate (10 mL).…”