A Simple and Broadly Applicable C-N Bond Forming Dearomatization Protocol Enabled by Bifunctional Amino Reagents.

Xiaofeng Ma,Tom A Young,Joshua J Farndon,John F Bower,Natalie Fey

doi:10.1002/anie.201708176

Xiaofeng Ma, Tom A Young + Show 3 more

Open Access

https://doi.org/10.1002/anie.201708176

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Abstract

A C−N bond forming dearomatization protocol with broad scope is outlined. Specifically, bifunctional amino reagents are used for sequential nucleophilic and electrophilic C−N bond formations, with the latter effecting the key dearomatization step. Using this approach, γ‐arylated alcohols are converted to a wide range of differentially protected spirocyclic pyrrolidines in just two or three steps.

Highlights

Note that the calculations reported did not test the viability of an SET mechanism
Further multireference ab initio calculations would need to be performed to investigate the possibility of an SET mechanism, but these are outside the scope of the current study
(1) The reactant arene is assumed to be deprotonated, and to be sufficiently stable to exist as the free ion in solution

Summary

General experimental details

All materials were purchased from commercial sources (Acros, Aldrich, Alfa Aesar, Fluorochem and Strem) and used without any further treatment. Anhydrous solvents were obtained by distillation using standard procedures or by passage through drying columns supplied by Anhydrous Engineering Ltd. High-boiling solvents were removed from the reaction crudes employing rotary evaporators connected with high-vacuum pumps. Flash column chromatography (FCC) was performed using silica gel (Aldrich 40-63 μm, 230-400 mesh). Thin layer chromatography was performed using aluminium backed 60F254 silica plates. Infrared spectra were recorded in the range 4000-600 cm-1 on a Perkin Elmer Spectrum Two FTIR spectrometer as thin films or solids compressed on a diamond plate. Enantiomeric excess was determined by integration of chromatograms peaks. Chiral SFC was performed on an Agilent 1260 Infinity SFC Control Module system equipped with a quaternary pump, diode array detector and column thermostat under the conditions specified

Experimental procedures and data

Control experiments

Computational methods

Findings

Discussion