Computational and Experimental Study of Turbo‐Organomagnesium Amide Reagents: Cubane Aggregates as Reactive Intermediates in Pummerer Coupling

Abstract The dynamic equilibria of organomagnesium reagents are known to be very complex, and the relative reactivity of their components is poorly understood. Herein, a combination of DFT calculations and kinetic experiments is employed to investigate the detailed reaction mechanism of the Pummerer coupling between sulfoxides and turbo‐organomagnesium amides. Among the various aggregates studied, unprecedented heterometallic open cubane structures are demonstrated to yield favorable barriers through a concerted anion‐anion coupling/ S−O cleavage step. Beyond a structural curiosity, these results introduce open cubane organometallics as key reactive intermediates in turbo‐organomagnesium amide mixtures.


Calculated aggregates formed from the Grignard reagent and the magnesium amide
. Reaction free energies (in kcal/mol) of calculated aggregates formed from the Grignard reagent and the magnesium amide.  The spectroscopic data was found consistent with the literature. 6

Signal stability on No-D 1 H-NMR experiments
To make sure that the reaction can be monitored without internal reference, the signal stability was assessed in No-D 1 H-NMR experiments over a long time period (8 h) using absolute integration numbers. Whenever possible, avoiding an internal standard on reactions with highly reactive intermediates removes potential interferences caused by degradation of the internal standard in solution, and improves the signal-to-noise ratio and shimming compared to NMR tube inserts.
A solution of 1,1,2,2-tetrachloroethane (TCE, 5.0 µL, 0.05 mmol) in THF (0.5 mL) was used to determine the signal stability of the NMR measurements under the experimental conditions. Consecutive No-D 1 H-NMR spectra were recorded over a time period of 8 h every 240 s. The absolute integral of the TCE in the first scan was assigned to its initial known concentration (0.1 M) and used to reference the integral values in the subsequent measurements ( Figure S1). Expectedly, the signal oscillated stochastically over time around the expected value with a maximum relative error of 2.6% of the expected value (Table S1).  Table S1: Summary of the signal stability measurements.

Monitoring time (h) 8
Measurements 120 [ The procedure was adapted from the original report by Mendoza and co-workers. 8 NMR experiments were performed in oven-dried, Ar-flushed NMR tubes equipped with a septum. Solutions were transferred using gas tight syringes that were flushed with inert gas prior to use. The appropriate sulfoxide 7 (0.05 mmol) was weighed into the NMR tube, the atmosphere exchanged to Ar followed by the addition of dry THF. The mixture was cooled down to 0 °C with an ice bath and base 4a (1.1 equiv.) was added. The solution was allowed to warm up to r.t. at which point the spectrometer was shimmed and tuned to the sample, i-PrMgCl (1e, 2.0 M in THF, 1.05 equiv.) was added in one shot. The evolution of the system was monitored with consecutive 1 H-NMR experiments at 25 °C.

S2-9
Kinetic profiling of the conversion of 7a to 8a followed by 1
a Note: The broad signals denoted as S1 are likely an average of various starting material complexes in fast equilibrium in solution. The inherent stability of this mixture prevented further structural characterization by NMR.  (a) S1 S1 8a 8a S1 S2- 11   Table S2. Data of the conversion of S1 with time (see Figure S4)
a Note: The broad signals denoted as S1-d3 are likely an average of various starting material complexes in fast equilibrium in solution. The inherent stability of this mixture prevented further structural characterization by NMR.   Table S3).