Recent years have witnessed unprecedented advances in the development of fast multidimensional NMR acquisition techniques. This progress could open valuable new opportunities for the elucidation of chemical and biochemical processes. This study demonstrates one such capability, with the first real-time Two-dimensional (2D) dynamic analysis of a complex organic reaction relying on unlabeled substrates. Implementing such measurements required the development of new ultrafast 2D methods, capable of monitoring multiple spectral regions of interest as the reaction progressed. The alternate application of these acquisitions in an interleaved, excitation-optimized fashion, allowed us to extract new structural and dynamic insight concerning the reaction between aliphatic ketones and triflic anhydride in the presence of nitriles to yield alkylpyrimidines. Up to 2500 2D NMR data sets were thus collected over the course of this nearly 100 min long reaction, in an approach resembling that used in functional magnetic resonance imaging. With the aid of these new frequency-selective low-gradient strength experiments, supplemented by chemical shift calculations of the spectral coordinates observed in the 2D heteronuclear correlations, previously postulated intermediates involved in the alkylpyrimidine formation process could be confirmed, and hitherto undetected ones were revealed. The potential and limitations of the resulting methods are discussed.
Multidimensional nuclear magnetic resonance plays a number of essential roles in present day spectroscopy. It is also an integral part of the image formation protocol in magnetic resonance imaging (MRI).[1] Traditional two-dimensional experiments are intrinsically time consuming, because many t 1 increments have to be acquired to obtain twodimensional spectra with adequate digital resolution in the indirect dimension.[2] Proposals for accelerating multidimensional NMR spectroscopy include non-Fourier transform schemes, [3] the acquisition of multiple NMR spectra in a single experiment, [4] and "single scan" multidimensional NMR spectroscopy, also called ultrafast NMR spectroscopy (UF NMR), have been introduced. The latter methodology was inspired by echo planar imaging (EPI) [5] and was developed by Frydman et al. [6] It permits the collection of complete multidimensional NMR data sets within a single continuous acquisition. This new methodology is compatible with existing standard (TOCSY, HSQC, MRI) and recently described combined multidimensional pulse sequences, [7] and it can be implemented with conventional hardware. This attractive feature enables ultrafast NMR to examine dynamic processes, that is, organic reactions and their mechanisms as they happen in real time.[8] Figure 1 shows the schematic of the two-dimensional UF-TOCSY sequence used.[9] The sequence uses a continuous spatial encoding [10] which was implemented by pairs of RF pulses which excite/store spins over the full length, L, of the sample. The sample was swept over intervals t 1 max /2 whereas AE G e external gradients were applied. The offsets of such pulses were thus chirped over a AE gG e L/2 span, and their amplitudes calibrated as effective p/2 nutations by setting gB 1 as a function of 0.25 [(2 gG e L/t 1 max )] 1/2 .We focused our attention on one-pot syntheses of pyrimidines and similar heterocyclic compounds, which we had previously developed. [11] Pyrimidines are an important class of compounds which includes numerous natural, pharmaceutical, and functional materials.[12] Elegant new procedures have been described [13] and revealed decisive information on the mechanistic details of the reaction between carbonyl compounds and strong electrophiles such as trifluoromethanesulfonic acid anhydride (Tf 2 O). [11,14] In spite of the importance of these reactions, no spectroscopic confirmation of the postulated intermediates or kinetic data on the reaction have been reported.Using a medium field 500 MHz spectrometer, we have now applied UF NMR methodology to monitor the reaction between aliphatic ketones and Tf 2 O in the presence of nitriles. We have determined how the signals of the starting and final products evolve as they happen, in real time and attempted to detect the presence of intermediates. We chose a symmetric aliphatic ketone, 3-pentanone (1), as the model compound to react with a two-fold amount of Tf 2 O in [D 3 ]acetonitrile, which served as both a co-reactant and solvent.Scheme 1 shows the previously proposed reaction mec...
Ultrafast 2D HMBC spectroscopy permits real-time monitoring of a reaction based on the structural changes produced in a carbonyl carbon atom. This new technique was used to study the reaction of ketones, nitriles, and Tf(2)O, affording relevant information about new intermediates and kinetic data.
The reactions of the hexahydride complex OsH 6 (P i Pr 3 ) 2 (1) with 4,5-dimethyl-2,6-bis(4-methylphenyl)pyrimidine (H 2 L1), 2,4,6-tris-(4-methylphenyl)-1,3,5-triazine (H 4 L2), and 2,4,6-triphenylpyrimidine (H 4 L3) have been studied. Complex 1 reacts with H 2 L1 to give a mixture of the metallapolycyclic derivatives OsH 3 (HL1)(P i Pr 3 ) 2 (2) and OsH 2 (L1)(P i Pr 3 ) 2 (3). Compound 2 arises from the coordination of the N3-pyrimidine nitrogen atom to osmium and the ortho-CH bond activation of the C2-bonded phenyl group. The formation of 3 involves the coordination of the N1-pyrimidine nitrogen atom to osmium and the ortho-CH bond activation of both phenyl groups. The reaction of 1 with H 4 L2 leads to a mixture of OsH 2 (H 2 L2)(P i Pr 3 ) 2 (4) and (P i Pr 3 ) 2 H 2 Os-(L2)OsH 2 (P i Pr 3 ) 2 (5), containing five and eight fused rings, respectively. Complex 4 results from the coordination of the N1-triazine nitrogen atom to osmium and the ortho-CH bond activation of the phenyl groups at positions 2 and 6 of the triazine ring. Complex 5 results from the coordination of the N1 and N3 of triazine to two different metal centers along with a double ortho-CH bond activation in each proximal phenyl group. Complex 1 reacts with H 4 L3 to afford OsH 2 (H 2 L3)(P i Pr 3 ) 2 (6) and (P i Pr 3 ) 2 H 2 Os(L3)OsH 2 (P i Pr 3 ) 2 (7), which are related to 4 and 5, respectively. Complexes 2, 3, 4, and 5 have been characterized by X-ray diffraction analysis. The structures prove the planarity of their cores and suggest electron delocalization through the polycyclic system. Quantum chemical calculations (DFT level) on model compounds clearly indicate that the Os-C and Os-N bonds of the newly formed metallapolycycles exhibit a remarkable double-bond character that is higher for the Os-C bond, in very good agreement with the experimental findings.
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