Observation of untoward ³J_cc correlations in 1,1‐ADEQUATE spectra of pyrimidine analogs: Avoiding potential interpretation pitfalls

Abstract

Recently, it has been reported that large J correlations can sometimes be observed in 1,1-ADEQUATE spectra with significant intensity, which opens the possibility of structural misassignment. In this work, we have focused on pyrimidine-based compounds, which exhibit multiple bond correlations in the 1,1-ADEQUATE experiment as a consequence of J coupling constants greater than 10 Hz. Results are supported by both the experimental measurement of J coupling constants in question using J-modulated-ADEQUATE and density functional theory calculations.

19F‐detected dual‐optimized inverted 1JCC 1,n‐ADEQUATE

“…For those less familiar with how ADEQUATE correlations correspond to the much more familiar HMBC experiment, 1 J CC ADEQUATE correlations correspond to a 2 J CH HMBC correlation, and 2 J CC and 3 J CC ADE-QUATE correlations correspond to 3 J CH and 4 J CH HMBC correlations, respectively. [5][6][7] Further, while the correlation pathway in an HMBC experiment is indeterminant, in general, but not exclusively, only 1 J CC correlations are observed in a 1,1-ADEQUATE spectrum although, as we have shown previously, [19][20][21][22][23] 2 J CC and longer-range correlations can be observed in 1,1-ADEQUATE spectra, particularly when the correlation path bridges a carbonyl or when annular heteroatoms are involved. This possibility is accentuated when homodecoupled variants [25][26][27] of the ADEQUATE experiment are employed.…”

“…At a minimum, utilization of isotope shifts would prevent misinterpretation of n J CC correlations that may sometimes "leak" into 1,1-ADEQUATE spectra in cases of unusually large corresponding n J CC coupling constants. [19][20][21][22][23] While isotope shifts are not readily discernable from the full-scale plot (see Figure 5), they are quite pronounced when narrower F2 frequency domain regions of the spectrum are examined (see Figure 6), particularly when flanked by the high-resolution 19 4 Δ 19 F( 13/12 C) 1-2 Δ( 13/12-13/12 C) 1-3 Δ( 13/12-13/12 C) 1-4 Δ( 13/12-13/12 C) In contrast, all of the n J CC correlations plotted in black have positive phase. There is also a weak F2-C2 HSQC correlation that has positive phase.…”

Development of 19F‐detected 1,1‐ADEQUATE for the characterization of polyfluorinated and perfluorinated compounds

“…C5) were both weak (see also Figure 10). Although there was a possibility of observing, for example, a 2 J C6C2 correlation analogous to those observed across intervening carbonyls and other substituents in 1 H-detected 1,1-ADEQUATE experiments, [38][39][40][41] none were observed. The possibility of observing these correlations cannot, however, be ruled out…”

“…Based on the previous observation of 2 J CC correlations by several of the authors in 1 H-detected 1,1-and 1,1-HD-ADEQUATE spectra, [38][39][40][41] we also considered the possibility of, for example, a 2 J CC correlation between C6 and C2 that might be detected via the F-6 19 F resonance or conversely, a 2 J CC correlation to C6 detected via the F-2 resonance. Calculated values for these potential correlations are found in Table 1.…”

J‐modulated 19F‐ and 1H‐detected dual‐optimized inverted 1JCC 1,n‐ADEQUATE: A universal ADEQUATE experiment

“…There also exists the possibility that isotope shifts, when measured, can be used as a means of identifying the occasional 2 J CC or 3 J CC correlation observed in a 1,1-ADEQUATE experiment. [30][31][32] 4…”