Origin and remedy for HSQC artifacts in proton-detected INADEQUATE spectra

Abstract

NMR pulse sequences visualizing ¹J_CC and ⁿJ_CC bond connectivity via an intermediate state of ¹³C–¹³C double-quantum coherence and ¹H detection are an indispensable tool to solve small-molecule structures at the natural abundance level of ¹³C. A longstanding issue with these experiments set up to display 2D spectra with single-quantum frequencies is that in addition to the ¹H–¹³C–¹³C correlations of interest, appearance of HSQC-type artifacts can complicate analysis and obscure J_CC connectivities. The origin of these artifacts is described and remedies for their suppression are introduced. They include refocusing of ¹J_CH couplings prior to creation of ¹³C–¹³C double-quantum coherence, which is known to enhance sensitivity by reducing loss into zero-quantum coherence for pairs of two protonated ¹³C.