³¹P NMR Spectroscopically Quantified Hydrogen‐Bonding Strength of Thioureas and Their Catalytic Activity in Diels–Alder Reactions

Abstract

The hydrogen‐bonding strength of a variety of commonly employed thiourea catalysts was quantified by using a trialkylphosphine oxide as a 31P NMR probe. Simple diarylthioureas and more complex bifunctional amine‐ and hydroxy‐substituted thiourea derivatives were examined. Their catalytic activity was determined in a Diels–Alder reaction, and the obtained pseudo‐first‐order rate constants were correlated with the 31P NMR chemical shifts. A linear correlation between both variables was observed throughout the functionalized thioureas. The 31P NMR probe correlation fared better in comparison to a pKa correlation. Accordingly, the quantification presented herein by using a 31P NMR probe offers an elegant way to estimate the catalytic activity of thiourea catalysts in hydrogen‐bond‐activated reactions such as the Diels–Alder reaction.

Experimental and Theoretical Studies in Hydrogen-Bonding Organocatalysis

“…Phosphine oxide 20a , which resembles a carbonyl group, was explored as 31 P-NMR signal detection-based probe (Figure 5) [29]. Upon formation of the hydrogen bond between a thiourea and the oxygen atom of 20a , the electron density is shifted towards the thiourea, resulting in the downfield shift of the 31 P-NMR signal.…”

Catalytic, Enantioselective Synthesis of Cyclic Carbamates from Dialkyl Amines by CO2-Capture: Discovery, Development, and Mechanism

“…Notably, this line of thought is counter to the prevailing wisdom encountered with many Brønsted acid catalyzed reactions. 22 , 23 , 24 In the event, the analogous catalyst 7b bearing a methyl group at the quinoline 7-position led to higher yield (31%) and enantioselection (81% ee) (Table 1, entry 5) that improved further with the C7-methoxy catalyst 7c (75% yield, 89% ee) (Table 1, entry 6). 25 Interestingly, higher substrate concentrations led to diminished yield and selectivity (Table 1, entries 7–8), concomitant with signs that the reaction mixtures were more heterogeneous due to insolubility of one or more reagents.…”

Urea‐ and Thiourea‐Catalyzed Aminolysis of Carbonates

“…For the thiourea derivatives investigated, the affinity constants were moderate but varied with the highest K value for the most acidic 5 a ( K =121 m −1 ) and the lowest K value ( K =0.67 m −1 ) for the least acidic 2 a . Hence, 1 H NMR titrations provide a useful tool to confirm the p K a determination obtained by titration, so as to predict catalytic activity …”