Measurement of deuterium kinetic isotope effects in organic reactions by natural-abundance deuterium NMR spectroscopy

Pd/Cu‐Catalyzed Cross‐Coupling of Densely Substituted Propargylamines with Aromatic Acyl Chlorides Followed by the Treatment with a Base: Access to Dihydro‐3H‐Pyrrol‐3‐Ones

“…Propargylamines 1 were prepared from aryl(hetaryl)ketimines and acetylene as previously described. [10] The 1 H and 13 C NMR spectra were recorded on a Bruker DPX 400 and Bruker AV-400 spectrometer (400.13 and 100.62 MHz, respectively) in CDCl 3 solutions and referenced to HMDS ( 1 H, 13 C). The assignment of signals in 1 H spectra was performed using 2D homonuclear correlation method COSY.…”

“…1 H NMR (400.13 MHz, CDCl 3 ): δ 7.99 (d, 1H, 3 J = 8.1 Hz, H5''), 7.83 (d, 1H, 3 J = 7.9 Hz, H8''), 7.74 (m, 2H, Ho), 7.55 (d, 1H, 3 J 5'-4' = 1.5 Hz, H5'), 7.52 (m, 1H, H6''), 7.49 (m, 1H, H7''), 7.38 (m, 2H, Hm), 7.32 (m, 1H, Hp), 7.29 (d, 1H, 3 J = 7.8 Hz, H2''), 7.14 (t, 1H, 3 J = 7.9 Hz, H3''), 6.87 (d, 1H, 3 J 3'-4' = 3.6 Hz, H3'), 6.52 (d, 1H, 3 J = 7.8 Hz, H4''), 6.38 (dd, 1H, 3 J 4'-3' = 3.6 Hz, 3 J 4'-5' = 1.5 Hz, H4'), 5.03 (br.s, 1H, NH), 2.08 (s, 3H, 4-Me) ppm. 13 C{ 1 H} NMR (100.62 MHz, CDCl 3 ): δ 164.4 (C=O), 153.1 (C2'), 148.2 (C5'), 142.4 (Ci), 139.2 (C4a), 134.3 (C8a), 129.0 (Cm), 128.9 (Cp), 127.9 (C8''), 125.9, 125.8 (C6'',7''), 125.4 (C3''), 125.3 (Co), 124.3 (C1''), 121.9 (C3'), 119.8 (C5''), 119.1 (C2''), 112.7 (C4'), 110.5 (C4''), 95.1 (C3), 81.6 (C2), 56.1 (C4), 35.5 (4-Me) ppm. HRMS (ESI-TOF) calcd for [C 25 H 19 NO 2 + H] + 366.14940, found 366.14976.…”

“…Following the general procedure, 2 u was prepared from N-(1ethynylcyclohexyl)aniline (0.399 g, 2.0 mmol) and 2-thenoyl chloride (0.293 g, 2.0 mmol) and isolated as a waxy product (0.507 g, 82% yield). The product is a mixture of two isomers in a ratio of 1.44:1 ( 1 H and 13 C NMR data). The existence of 2 u as two isomers is likely due to the hindered inversion of the cyclohexyl moiety that forces the substituents to occupy either equatorial or axial position.…”

“…J 5'-4' = 1.7 Hz, H5'), 7.39 (m, 2H, Hm1), 7.31 (m, 1H, Hp1), 7.10 (m, 2H, Hm2),6.77 (m, 1H, Hp2),6.73 (d, 1H, 3 J 3'-4' = 3.6 Hz, H3'),6.58 (m, 2H, Ho2), 6.39 (dd, 1H, -3' = 3.6 Hz, 3 J 4'-5' = 1.7 Hz, H4'), 4.35 (br.s, 1H, NH), 1.91 (s, 3H, 4-Me) ppm 13. C{ 1 H} NMR (100.62 MHz, CDCl 3 ): δ 164.5 (C=O), 153.2 (C2'), 148.1 (C5'), 145.0 (Ci2), 143.0 (Ci1), 129.0 (Cm2), 128.9 (Cm1), 127.9 (Cp1), 125.5 (Co1), 122.0 (C3'), 119.2 (Cp2), 116.2 (Co2), 112.7 (C4'), 95.2 (C3), 81.4 (C2), 56.5 (C4), 35.2 (4-Me) ppm.…”

Site-specific isotope effects and origin inference

“…Initially proposed for solving an important problem both in France and in Europe, the detection of illegal enrichment of wines (chaptalization) [10], the SNIF-NMR method now provides new or improved information in a wide range of fundamental or applied areas: -A simultaneous determination of primary and secondary kinetic isotope effects involving the whole set of observable isotopomers of a given molecular species is possible, without the need for selective enrichment [11][12][13][14][15][16]. The evolution of the isotope ratio at a given position i of reactant A, (D / H) A i , as a function of the fraction of reaction, ρ, and of the primary, k H / k D , or secondary, k H / k D H , kinetic isotope effects, is illustrated in figure 1 for a non-branched reaction.…”