Kinetic secondary deuterium isotope effects for substituted benzaldehyde cyanohydrin formation

Mechanism of Amido-Thiourea Catalyzed Enantioselective Imine Hydrocyanation: Transition State Stabilization via Multiple Non-Covalent Interactions

“…In the asymmetric imine hydrocyanation, an inverse KIE of k H / k D = 0.88 ± 0.03 is observed (eq 5). An isotope effect of this magnitude allows us to rule out a late transition state involving a largely sp 3 -hybridized electrophilic carbon, but it is consistent with a transition state that involves either early C−C bond formation or iminium ion rearrangement . Therefore, the experimental secondary isotope effect data are consistent with either F or H (Scheme ) as the rate- and enantioselectivity-determining transition structures.…”

“…A key difference between these transition structures is that H undergoes partial sp 2 → sp 3 rehybridization of the electrophilic carbon atom, whereas F does not. Secondary α-hydrogen/deuterium kinetic isotope effects (KIEs, k H / k D ) are sensitive probes of changes in carbon hybridization state, and inverse α-KIEs are observed in reactions thought to involve significant sp 2 → sp 3 rehybridization (typically, k H / k D ≈ 0.75−0.90) …”

Characterization of the Lysyl Adducts Formed from Prostaglandin H2 via the Levuglandin Pathway

“…As expected, the largest products of this rearrangement were PGE 2 /D 2 (81%), but substantial amounts of LGE 2 / D 2 also were formed (18%), predominating over prostaglandin F 2R (0.4%). [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] are also present at significant levels (Figure 2).…”

“…All three of these species correspond to molecular ions of predicted cyano-lysyl-LG Schiff bases. Cyanide can add to the electrophilic imine () or carbonyl ( − ) carbon and by Michael addition to the β-carbon of carbonyl-conjugated carbon−carbon double bonds (). As the lysyl-LG and lysyl-anhydroLG Schiff base adducts have all of these functional groups, it is difficult to be definitive about the structures of the cyanide reaction products.…”