81311-83-3Relevant academic research and scientific papers
Efficient α-Alkylation of Arylacetonitriles with Secondary Alcohols Catalyzed by a Phosphine-Free Air-Stable Iridium(III) Complex
Panda, Surajit,Saha, Ratnakar,Sethi, Subrat,Ghosh, Rahul,Bagh, Bidraha
, p. 15610 - 15621 (2020/12/01)
A well-defined and readily available air-stable dimeric iridium(III) complex catalyzed α-alkylation of arylacetonitriles using secondary alcohols with the liberation of water as the only byproduct is reported. The α-alkylations were efficiently performed at 120 °C under solvent-free conditions with very low (0.1-0.01 mol %) catalyst loading. Various secondary alcohols including cyclic and acyclic alcohols and a wide variety of arylacetonitriles bearing different functional groups were converted into the corresponding α-alkylated products in good yields. Mechanistic study revealed that the reaction proceeds via alcohol activation by metal-ligand cooperation with the formation of reactive iridium-hydride species.
Enantioselective Rhodium-Catalyzed Allylic Alkylation of Prochiral α,α-Disubstituted Aldehyde Enolates for the Construction of Acyclic Quaternary Stereogenic Centers
Wright, Timothy B.,Evans, P. Andrew
supporting information, p. 15303 - 15306 (2016/12/09)
A highly enantioselective rhodium-catalyzed allylic alkylation of prochiral α,α-disubstituted aldehyde enolates with allyl benzoate is described. This protocol provides a novel approach for the synthesis of acyclic quaternary carbon stereogenic centers and it represents the first example of the direct enantioselective alkylation of an aldehyde enolate per se. The versatility of the α-quaternary aldehyde products is demonstrated through their conversion to a variety of useful motifs applicable to target-directed synthesis. Finally, mechanistic studies indicate that high levels of asymmetric induction are achieved from a mixture of prochiral (E)- and (Z)-enolates, which provides an exciting development for this type of transformation.
Steric Inhibition of Synergistic Radical Stabilizing Effects
Bordwell, F. G.,Bausch, Mark J.,Cheng, Jin-Pei,Cripe, Thomas H.,Lynch, Tsuei-Yun,Mueller, Mark E.
, p. 58 - 63 (2007/10/02)
Equilibrium acidities in Me2SO for 14 α-N-morpholinyl-, 6 α-N-piperidinyl-, and 7 α-cyclohexylarylacetonitriles and the oxidation potentials of their conjugate bases have been determined.The increased pKHA values by about 2 units observed in these systems, relative to the corresponding arylacetonitriles, is ascribed to the presence of increased steric constraints in the anions.Hammett plots revealed larger ρ values than for arylacetonitriles (6-7 versus 5.5), pointing to an increased negative charge density on the benzylic carbon atoms in the anions.A plot of anion oxidation potentials, Eox(A-), versus pKHA for the α-N-morpholinylarylacetonitriles was linear with a slope near unity, showing that remote substituents for the most part have very little effect on radical stabilities.A 5 and 6 kcal/mol lowering of the BDE of the acidic C-H bond caused by replacing the cyclohexyl group in α-cyclohexylphenylacetonitrile by α-N-morpholinyl or N-piperidinyl groups, respectively, is attributed to the strong donor properties of these amino functions.The effects are only about one-third as large, however, as similar effects in R2NCH2COPh, where the steric effect of Ph is absent and a synergistic effect is believed to be operative.
Synthesis and Cardiovascular Activity of a New Series of Cyclohexylaralkylamine Derivatives Related to Perhexiline
Leclerc, Gerard,Decker, Nicole,Schwartz, Jean
, p. 709 - 714 (2007/10/02)
A series of 24 cyclohexylaralkylamine derivatives related to perhexilene has been synthesized and screened for cardiovascular activity.All the compounds contained an exocyclic amine which was substituted either by an alkyl, cycloalkyl, or aralkyl group.In the hope of further reducing toxicity, the synthesis of p-tolyl- and p-hydroxyphenyl derivatives 23 and 24 was undertaken.The effect of separating the cyclohexylamine moiety with respect to the aromatic nucleus has been systematically examined.The pharmacological investigations were directed to a search for compounds having an activity better than perhexiline according to the following order of criteria: (1) α-adrenolytic activity; (2) increase of coronary blood flow; (3) calcium antagonism.Several compounds were more potent and exhibited lower toxicity than perhexiline.Further detailed pharmacological investigations (tension time index and decreased cardiac work) have led to the selection of N,2-dicyclohexyl-2-phenethylamine (3) for clinical trials, which are now under way.
