title: Stereochemistry and mechanism of the Brønsted acid catalyzed intramolecular hydrofunctionalization of an unactivated cyclic alkene.
abstract: Through employment of deuterium-labeled substrates, the triflic acid catalyzed intramolecular exo addition of the X-H(D) (X=N, O) bond of a sulfonamide, alcohol, or carboxylic acid across the C=C bond of a pendant cyclohexene moiety was found to occur, in each case, with exclusive formation (≥90%) of the anti-addition product without loss or scrambling of deuterium as determined by (1)H and (2)H NMR spectroscopy and mass spectrometry analysis. Kinetic analysis of the triflic-acid-catalyzed intramolecular hydroamination of N-(2-cyclohex-2'-enyl-2,2-diphenylethyl)-p-toluenesulfonamide (1a) established the second-order rate law: rate=k(2)[HOTf][1a] and the activation parameters ΔH(++)=(9.7±0.5) kcal mol(-1) and ΔS(++)=(-35±5) cal K(-1) mol(-1). An inverse α-secondary kinetic isotope effect of k(D)/k(H) =(1.15±0.03) was observed upon deuteration of the C2' position of 1a, consistent with partial C-N bond formation in the highest energy transition state of catalytic hydroamination. The results of these studies were consistent with a mechanism for the intramolecular hydroamination of 1a involving concerted, intermolecular proton transfer from an N-protonated sulfonamide to the alkenyl C3' position of 1a coupled with intramolecular anti addition of the pendant sulfonamide nitrogen atom to the alkenyl C2' position.
authors.affiliation: Department of Chemistry, Duke University, French Family Science Center, Durham, NC 27708, USA.
authors.forename: Rachel E McKinney
authors.initials: RE
authors.lastname: Brooner
authors.forename: Ross A
authors.initials: RA
authors.lastname: Widenhoefer
mesh_terms: D002384:Catalysis; D003516:Cycloparaffins / Q000737:chemistry*; D003903:Deuterium / Q000737:chemistry*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013237:Stereoisomerism; D013449:Sulfonamides / Q000737:chemistry*; D014050:Toluene / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D003516:Cycloparaffins; C559769:N-(2-cyclohex-2'-enyl-2,2-diphenylethyl)-p-toluenesulfonamide; D013449:Sulfonamides; D014050:Toluene; D003903:Deuterium