Stereochemistry and mechanism of the Brønsted acid catalyzed intramolecular hydrofunctionalization of an unactivated cyclic alkene.

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.

Duke Scholars

Author Ross A. Widenhoefer Chemistry