Premium
Stereochemistry and Mechanism of the Brønsted Acid Catalyzed Intramolecular Hydrofunctionalization of an Unactivated Cyclic Alkene
Author(s) -
McKinney Brooner Rachel E.,
Widenhoefer Ross A.
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201003128
Subject(s) - intramolecular force , chemistry , hydroamination , triflic acid , alkene , medicinal chemistry , protonation , kinetic isotope effect , sulfonamide , catalysis , stereochemistry , deuterium , organic chemistry , ion , physics , quantum mechanics
Through employment of deuterium‐labeled substrates, the triflic acid catalyzed intramolecular exo addition of the XH(D) (X=N, O) bond of a sulfonamide, alcohol, or carboxylic acid across the CC 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‐ c yclohex‐2′‐enyl‐2,2‐diphenylethyl)‐ p ‐toluenesulfonamide ( 1 a ) established the second‐order rate law: rate= k 2 [HOTf][ 1a ] and the activation parameters Δ H ≠ =(9.7±0.5) kcal mol −1 and Δ S ≠ =(−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 1 a , consistent with partial CN 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 1 a involving concerted, intermolecular proton transfer from an N‐protonated sulfonamide to the alkenyl C3′ position of 1 a coupled with intramolecular anti addition of the pendant sulfonamide nitrogen atom to the alkenyl C2′ position.