Modular Bi‐Directional One‐Pot Strategies for the Diastereoselective Synthesis of Structurally Diverse Collections of Constrained β‐Carboline‐Benzoxazepines

• Published in: Chemistry : a European journal 2017-10, Vol.23 (57), p.14182-14192
• Main Authors: Srinivasulu, Vunnam, Mazitschek, Ralph, Kariem, Noor M., Reddy, Amarnath, Rabeh, Wael M., Li, Liang, O'Connor, Matthew John, Al‐Tel, Taleb H.
• Format: Article
• Language: English
• Subjects: aza-Michael addition; benzoxazepines; diversity oriented synthesis; Pictet–Spengler reaction; stereoselective synthesis
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201702495

The development of robust and efficient strategies to access structurally diverse drug‐like compound collections remains an important challenge for small molecule probe development and drug discovery. Following a build/couple/pair strategy we have established bidirectional approach to unprecedented benzoxazepines by employing a Pictet–Spengler/aza‐Michael addition cascade and Schiff base/aza‐Michael addition/reduction protocols, respectively. The corresponding β‐carboline‐fused benzoxazepines and peripherally substituted benzoxazepines are isolated in high diastereoselectivity, good to excellent yields and have, to the best of our knowledge, never been reported. Cascading rings: A bidirectional approach to unprecedented benzoxazepines has been established by employing a Pictet–Spengler/aza‐Michael addition cascade and Schiff base/aza‐Michael addition/reduction protocols, respectively. The corresponding β‐carboline‐fused benzoxazepines and peripherally substituted benzoxazepines are isolated in high diastereoselectivity, good to excellent yields and have, to the best of our knowledge, never been reported.