Wright BA,
Regni A,
Chaisan N,
Sarpong R.
*
University of California, Berkeley, USA
Navigating Excess Complexity: Total Synthesis of Daphenylline.
J. Am. Chem. Soc. 2024;
146: 1813-1818
DOI:
10.1021/jacs.3c12953
Key words
(±)-daphenylline -
Daphniphyllum alkaloid - Buchner ring expansion - thia-Paternò–Büchi cycloaddition - Barton–McCombie deoxygenation
Significance
Sarpong and co-workers report the total synthesis of (±)-daphenylline. The alkaloid features a 2-azabicyclo[3.3.1]nonane core attached to a 5-7-5 ring system. Their key synthetic strategy is the formation of the seven-membered ring by a Buchner ring expansion.
Comment
Diazoacetamide F was accessed from pyridine A in three steps. After cyclopropanation, lactam I was furnished through a 6π-electrocyclic ring opening and reduction. The benzylic methyl group in amine M was installed through a thia-Paternò–Büchi cycloaddition and subsequent reduction of the thietane using LAH and Raney-Ni.
