Establishing the concept of aza-[3 + 3] annulations using enones as a key expansion of this unified strategy in alkaloid synthesis

• Aleksey I. Gerasyuto,
• Zhi-Xiong Ma,
• Grant S. Buchanan and
• Richard P. Hsung

Beilstein J. Org. Chem. 2013, 9, 1170–1178, doi:10.3762/bjoc.9.131

• synthesis; catalysis; enones; intramolecular aza-[3 + 3] annulation; N-heterocycles; natural product; vinylogous amides; Introduction Throughout the past decade, we have been developing an aza-[3 + 3] annulation reaction as a general and unified strategy in alkaloid synthesis [1][2][3][4][5][6][7][8][9][10

• ][13][14][15]. The intramolecular variant of this annulation has proven to be particularly valuable for total synthesis [16][26][27][28][29][30][31][32]. Specifically, the intramolecular aza-[3 + 3] annulation of vinylogous amides tethered to a vinyl iminium motif 1a proceeds through a tandem sequence

• To examine the feasibility of an enone intramolecular aza-[3 + 3] annulation, a seven-step synthesis of the annulation substrate 10 commencing from 3-butyn-2-ol (5) was carried out (Scheme 2). Protection of secondary propargyl alcohol 5 as the THP-ether followed by alkylation of a lithium acetylide