Stereoselective Synthesis of Isoquinuclidines through an Aza-[4 + 2] Cycloaddition of Chiral Cyclic 2‑Amidodienes

A highly stereoselective aza-[4 + 2] cycloaddition of chiral cyclic 2-amidodienes with <i>N-</i>sulfonyl aldimines is described. While this Lewis acid promoted heterocycloaddition provides an efficient strategy for constructing optically enriched isoquinuclidines, it is mechanistically intriguing. The cycloaddition favored the <i>endo-II</i> pathway in the absence of a viable bidentate coordination. This represents an unexpected switch from the anticipated <i>endo-I</i> selectivity obtained in the all-carbon cycloaddition

Total Syntheses of (±)-Rhodonoids A and B and C12-<i>epi</i>-Rhodonoid B

Total syntheses of (±)-rhodonoids A and B and C12-<i>epi</i>-rhodonoid B are described here. A unified strategy employed in these syntheses is an intramolecular <i>oxa</i>-[3 + 3] annulation for accessing the chromene unit. A Fe­(OTf)₃-promoted diastereoselective cationic [2 + 2] cycloaddition and a photochemical [2 + 2] cycloaddition were featured to construct the cyclobutane core of (±)-rhodonoids A and B and C12-<i>epi</i>-rhodonoid B, respectively. Fe­(OTf)₃ also leads to an interesting bridged tetracycle, which was unambiguously confirmed by single crystal X-ray analysis

Total Syntheses of (±)-Rhodonoids C, D, E, F, and G and Ranhuadujuanine B

Here we describe the divergent, biosynthetically inspired syntheses of (±)-rhodonoids C–G and (±)-ranhuadujuanine B. The key steps of the syntheses include the construction of the chromene unit through a formal oxa-[3 + 3] annulation and a biomimetic acid-catalyzed ring cyclization. Cationic [2 + 2] cycloaddition is accomplished to form the cyclobutane core of (±)-rhodonoids E and F

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

A successful enone version of an intramolecular aza-[3 + 3] annulation reaction is described here. Use of piperidinium trifluoroacetate salt as the catalyst and toluene as the solvent appears to be critical for a successful annulation. We also demonstrated for the first time that microwave irradiation can accelerate aza-[3 + 3] annulation reactions. An attempt to expand the scope of the enone aza-[3 + 3] annulation was made in the form of propyleine synthesis as a proof of concept. While synthesis of the enone annulation precursor was successfully accomplished, the annulation proved to be challenging and was only modestly successful

Gassman’s Cationic [2 + 2] Cycloadditions Using Temporary Tethers

An intermolecular equivalent of Gassman’s cationic [2 + 2] cycloaddition through the use of temporary tethering is described. Notably, hydrazine and hydroxyamide proved to be robust under the acidic conditions required for the cycloaddition, leading to unique cyclobutane manifolds in a highly regio- and stereoselective manner. This development represents a rare usage of hydrazine and hydroxyamide in the capacity as temporary tethers