Synthetic studies toward longeracemine: The intramolecular [4+2] cycloaddition of 3H-pyrroles

Modular approach to non-aromatic and aromatic pyrroles through gold-catalyzed [3 + 2] cycloaddition of 2H-azirines and ynamides

“…Moreover, the high synthetic potential of 3H-pyrroles, which have found application as hetero-dienes in the Diels-Alder reaction, has been convincingly proven. [21][22][23] In recent years, significant efforts have been made to construct 3H- [24][25][26][27][28] and 2H- 24,25,[29][30][31][32][33][34][35] pyrroles. Some of the reported synthetic schemes are based on the dearomatizations of 1Hpyrroles; typically, these reactions proceed under harsh conditions.…”

“…Moreover, the high synthetic potential of 3 H -pyrroles, which have found application as hetero-dienes in the Diels–Alder reaction, has been convincingly proven. 21–23…”

Synthetic studies toward longeracemine: a SmI2-mediated spirocyclization and rearrangement cascade to construct the 2-azabicyclo[2.2.1]heptane framework

“…Recently, we reported an efficient assembly of the 2-azabicyclo[2.2.1]heptane core of 1 through an intramolecular [4+2] cycloaddition of 3H-pyrroles (Scheme 1). 4 Exposure of diols 2ab to Swern oxidation, amine condensation, and an acidmediated [4+2] cycloaddition afforded the desired bicycles 4a and 4b in 33% and 42% yields, respectively, in single pot transformations; 2c failed to afford 4c (Scheme 1a). Employing optimized conditions, the reaction of a more functionalized diol (5), to access 7, which is better poised for elaboration to longeracemine (1) compared to 4a-c was explored (Scheme 1b).…”

“…However, the [4+2] cycloaddition was found to be highly substrate dependent and the reaction of 5 failed to provide desired compound 7. 4 Based on these results, an alternative approach was required to construct the 2-azabicyclo[2.2.1] heptane framework. Herein, we report that a novel SmI 2 -mediated cascade reaction, involving a spirocyclization and rearrangement, affords a 2-azabicyclo[2.2.1]heptene framework that is suitably functionalized for advancement to 1 (Scheme 1c).…”