Organic Chemistry

Cis-selective double spirocyclization via dearomatization and isomerization under thermodynamic control



Spiro compounds have been considered key scaffolds for pharmaceutical applications. Although many synthetic methods exist for monospirocycles, fewer approaches are known for dispirocycles. Here, we report a highly cis-selective method for constructing a 5/6/5-dispirocyclic structure containing pyrrolidine and γ-lactam rings with various substit-uents from a series of N-arylpropiolamides. The high cis-selectivity would result from isomerization under thermody-namic control. Cis- and trans-diastereomers can be in equilibrium, favoring cis-adducts.

Version notes

Additional experiments were included: Entries 6 and 9 in Table 1 Entries 12 and 13 in Table 2 Two reactions in Scheme 4


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Supplementary material

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Supporting Information
Result of control experiments Result of calculation of the relative energies NMR spectra of synthetic compounds