![]() ![]() It should be pointed out that fused oxazepines are a very important class of biologically active molecules that display diverse pharmacological activities. 12 Herein, we report the development of a synthetic approach that allows for modular assembly of chiral medium-sized heterocycles 6 and 12 bearing a fused cyclopropane moiety. The limited availability of chiral precursors 10 warranted further studies to adapt this methodology to more stable, isolable cyclopropenes accessible via the metal-catalyzed cyclopropenation reactions. To date, only two examples were communicated by our group, 11 using cyclopropene 11 generated in situ via 1,2-elimination of bromocyclopropane 10 ( Scheme 2). A diastereoselective 8- endo-trig cycloaddition using chiral cyclopropene precursor 8 has been demonstrated ( Scheme 1, eq 3), 10 while a complementary approach involving intramolecular nucleophilic addition of tethered chiral alkoxides to prochiral cyclopropene moieties has not been fully explored. 9, 10 In all these studies achiral tethered nucleophilic entities were used for cyclizations affording racemic products. 6, 7 Both intermolecular ( Scheme 1, eq 1) and intramolecular ( Scheme 1, eq 2) addition of tethered nucleophiles, employing carbon- 8 or oxygen-based species, has been reported. Advances in base-assisted additions of heteroatom-based nucleophiles to cyclopropenes made available novel stereo-defined cyclopropyl scaffolds, 1 possessing oxygen, 2 nitrogen, 3 sulfur, 4 or halogen 5 entities, that complement transition-metal-catalyzed cyclopropanation methodologies.
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