ChemInform Abstract: Phase Transfer Catalyzed Enantioselective Cyclopropanation of 4‐Nitro‐5‐styrylisoxazoles.

Abstract

Phase Transfer Catalyzed Enantioselective Cyclopropanation of 4-Nitro-5-styrylisoxazoles. -The cyclopropanation of styryl isoxazoles (I) as cinnamate equivalents with bromomalonate (II) in the presence of a Cinchona alkaloid derived phase-transfer catalyst affords highly substituted cyclopropanes (III) in high yields, complete diastereo-and high enantioselectivity. The masked carboxylate group is readily released by oxidative isoxazole cleavage [cf. (V)]. -(DEL FIANDRA, C.; PIRAS, L.; FINI, F.; DISETTI, P.; MOCCIA, M.; ADAMO*, M. F. A.; Chem. Commun. (Cambridge) 48 (2012) 32, 3863-3865, http://dx.doi.org/10.1039/c2cc30401e ; Dep. Pharm. Med. Chem., R. Coll. Surg. Ire., Dublin 2, Ire.; Eng.) -M. Paetzel 32-050

Cyclopropanation of 5-(1-Bromo-2-phenyl-vinyl)-3-methyl-4-nitro-isoxazoles under Phase Transfer Catalysis (PTC) Conditions

“…The reason for this may lay in the peculiar mode of action of these catalytic species (see Figure 2) in which a free OH is required to provide a key H-bond with the enolate. [43] Based on the results collected on N-benzylquininium catalyst series, a series of Nbenzylquininium salts was prepared containing various functional groups at the benzyl ortho-position and employed as catalysts to promote the Michael addition. These catalysts provided cyclopropane 7a in similar enantiopurity as commercially available N-benzylquininium chloride (Table 1, entries 6-9).…”

“…[40] These methodologies gave densely substituted cyclopropanes in good yields and good to excellent diastereo-and enantio-selectivity. Cyclopropanation has been scarcely studied under phase transfer catalysis [41] with Shiori's [42] and our group [43] providing the only two known examples of high enantioselective procedures. Cyclopropanation reactions which involves a conjugate addition to an electrophilic alkene to produce an enolate, which then subsequently undergoes an intramolecular ring closure, are defined as Michael-initiated ring closure (MIRC) reactions.…”

“…For example, our group has recently reported a highly enantioselective cyclopropanation of 3-methyl-4-nitro-5-styrylisoxazoles 1 that reacted with bromomalonate 6 under the catalysis of Cinchona based phase transfer catalysts [43]. The second type of MIRC processes involves the formation of cyclopropanes by nucleophilic addition to electrophilic substrates containing a leaving group, for example a bromide as in compound 2.…”