Rhodium-Catalyzed Ring Expansion of Azetidines via Domino Conjugate Addition/N-Directed α-C(sp³)–H Activation

Abstract

A facile synthetic method for 4-aryl-4,5-dihydro­pyrrole-3-carboxylates is developed, with a rhodium-catalyzed ring expansion strategy from readily available 2-(azetidin-3-ylidene) acetates and aryl boronic acids. Mechanistic investigations suggest a novel domino “conjugate addition/N-directed α-C­(sp3)–H activation” process. The asymmetric catalytic synthesis of the 4-aryl-4,5-dihydro­pyrrole-3-carboxylate is realized by using QuinoxP* (91–97% ee). The synthetic utility of this protocol is demonstrated by the synthesis of 3,4-disubstituted or 2,3,4-trisubstituted pyrrolidines with excellent diastereoselectivities.

P-Stereogenic Phosphorus Ligands in Asymmetric Catalysis

“…Recently, Xie and co-workers have reported an interesting ring expansion reaction of azetidines 135 promoted by the Rh−QuinoxP* catalyst (Scheme 145). 562 This transformation took place requiring a ketone oxidant (9-fluorenone) and accompanied an asymmetric arylation to give 4,5-dihydropyrroles 136 in moderate yields and high enantioselectivities. The products were readily derivatized into 3,4-disubstituted or 2,3,4-trisubstituted pyrrolidines without loss of the enantiopurity.…”

Rhodium-Catalyzed Ring Expansion and Ring Opening of ­Azetidines: Domino Conjugate Addition/Inert-Bond Activation

“…10,11 In fact, a ring-expansion product containing a 4-phenyl-4,5-dihydropyrrole-3-carboxylate unit was isolated and identified from the mixed products, along with a similar enamine product, a conjugate-addition product, and a reduction product (Scheme 8). 12 Because 2-pyrroline and 3,4disubstituted pyrrolidine are core structures of many pharmacologically active molecules, 13 this would be a useful synthetic method, considering the convenient availability of 2-(azetidin-3-ylidene)acetates and arylboronic acids.…”

Cu-catalyzed decarboxylative annulation of proline derivatives: multi-component synthesis of functionalized chromeno[2,3-c]-pyrrol-9(1H)-one derivatives

“…Due to the unique biological activities of pyrrolidines, a significant number of synthetic strategies have been developed over the years to construct pyrrolidine rings, including meta-catalyzed intramolecualr cyclization, 18 [3 + 2] cycloaddition, 19 bis-Michael reaction, 20 ring expansion, 21 and three-component reaction of α-diazo ester. 22 Although these methods are crucial for the synthesis of these compounds, their disadvantages include inaccessible starting materials and the pre-functionalized substrates are obtained via tedious multiple steps, with limited substrate scope and simple structures of the target compounds. Hence, it is highly desirable to develop novel multi-component cascade reactions for the synthesis of functionalized pyrrolidines that enable the formation of multiple bonds in fewer steps.…”