The Diastereoselective Synthesis of Pyrroloindolines by Pd-Catalyzed Dearomative Cycloaddition of 1-Tosyl-2-vinylaziridine to 3-Nitroindoles

Abstract

An efficient, diastereoselective synthesis of densely functionalized pyrroloindolines is reported. The reaction proceeds via cycloaddition of a vinylaziridine-derived Pd-stabilized 1,3-dipole to electron-deficient 3-nitroindoles. The reactions give the trans diastereoisomer with high selectivity; however, when a 4-substituent is present on the indole ring, a reversal of diastereoselectivity is observed.

Diastereo‐ and Enantioselective Palladium‐Catalyzed Dearomative [3+2] Cycloaddition of 3‐Nitroindoles

“…Then, higher diastereo-and enantioselectivities were observed by lowering the reactiont emperature to À40 8Ca nd À60 8C( entries 12 and 13);afurtherd ecrease of temperature to À78 8Cr educed the yield to 80 %( entry 14). Further different Walphos ligandso ptimization confirmed that L9 was the optimal choice in terms of yield and enantioselectivity (entry 12 versus entries [15][16][17].…”

“…[2c, 14] Recently,aPd-Catalyzed [3+ +2] cycloaddition of vinyl aziridine and 3-nitroindoles was reported by Ryan and Hyland, however,o nly diastereoselective cyclization wasr ealized. [15] We have reportedt he Pd-catalyzeda symmetric [3+ +2] cycloaddition of nitroalkenes with vinyl epoxides, [16b] as part of our ongoing efforts, [8,16] the Pd-catalyzed[ 3 + +2] cycloaddition reactionu sing different reactants has been studied further. Hereinw er eported the asymmetric[ 3 + +2] cycloaddition of 3nitroindoles with vinyl aziridines.…”

Recent Developments in Transition Metal‐Catalyzed Dearomative Cyclizations of Indoles as Dipolarophiles for the Construction of Indolines

“…In 2017, Hyland and co‐workers reported the diastereoselective [3+2] cyclization reactions of 3‐nitroindoles 71 with 2‐vinyl‐ N ‐tosylaziridine 108 (Scheme ) . These reactions gave trans ‐pyrroloindolines 109 in high yields with high diastereoselectivities in most cases, and cis products could be obtained from C‐4 substituted indoles.…”

Utilizing Palladium‐Stabilized Zwitterions for the Construction of N‐Heterocycles

“…Recently, Hyland has demonstrated the first dearomative cyclization reaction employing vinylaziridines (Scheme ) . The palladium catalyzed coupling of N ‐tosyl‐2‐vinylaziridine with a variety of 3‐nitroindoles was shown to furnish the corresponding pyrroloindoline products in good to excellent yields.…”

“…Recently,H yland has demonstrated the first dearomative cyclization reaction employing vinylaziridines (Scheme 41). [58] The palladium catalyzed coupling of N-tosyl-2-vinylaziridine with av ariety of 3-nitroindoles was shown to furnish the corresponding pyrroloindoline products in good to excellent yields. Importantly,anitro substituent at the 3-position of the indole ring provedc ritical for the reaction as did the presence of a strong electron withdrawingg roup on the indole nitrogen.…”