Metal-free nitro-carbocyclization of activated alkenes: a direct approach to synthesize oxindoles by cascade C–N and C–C bond formation

Abstract

A novel and direct metal-free nitro-carbocyclization of activated alkenes leading to valuable nitro-containing oxindoles via cascade C-N and C-C bond formation has been developed. The mechanistic study indicates that the initial NO and NO2 radical addition and the following C-H functionalization processes are involved in this transformation.

Cascade Nitration/Cyclization of 1,7‐Enynes with tBuONO and H2O: One‐Pot Self‐Assembly of Pyrrolo[4,3,2‐de]quinolinones

“…[9] Proposed reaction mechanisms based on the above results [9] and previous reports [6-8, 11, 12] are shown in Scheme 2. Initially, addition of NO 2 , which is generated in situ from tBuONO, [8,11,12] to the carbon-carbon double bond of the 1,7enyne 1 a gives alkyl radical intermediate A, which cyclizes to form intermediate B. The reaction of intermediate B with NO or NO 2 affords the corresponding intermediates C and C', which was supported by HRMS analysis.…”

“…It has been reported that 2,2,6,6-tetramethylpiperidin-1-yl)oxy (TEMPO), a radical initiator, proved beneficial in some nitration reactions using tBuONO. [8] However, the presence of TEMPO suppressed the current reaction (entries 4 and 5): the yield of product 2 a decreased from 78 % to 67 % with 20 mol % TEMPO and to 53 % with 100 mol % TEMPO. Notably, a good yield was even achieved under N 2 atmosphere when DMSO was purged with N 2 (entry 6).…”

“…[6] Among these processes, the cyclization of 1,n-enynes is a particularly effective and atom-economical step for constructing the ring systems. [6,7] Herein, we report an unprecedented cascade nitration/cyclization of N-(2-(ethynyl)aryl)acrylamides (1) with tBuONO and H 2 O for the onepot synthesis of pyrrolo [4,3,2-de]quinolinone architectures under metal-free conditions (Scheme 1); [8] this is realized through a cascade of alkene nitration, 1,7-enyne 6-exo-trig cyclization, CÀH nitrations, and redox cyclization, representing the first example of a one-pot assembly of the pyrrolo- [4,3,2-de]quinolinone scaffold.…”

tert-Butyl Nitrite

“…17 The transformation has a large substrate scope and allows the formation of biologically valuable compounds. 8-Methylquinolines are selectively nitrated through sp 3 C-H activation in the presence of catalytic amounts of palladium acetate in moderate to good yields (eq 13).…”

Metal-free direct cyanoisopropylation/arylation of N-arylacrylamides or N-alkyl-N-(arylsulfonyl)acrylamides with AIBN: a simple and mild approach to cyano-containing oxindoles

“…As a part of our continuing interest in the metal-free C-H functionalization/cyclization reactions. 15, 16 Herein we present an operationally simple and highly efficient cyanoisopropylation/ arylation without using any metal catalysts and additional oxidants, thus becoming a powerful alternative for accessing cyanocontaining oxindoles in a direct manner. Compared with previous reports, the significance of the present finding is twofold: (1) This transformation exhibits good generality: the substrate scope is not only applicable to N-arylacrylamides, but also to N-alkyl-N-(arylsulfonyl)acrylamides.…”