Activation of the NC–H bond of Morita–Baylis–Hillman adducts of N-substituted isatins with cerium ammonium nitrate (CAN) and alcohol (ROH)

Abstract

A study on the activation of the NC-H bond of Morita-Baylis-Hillman adducts of N-substituted isatin with cerium ammonium nitrate (CAN) and saturated and unsaturated alcohols have been carried out. The choice of a Morita-Baylis-Hillman adduct for this study is screened with a number of adducts. A comparative and reactivity pattern study on NC-H activation of Morita-Baylis-Hillman adducts of N-substituted isatin derivatives viz. N-methyl, N-ethyl, N-methyl acetate, N-benzyl, N-propargyl, and N-isopropyl isatins have been carried out. Effect of aryl ring substitution has also been investigated. A plausible mechanism for the formation of the ether products has been outlined.

Synthesis of Substituted Isatins from the MBH Adduct of 1,5,6-Trisubstituted Isatins Using (2,4-Dinitrophenyl)hydrazine and K-10 Clay Explored as Protection–Deprotection Chemistry

“…Consequently, starting materials 2a – 4a for eqs 1, 2, and 3 were prepared by general N -alkylation of the isatin procedure. However, starting materials 5a – 7a for eqs 4, 5, and 6 were prepared from our own previous procedures. − …”

“…The C-3 position of isatin is protected by means of MBH adduct formation using methyl acrylate or acrylonitrile with DABCO to get the compound 2a/3a (30 min for the nitrile adduct; 3–6 days for the acrylate adduct). The MBH adduct 2a/3a is treated with CAN in a 1:1 methanol/acetonytrile solvent mixture to afford either five formyl derivatives or one ( N -methylene methylether) , position of the functionalized MBH adduct of isatin 2a ′ /3a ′. Then, the adduct 2a ′ /3a ′ is treated with 1.2 equiv of 2,4-dinitrophenylhydrazine to afford the C–C bond-cleaved phenylhydrazone product 2b/3b .…”

Synthesis of 5-aryl-3,3′-bis-indolyl and bis-7-aza-indolyl methanone derivatives from 5-bromo-7-azaindoles via sequential methylenation using microwave irradiation, CAN oxidation, and Suzuki coupling reactions

“… 6 Cerium( iv ) ammonium nitrate (CAN) has emerged as a versatile reagent for a variety of synthetic transformations which have been well documented. 7 Conversion of 3-methylenation products of indoles and 7-azaindoles to corresponding ketones are interesting synthetic modifications and no reports are available using mild and efficient reagents. Thus, we were interested to develop the oxidation of 3-methylenation products of indoles and 7-azaindoles using CAN as a one-electron oxidant into the corresponding ketones.…”

Diastereoselective Construction of Tetrahydro-Dispiro[indolinone-3,2′-pyran-5′,4″-pyrazolone] Scaffolds via an Oxa-Michael Cascade [4 + 2] Annulation Reaction

“…Despite these significant developments, the hydroxyl group of Is-MBH alcohols possesses low reactivity, is reluctant to participate in [3 + n ] annulation reactions due to its poor leaving nature, and requires strong conditions that often lead to the unwanted regio-isomers, byproducts with lower selectivity . Therefore, it remains essential to manipulate further around the Is-MBH structures.…”