1,5-O → N Carbamoyl Snieckus–Fries-Type Rearrangement

Abstract

The reaction of o-lithiated O-aryl N,N-diethylcarbamates with (hetero)aromatic nitriles gives rise to functionalized salicylidene urea derivatives in high yields through a new 1,5-O → N carbamoyl migration. This Snieckus-Fries-type rearrangement nicely complements previously known O → C and O → O related shifts. In addition, when dimethylmalononitrile is used as the electrophilic partner, the carbamoyl shift is preferred over the expected transnitrilation reaction.

Experimental and Computational Study of the 1,5-O → N Carbamoyl Snieckus–Fries-Type Rearrangement

“…Looking for a suitable method for the preparation of 6-halo-2-hydroxybenzophenone derivatives, we found that the reaction of o-lithiated O-arylcarbamates 2, readily generated by the o-lithiation of N,N-diethylcarbamates 1, with (hetero)aromatic nitriles gave rise to salicylidene urea derivatives 3 in high yields after hydrolysis with aqueous NH 4 Cl (Scheme 2). 23 Starting from O-3-fluorophenyl carbamate 1a, a wide variety of (hetero)aromatic nitriles were shown to participate in this 1,5-O → N carbamoyl translocation, although nitrile-bearing αhydrogens, such as MeCN or c-C 3 H 5 CN, underwent competitive acid−base reactions leading to the hydrolysis of 2 and the recovery of the starting carbamate. 24 Regarding the scope of the O-aryl carbamate partner 1, we demonstrated that the rearrangement is quite general as carbamates bearing no functional group, halogens, or methoxy substituents at different positions efficiently underwent the translocation.…”

“…Thus, the intermediate lithiated imine V, generated by the reaction of the corresponding o-lithiated carbamate 2 with DMMN, evolves through the 1,5-O → N carbamoyl rearrangement leading to the cyano-functionalized urea derivatives 5 in high yields (Scheme 3, eq 3). 23 Moreover, with carbamates 1 that do not possess an halogen at the meta-position, such as unfunctionalized 1b and p-substituted 1e,h,s,t, the reactions of their olithiated anions 2 with DMMN afforded new enamide derivatives 6 in moderate to good yields after purification. For their formation, we propose that the corresponding rearranged product 5 is initially generated, 27 which upon acid hydrolysis in the purification process by silica gel column chromatography leads to unstable intermediate VI that easily releases CO 2 giving rise to the isolated enamide 6 (Scheme 3, eq 4).…”

“…methylprop-1-en-1-yl)urea derivatives 6. Characterization and spectral data of compounds 4 22f and 5 23 have been previously reported.…”

“…Characterization and spectral data of 3 have been previously reported in our previous communication. 23 General Procedure for the Synthesis of Dicyano-Functionalized O-Aryl Carbamates Derivatives 4 and Urea Derivatives 5 and 6. A solution of the corresponding O-aryl N,N-diethylcarbamate 1 (1 mmol) in THF (2 mL) at −78 °C under nitrogen was treated with a solution of s-BuLi (1.4 M solution in cyclohexane, 1.1 mmol for 1a,j− n,o−r or 1.2−1.3 mmol for 1b,e,h,s,t).…”

Transition Metal-Free Synthesis of Halobenzo[b]furans from O-Aryl Carbamates via o-Lithiation Reactions

“…Although our route to access 4-halobenzo[b]furans was practical and efficient, starting from readily available halophenyl carbamates, it suffers from the use of transition metal complexes as well as the need for an iodine atom at the ortho-position, which is subsequently consumed in the Sonogashira coupling. In this context, and following our interest in the development of synthetic strategies based on the applications of directed ortho metalation reactions [19][20][21][22], we reasoned that if we were able to prepare O-2-alkynylaryl N,N-diethycarbamates in a straightforward manner from the intermediate O-2-lithioaryl carbamates, we would circumvent the prior synthesis and isolation of an iodoaryl carbamate. In addition, we also envisaged that the subsequent alkaline hydrolysis of the carbamate group in the intermediate 2-alkynylaryl carbamates would deliver a phenoxide that could undergo in situ cyclization providing the corresponding halobenzo[b]furans (Scheme 1C).…”