Directed ortho‐Metalation of O‐Aryl N,N‐Dialkylcarbamates: Methodology, Anionic ortho‐Fries Rearrangement, and Lateral Metalation

Abstract

The directed ortho‐lithiation reactions of O‐aryl N,N‐dialkylcarbamates as well as O‐1‐naphthyl and O‐2‐naphthyl N,N‐dialkylcarbamates with sec‐butyllithium/tetramethylethylenediamine (sBuLi/TMEDA) followed by quenching with various electrophiles afford a range of polysubstituted aromatic compounds. If the solutions of the ortho‐lithiated carbamates are warmed to room temperature without the addition of external electrophiles, salicylamide and 1‐ and 2‐hydroxynaphthamide derivatives are formed through anionic ortho‐Fries rearrangements. The relative stabilities and reactivities of different O‐aryl N,N‐dialkylcarbamates were investigated. The lateral metalation of 2‐tolyl carbamates with lithium diisopropylamide (LDA) provides a route to benzo[b]furan‐2(3H)‐ones. Previously reported results are used in a comparison of seven O‐based directed metalation groups in reactions with several electrophiles. The described methodology is useful for the preparation of 1,2,3‐substituted aromatic compounds.

Directed ortho‐Metalation of Aryl Amides, O‐Carbamates, and Methoxymethoxy Systems: Directed Metalation Group Competition and Cooperation

“…In summary, the work presented here and in the accompanying report [37] demonstrates the superiority of the O-carbamate function as an ortho director over the chloro, methoxy, tertiary amide, and methoxymethoxy groups in DoM chemistry and leads to the conclusion that it is the functionality of paramount choice among the oxygen-based DMGs. Routes for the synthesis of a variety of substituted aryl O-carbamates through DoM and AoF rearrangement reactions have been demonstrated.…”

“…[37] ) [h] The oy is not available; the last step (deprotection) proceeds in 94 % yield. [37] ) [h] The oy is not available; the last step (deprotection) proceeds in 94 % yield.…”

“…The presence of an unreactive or protected group G such as that in 14 provides the opportunity to introduce a second DMG 2 (step a) through the use of an appropriate electrophile (as was demonstrated for the ClCONEt 2 DMG in many of the examples collected in Table 2). If the DMG introduced in this manner is relatively strong, [37] further DoM reactions (step b) to introduce DMG 3 may be possible. The continuation of this first step of walk-around-the-ring anionic chemistry may be envisaged.…”

“…[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] character to these experiments. [37] In that work, we restricted the study to the bare O-phenyl carbamate, methyl-substituted derivatives, and O-naphthyl carbamates. Thus, systems 1 and 3 are unexceptional for metalation products, as indicated by the arrows; meta-DMG system 2 has the beneficial but not completely invariable quality of synergistic metalation between the two DMGs.…”

“…As part of a comprehensive study of the N,N-dialkyl O-carbamate DMG, we reported its DoM chemistry for the general synthesis of ortho-disubstituted derivatives as well as its anionic ortho-Fries rearrangement to obtain salicylamides. [37] In that work, we restricted the study to the bare O-phenyl carbamate, methyl-substituted derivatives, and O-naphthyl carbamates. Herein, we describe the results of a systematic study on the competitive metalation of four DMG-bearing derivatives [DMG = Cl, OMe, OMOM (MOM = methoxymethyl), and CONEt 2 ] in comparison with the OCONEt 2 DMG.…”