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. 2022 Jan 14;27(2):525.
doi: 10.3390/molecules27020525.

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

Claudia Feberero  1 , Cintia Virumbrales  1 , Carlos Sedano  1 , Lorena Renedo  1 , Samuel Suárez-Pantiga  1 , Roberto Sanz  1
Affiliations

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

Claudia Feberero et al. Molecules. .

Abstract

A straightforward and transition metal-free one-pot protocol to synthesize halobenzo[b]furans has been developed employing simple and easily available starting materials such as O-aryl carbamates and alkynylsulfones. The fine-tuning of the different steps involved was key to achieving a successful one-pot procedure. Initially, a directed ortho-lithiation process, which uses the carbamate as the directed metalation group, was crucial in providing access to O-2-alkynylaryl N,N-diethyl carbamates by a direct alkynylation of the o-lithiated carbamate, with arylsulfonylalkynes as electrophilic reagents. Cyclization of the generated o-alkynylaryl carbamates was successfully accomplished through a strategy involving in situ carbamate alkaline hydrolysis under conventional heating or microwave irradiation, coupled with a subsequent heterocyclization step delivering the desired benzo[b]furans. A wide variety of new halobenzo[b]furans has been synthesized and their utility has been demonstrated by their further transformation.

Keywords: alkynylation; benzo[b]furans; carbamates; cyclization; o-lithiation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
(A) Our previous work. (B) Selective o-lithiation of O-dihalophenyl-N,N-diethylcarbamates. (C) Proposed retrosynthesis for dihalobenzo[b]furans [17,18].
Scheme 2
Scheme 2
(A) Truce reaction developed by Alemán and García-Ruano. (B) Synthesis of O-2-alkynylaryl N,N-diethyl carbamate 2aa [27,28].
Scheme 3
Scheme 3
Preliminary results for the hydrolysis–cyclization of carbamates 2aa and 2da.
Scheme 4
Scheme 4
Synthesis of 3-alkynylsalicylamides 5.
Scheme 5
Scheme 5
Synthesis of o,o′-dialkynyl carbamates 7.
Scheme 6
Scheme 6
Further transformations of benzofuran 3ka.
See this image and copyright information in PMC

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