Intramolecular Substitution Reaction of Alkylidene-Lithium Carbenoids: Regioselective Synthesis of Indenes

Abstract

Intramolecular substitution reaction of geminal dibromo alkenes proceeds to afford indenes, dihydronaphthalenes, dihydrofurans, and dihydropyran via in situ generated lithium alkylidene carbenoids, which have a carbon or oxygen nucleophilic moiety. This reaction provides a regioselective method for the preparation of polysubstituted indenes.

Theoretical Study on the Lithium−Halogen Exchange Reaction of 1,1-Dihaloalkenes with Methyllithium and the Nucleophilic Substitution Reaction of the Resulting α-Halo Alkenyllithiums

“…Although the activation energy of the cyclization of 10a and 10b is lower than that of 10c , the structures 10a and 10b are much less stable than 10c . Accordingly, the cyclization seems to proceed mainly through 10c especially in a less polar solvent such as toluene, which is used in the experiment as a solvent …”

“…However, the inversion ratio is low and electron-transfer processes cannot be excluded. Narasaka and co-workers studied the intramolecular substitution reactions of α-halo alkenyllithium compounds in detail (eq 3). , Their experiments excluded not only electron-transfer processes, but also the carbene insertion, addition−elimination, and allylic rearrangement for a major reaction pathway. On the basis of their results, the cyclization seems mostly to proceed by the in-plain S N 2-type mechanism …”

“…To better understand these intramolecular substitution reactions of α-halo alkenyllithium compounds, we have studied the reaction mechanism computationally. A part of our theoretical study of this intramolecular substitution reaction has been published 16b 1 …”

Concerted Nucleophilic Substitution Reactions at Vinylic Carbons

“…We chose gem-dibromoalkenols as model compounds to examine the substitution reaction of lithium carbenoids (Scheme 7). 10,11 It was envisaged that alkylidene carbenoids A would be generated from dibromoalkenols 1 on treatment with an alkyllithium via lithium-bromine exchange. 12 Substitution of the bromine with the intramolec-ular alkoxy moiety would proceed at the carbenoid center to afford alkenyllithiums B, which would be protonated finally to give cyclic alkenyl ethers 2.…”

Organodilithium Intermediates as Useful Dianionic Synthons: Recent Advances

“…intermediates 94 undergo an intramolecular substitution reaction to give alkenyllithium compounds 95 and LiBr (Scheme 23) [53].…”