A wide mechanistic spectrum observed in three different reactions with organometallic reagents

Abstract

The halogen–lithium exchange reaction is of one of the most powerful method for the preparation of organolithium compounds, but its mechanism is still controversial. To afford some new elements, we synthesized a new suitable fast radical clock, bearing a phenyl group at the alkene C‐terminal. The examination of some mechanistic clues, as well as the identification of the unexpected by‐products allowed the conclusion that the reaction proceeds by a polar mechanism and no evidence for radicals were found. The second reaction discussed is the insertion of NO in the NLi bond of lithium amides. Evidence for the involving of paramagnetic and nitrosonium intermediates, as well as equilibria between different reactive species were essential for the proposal of a whole complex mechanism, which was confirmed by theoretical calculations. Finally, results on the addition of heteroaromatic organocuprates to α,β‐unsaturated substrates are presented. Several reaction conditions were looked for to lead the reaction toward the more interesting 1,4‐conjugated addition. Thus, addition of up to 6 equivalents of TMSCl to the reaction with arylcuprates leads to a clean addition yielding more than 95% of the 1,4‐addition product. A further objective of the paper is to show how the search of unexpected routes of reaction allowed developing original pathways to lead them toward the formation of appealing functionalized compounds. Copyright © 2010 John Wiley & Sons, Ltd.

Intramolecular carbolithiation‐cyclization‐electrophilic substitution: solvent effect and mechanistic study

“…In a previous work, our group proved that the reaction of 1 with n ‐BuLi in tetrahydrofuran (THF), yielding products 2 , 3 , and 4 , occurs via a polar rather than a radical mechanism Scheme .…”

“…Cumarans (2,3‐dihydrobenzofuran) had a basic skeleton found in a number of biologically interesting compounds, like the neolignans . Attempts to build this skeleton by using 2‐bromophenyl‐( E )‐2‐propenyl ether failed due to γ‐elimination, but we showed that, by using 2‐bromophenyl‐3‐phenylprop‐2‐enyl ether, followed by intramolecular carbolithiation and trapping of the new lithiated cyclic intermediate, 3‐substituted 2,3‐dihydrobenzofurans could be obtained . Previous works seemed to show that the product distribution was quite sensitive to the solvent; therefore, the present study firstly focus on the solvent effects.…”

“…[11] Attempts to build this skeleton by using 2-bromophenyl-(E)-2-propenyl ether failed due to γ-elimination, [12] but we showed that, by using 2-bromophenyl-3-phenylprop-2-enyl ether, followed by intramolecular carbolithiation and trapping of the new lithiated cyclic intermediate, 3-substituted 2,3-dihydrobenzofurans could be obtained. [13] Previous works [14,15] seemed to show that the product distribution was quite sensitive to the solvent; therefore, the present study firstly focus on the solvent effects. On the other hand, an unexpected high diastereoselectivity was observed in the intramolecular carbolithiation-electrophilic substitution tandem sequence.…”

Is Carbon Dioxide Able to Activate Halogen/Lithium Exchange?

“…At first, we analyzed the reactions with monomeric t BuLi(THF) 3 and t BuLi(CO 2 ) 3 species as lithiating agents. The reactions proceed through polar substitution of the nucleophile at the halogen atom 57–62…”

Computational Perspectives on Organolithiums

“…Nudelman and coworkers [119] have, for example, computationally studied NO insertion reactions generating nitrosamines. Another example is the work done by Anders and coworkers [67], who inserted CO 2 into the N-Li bond of chiral lithium amides to generate chiral lithium carbamates.…”