Intramolecular Carbolithiation of Heterosubstituted Alkynes: An Experimental and Theoretical Study

Abstract

A series of heterosubstitued alkynes was successfully submitted to the intramolecular carbolithiation of their triple bond. We show that the addition is stereoselective because of the control exerted by the terminal substituent X on the geometry of the transition state. A complementary DFT study suggests that the addition is anti when a strong Li-X interaction occurs.

Cobalt-Catalyzed Carbozincation of Ynamides

“…Then, it can be envisioned as follows: (i) insertion of the ynamide 1 into an arylcobalt species A generated from the cobalt precatalyst and the arylzinc reagent; (ii) transmetalation between C and the arylzinc reagent 2 to afford an ortho- alkenylarylzinc intermediate and regenerate the arylcobalt species. The good regio- and stereoselectivity observed are both explained by an oxygen syn directed carbometalation of the ynamide 1 with cobalt species leading to the α-alkenylcobalt intermediate C with the regioselectivity shown, thus overriding the intrinsic polarity of ynamides . It should be pointed out that the intermediate D was then spontaneously quenched leading to the observed syn adduct 3 .…”

Continuous synthesis of 1‐ethoxy‐2,3‐difluoro‐4‐iodo‐benzene in a microreactor system and the Gaussian and computational fluid dynamics simulations

“…In this work, based on similar reactions in the literature, 2,39,40 we empirically assume that the ortho‐lithiation of ED is an elementary reaction, as shown in Figure 7. According to the law of mass action, the reaction order of the two reactants has been determined to be 1.…”

IntramolecularAnti‐Carbolithiation of Alkynes: Stereo‐Directing Effect of Lithium‐Coordinating Substituents

“…Previous computational studies on intramolecular carbolithiation support the involvement of a tetracoordinated lithium atom chelated with two solvent ligands. [16][17][18]23,76,77] Accordingly, we performed the calculations on the basis of monomeric aryllithiums with two explicit Me 2 O molecules.…”

“…[13][14][15] DFT calculations revealed that the anti-carbolithiation mechanism was triggered by a strong coordination of the lithium to the heteroatom at the alkyne terminus. [16][17][18] A few examples of anti-addition of alkyllithiums onto triple bonds have also been sporadically reported, however factors explaining these unexpected stereoselectivities have not yet been clearly identified. [19][20][21] In the course of our ongoing studies on the formation of carbocycles via intramolecular carbolithiation, [22,23] we took an interest in the 5-exodig cyclization of o-homopropargyl aryllithiums.…”

“…demonstrated that the intramolecular carbolithiation of some heterosubstituted alkynes resulted solely in the E ‐isomer (Scheme 1). [13–15] DFT calculations revealed that the anti ‐carbolithiation mechanism was triggered by a strong coordination of the lithium to the heteroatom at the alkyne terminus [16–18] . A few examples of anti ‐addition of alkyllithiums onto triple bonds have also been sporadically reported, however factors explaining these unexpected stereoselectivities have not yet been clearly identified [19–21] .…”