Preparation of Tri- and Tetrasubstituted Allenes via Regioselective Lateral Metalation of Benzylic (Trimethylsilyl)alkynes Using TMPZnCl·LiCl

Abstract

The zincation of various 1-(trimethylsilyl)-3-aryl-1-propynes with TMPZnCl·LiCl followed by a Pd-catalyzed coupling with aryl halides provides arylated allenes in 52-92% yield. Subsequent metalation with TMPZnCl·LiCl and cross-coupling with a second different aryl halide provides regioselectively tetrasubstituted allenes in 42-70% yield. This sequence can be performed in a one-pot procedure. DFT calculations and NMR studies support the formation of allenylzinc and propargyllithium intermediates starting from 1-(trimethylsilyl)-3-phenyl-1-propyne.

Regioselective Transition‐Metal‐Free Allyl–Allyl Cross‐Couplings

“…In line with this rationalization we find that hetero dimers of type 8 represent the most stable structures in solution; this is indicated by the significant exergonicity of the exchange reaction of (LiCl) 2 (sol) 4 with (RZnBr) 2 (sol) 2 (Δ G sol (THF)=−14.4 kJ mol −1 , Δ G sol (DMPU)=−27.1 kJ mol −1 ) at the B2PLYP‐D3(FC)/def2‐TZVPP level including implicit SMD/B3LYP/6‐31G(d) solvation . Indeed, 1 H and 13 C NMR shifts in THF obtained during the LiCl‐mediated oxidative addition of zinc to the carbon–bromine bond of prenyl bromide ( 2 b ) correlate quite well with theoretically calculated chemical shifts of lithium zinc dimer 8‐THF at the mPW1K/IGLO‐III level of theory (see the Supporting Information). Substituted allylic organometallics often show high diastereoselectivity in reactions with electrophiles due to their rather ordered cyclic or acyclic transition states .…”

“…[17] Thea ddition of LiCl is currently believed to accelerate reactions of organometallic reagents through increased formation of monomeric species or ate-like complexes. [20] Indeed, 1 Ha nd 13 CNMR shifts in THF obtained during the LiCl-mediated oxidative addition of zinc to the carbon-bromine bond of prenyl bromide (2b)c orrelate quite well with theoretically calculated chemical shifts of lithium zinc dimer 8-THF at the mPW1K/IGLO-III level of theory [21] (see the Supporting Information). [20] Indeed, 1 Ha nd 13 CNMR shifts in THF obtained during the LiCl-mediated oxidative addition of zinc to the carbon-bromine bond of prenyl bromide (2b)c orrelate quite well with theoretically calculated chemical shifts of lithium zinc dimer 8-THF at the mPW1K/IGLO-III level of theory [21] (see the Supporting Information).…”

A Predictive Model Towards Site‐Selective Metalations of Functionalized Heterocycles, Arenes, Olefins, and Alkanes using TMPZnCl⋅LiCl

“…1h), the zincated alkenes and allenes 10 a-f were obtained in 65-95 %y ield. [41,42] To ensure that these vertical deprotonation energies are representative for the full study,t he respective energies for all other structures were calculated as well (see Supporting Information). Interestingly,t he prediction fidelity of Approach 2 (vertical deprotonation) is closely similar (> 80 %) as compared to that of Approach 1 (relaxed deprotonation).…”

A Predictive Model Towards Site‐Selective Metalations of Functionalized Heterocycles, Arenes, Olefins, and Alkanes using TMPZnCl⋅LiCl

“…Forschungsartikel 1h), the zincated alkenes and allenes 10 a-f were obtained in 65-95 %y ield. [41,42] To ensure that these vertical deprotonation energies are representative for the full study,t he respective energies for all other structures were calculated as well (see Supporting Information). Interestingly,t he prediction fidelity of Approach 2 (vertical deprotonation) is closely similar (> 80 %) as compared to that of Approach 1 (relaxed deprotonation).…”