Figure 6: Proposed mechanistic paths for the ligand-controlled regioselective S–M cross-coupling of heterocyclic allylic boronates 3 and 4. | Nature Communications

Figure 6: Proposed mechanistic paths for the ligand-controlled regioselective S–M cross-coupling of heterocyclic allylic boronates 3 and 4.

From: Synthesis of chiral heterocycles by ligand-controlled regiodivergent and enantiospecific Suzuki Miyaura cross-coupling

Figure 6

(a) Use of different ligands leads to a mechanistic divergence where the NHC catalyst Pd-PEPPSI-iPr is alleged to promote a syn-SE transmetallation and a fast reductive elimination to the α coupling product (4-substituted). It is hypothesized that phosphine ligands XPhos and (4-CF3-C6H4)3P promote a syn-SE′ mechanism that can lead to both isomers depending on the rate of reductive elimination of intermediate B. Fast reductive elimination with XPhos (KRE>Kσ-π) leads to the γ regioisomers, whereas slower reductive elimination with (4-CF3-C6H4)3P allows isomerization (Kσ-π>KRE) to the thermodynamically favoured σ complex D affording the α coupling product. (b) Control experiment showing that only the NHC catalyst Pd-PEPPSI-iPr is competent in the coupling with the non-heteroatom-conjugated allylboronate 41, which supports the requirement for a strong π-donating alkene as found in the heteroatom-conjugated substrates 3 and 4, and a SE′ transmetallation with the phosphines XPhos and (4-CF3-C6H4)3P. Ar=(4-CF3-C6H4)3P.

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