Pd(II)-Catalyzed Azine-Assisted Enantioselective Oxidative C–H/C–H Cross-Coupling of Ferrocenes with Various Heteroarenes

Abstract

A palladium­(II)-catalyzed enantioselective oxidative cross-coupling of ferrocenes with heteroarenes is described. Mono-N-protected amino acids can be used as sources of chirality. With azine as an efficient directing group, various substituted planar chiral ferrocenes were obtained via a dual C–H bond activation pathway in medium yields (up to 72%) with good enantioselectivity (up to 89.4:10.6 er) under mild conditions.

Synergic Palladium Catalysis for Aerobic Oxidative Coupling

“…Zhang and co-worker reported the Pd-catalyzed enantioselective oxidative coupling of ferrocenes with heteroarenes containing N, O or S atoms, using mono-N-protected amino acids as chiral ligands (Scheme 9). [74] This work demonstrated the novel utilization of an azine as a directing group for ferrocene to achieve enantioselective CÀ H functionalization and the desired product was generated efficiently under the optimized conditions. [a] Reaction conditions were those presented in Scheme 6c.…”

Ferrocene derivatives with planar chirality and their enantioseparation by liquid‐phase techniques

“…Indeed, the development of advanced computational methods has allowed to recognize that catalysts equipped with large aromatic groups may provide cumulative noncovalent interactions such as C-H⋯π, N-H⋯π and π⋯π with a remarkable stabilization force on the catalytic transition states, often with the participation of dispersion forces [192]. In this frame, in the last few years, the analytical enantioseparation of substituted 4-methyl-6-(methylsulfonyl)-6H-benzo [2,3]azepino[4,5-a]ferrocenes 35a-g (Table 5) [144], of 1-N, N-diisopropyl-2-substituted-ferroceneamides 130 (Figure S9) [193] and of 1-[(2E)-(4-substituted-benzylidene)hydrazono]methyl]-2-substituted-ferrocenes 38 (Figure S9) [147] were reported. As shown in Table 5, for the enantioseparation of planar chiral ferrocenes containing extended π-electronic cloud regions, methylated polysaccharide-based selectors, in particular amylosebased ones, are preferred along with mobile phases featured by low eluting strength.…”

“…The enantioselective alkylation of amidoferrocene with diethylmalonate generated compounds 37 with ee s between 64% and 88% [ 146 ]. A Pd/chiral ligand system was used recently for the double C–H activation of an azine‐based ferrocene to provide heteroaryl functionalized ferrocenes 38 with ee in the range 50%–60% [ 147 ]. As mentioned earlier (see Figure S3 ), the planar chiral aminopyridine derivatives based on the ferrocene ligands developed by Fu have shown excellent enantioselectivity in a wide range of asymmetric reactions [ 100 , 148 ].…”

“…A Pd/chiral ligand system was used recently for the double C–H activation of an azine‐based ferrocene to provide heteroaryl functionalized ferrocenes 38 with ee in the range 50%–60% [ 147 ].…”

Palladium-catalyzed cross-coupling of unreactive C(sp3)–H bonds with azole C(sp2)–H bonds by using bromide as a traceless directing group

“…Owing to the higher dissociation energy, lower acidity, and weaker electronic interaction with palladium, the activation of the C(sp 3 )–H bond usually is much more difficult. 4 Therefore, although rapid advancements have been achieved in the palladium-catalyzed cross-coupling of C(sp 2 )–H/C(sp 2 )–H bonds, 5,6 the progress in similar cross-coupling of C(sp 3 )–H/C(sp 2 )–H bonds has lagged far behind. 4,7 Most reported examples have focused on intramolecular cross-couplings (Scheme 1a).…”