Ligand Redox Effects in the Synthesis, Electronic Structure, and Reactivity of an Alkyl−Alkyl Cross-Coupling Catalyst

Abstract

The ability of the terpyridine ligand to stabilize alkyl complexes of nickel has been central in obtaining a fundamental understanding of the key processes involved in alkyl-alkyl cross-coupling reactions. Here, mechanistic studies using isotopically labeled (TMEDA)NiMe(2) (TMEDA = N,N,N',N'-tetramethylethylenediamine) have shown that an important catalyst in alkyl-alkyl cross-coupling reactions, (tpy')NiMe (2b, tpy' = 4,4',4' '-tri-tert-butylterpyridine), is not produced via a mechanism that involves the formation of methyl radicals. Instead, it is proposed that (terpyridine)NiMe complexes arise via a comproportionation reaction between a Ni(II)-dimethyl species and a Ni(0) fragment in solution upon addition of a terpyridine ligand to (TMEDA)NiMe(2). EPR and DFT studies on the paramagnetic (terpyridine)NiMe (2a) both suggest that the unpaired electron resides heavily on the terpyridine ligand and that the proper electronic description of this nickel complex is a Ni(II)-methyl cation bound to a reduced terpyridine ligand. Thus, an important consequence of these results is that alkyl halide reduction by (terpyridine)NiR(alkyl) complexes appears to be substantially ligand based. A comprehensive survey investigating the catalytic reactivity of related ligand derivatives suggests that electronic factors only moderately influence reactivity in the terpyridine-based catalysis and that the most dramatic effects arise from steric and solubility factors.

Unusual Reactivity Patterns of 1,3,6,8-Tetraazatricyclo-[4.4.1.13,8]-dodecane (TATD) Towards Some Reducing Agents: Synthesis of TMEDA

“…This diamine is a versatile bidentate ligand and a chelating Lewis base [7]. Many of these complexes have shown catalytic activity in oxidative coupling reactions [8], olefin polymerizations [9], oxidative carbonylation of phenol to produce diphenyl carbonate (DPC) [10], and alkyl-alkyl cross-coupling reactions [11]. In the same way, TMEDA has been used as an initiator of anionic polymerization in the synthesis of high vinyl copolymers containing styrene and butadiene [12], lithiation by alkylLi/TMEDA [13], reductive ring opening of many oxygen-, nitrogen-, or sulfur-containing heterocycles [14], synthesis of asymmetric hydroborating reagents [15] and diastereoselective dihydroxylation of olefins [16].…”

sp3-sp3 Coupling reactions in the synthesis of natural products and biologically active molecules

“…Fast reductive elimination provides a nickel-complex 7c and product 10. 10 In fact, this mechanistic pathway may explain the excellent stereoconvergence found for asymmetric versions of Negishi alkyl-alkyl cross-coupling reactions (vide supra).…”

“…9 Vicic and co-workers proposed an alternative mechanism for the nickel-catalysed Negishi alkyl-alkyl coupling (Scheme 3). 10 The proposed catalytic cycle begins with the reaction of a (terpyridyl)Ni(alkyl) complex 7, with an alkyl halide (here cyclohexyl iodide) (8) to form complex 7a and alkyl radical 9.…”

Asymmetric Suzuki Cross-Couplings of Activated Secondary Alkyl Electrophiles: Arylations of Racemic α-Chloroamides

“…The moderate ee of the unreacted electrophile even at high conversion could be due to modest differentiation of the enantiomers by the chiral catalyst, or it could result from excellent discrimination, but some reversibility, in the oxidative addition to nickel. 17 In order to gain insight into this issue, we examined the Suzuki arylation of the individual enantiomers of the α-chloroamide (eq 6 and eq 7). For both cross-couplings, the ee of the unreacted electrophile at partial conversion is essentially unchanged, consistent with irreversible oxidative addition under the reaction conditions.…”