Carbon−Heteroatom Bond-Forming Reductive Eliminations of Amines, Ethers, and Sulfides

Abstract

Elementary transition metal-mediated reactions that form and cleave the bonds of organic molecules are the foundation of homogeneous catalysis. Such bond cleavage and formation often occurs by oxidative addition and reductive elimination. As shown in Scheme 1, these two reactions are essentially the same process in opposite directions: oxidative addition increases the oxidation state of the metal by two, decreases the d-electron count by two, and increases the overall number of valence electrons by two, while reductive elimination inflicts the opposite two-electron changes. Thermodynamic factors dictate whether a complex will undergo elimination or addition.The formation of carbon-hydrogen and carboncarbon bonds by reductive elimination is now common. Catalytic hydrogenation of alkenes, hydroformylation, alkene arylation (Heck reaction), and cross-coupling processes all involve C-H and C-C bond-forming reductive eliminations. The formation of carbon-heteroatom bonds by reductive elimination is less common, and just five years ago reductive elimination reactions that form C-O, C-N, and C-S bonds in ethers, amines, and sulfides had not been observed directly. It was unclear whether a kinetic barrier prevented these classes of reductive elimination, whether these eliminations were disfavored thermodynamically, or whether appropriate compounds to observe these reactions simply had not been prepared.During the past five years, palladium-catalyzed chemistry that produces arylamines from aryl halides and either primary or secondary amines has been developed, 1-4 and a catalytic cycle that is supported by detailed mechanistic studies 5 is provided in Scheme 2. It seemed likely that the amination process, first reported with tin amides by Kosugi and Migita over 10 years ago, 6,7 involved reductive elimination of amine. It, therefore, seemed to the members of my research group that the generation of stable palladium amido aryl complexes would allow for the direct observation of C-N bond-forming reductive elimination of amines.In addition, similar palladium-and nickel-catalyzed reactions that form aryl sulfides have been reported, [8][9][10][11][12][13][14] and again, generation of stable thiolato aryl complexes would allow for the direct observation of C-S bondforming reductive elimination of sulfides. Information on how these reactions occur might lead to improvements upon the catalytic formation of amines and sulfides. Finally, these studies may reveal systems that would undergo reductive elimination chemistry to form the C-O bonds in aryl ethers. As a result of this work, palladiumand nickel-catalyzed amination of aryl halides has become a general process 1-4 and new chemistry that forms aryl ethers has been developed recently. [15][16][17][18][19] Reviews of the catalytic carbon-heteroatom bond-forming coupling processes have been published recently. [20][21][22] This Account describes work in my laboratory, along with related work from other groups, on the discovery of complexes that reductively eliminate amines, ethe...

Combined DFT and experimental studies of C–C and C–X elimination reactions promoted by a chelating phosphine–alkene ligand: the key role of penta-coordinate PdII

“…14 Thus, it was important to probe the potential role of simply the olefinic moiety of L1 in promoting reductive elimination rather than the phosphine-alkene ligand as a whole. Consequently, the coordination chemistry of the related phosphine-alkane derivative This complex then isomerises cleanly to the trans-diphosphine complex within 24 h at r.t; no further reaction of trans-[PdMe 2 (κ 1 -P-L2) 2 ] is observed even in the presence of excess L2 at 60 ºC. 22 Although these observations suggest that κ 2 -P,C chelation is vital in retaining the cisdialkyl geometry for reductive elimination, it remains unclear whether the coordination of the olefinic moiety of L1 also plays an electronic role in promoting reductive elimination.…”

“…(1') and the transition state TS 1'→2 together with those of the tetra-coordinate complex cis-[PdMe 2 (4)) and corresponding transition states TS 3'→2 , TS 3→2 , TS 4→2 . Selected bond distances (in Å) and bond angles (in degrees).…”

“…18 This is particularly surprising since a host of experimental studies have been described in these areas. 2,5,19 Once again, as is the case for palladium-mediated C-C bond formation, analogous processes for the formation of Cheteroatom bonds are also subject to significant effects imposed by the steric and electronic characteristics of both the coupling partners and ancillary ligands. 6 An important strategy for enhancing the rates of reductive elimination during palladium-mediated C-E bond-forming reactions (E= C, halide, heteroatom) is the use of chelating ligands.…”

Enantioselective organocatalytic construction of pyrroloindolines by a cascade addition–cyclization strategy: Synthesis of (–)-flustramine B

“…As revealed in entry 6, we have successfully used electron-deficient nucleophiles in the context of a 6-bromo-substituted tryptamine (86% yield, 97% ee, 31:1 dr). Such halogenated indole adducts should prove to be valuable synthons for use in conjunction with organometallic technologies [e.g., Buchwald-Hartwig (55,56) and Stille couplings (57)]. The capacity of 6-bromotryptamine derivatives to participate in this process has direct implications for the synthesis of 6-bromopyrroloindoline natural products such as flustramine B (see below).…”

Palladium-catalysed amination of 2-acyl-1-alkyl-5-bromopyrroles

“…Although palladium-catalysed carbon-nitrogen bond formation using aryl halides has been extensively investigated in recent years, [5][6][7][8] allowing the coupling of a great variety of amines with any halobenzene or haloazine, no broadly applicable methodology had been developed to prepare five-membered heterocycles 9;10 until very recently when Hartwig reported the successful amination of halofurans, -thiophenes, -thiazoles, -oxazoles, -indoles and -benzimidazoles. 11 However, the methodology was not extended to halopyrroles because of the instability of these substrates.…”