Carbon-heteroatom bond formation catalysed by organometallic complexes

Abstract

At one time the synthetic chemist's last resort, reactions catalysed by transition metals are now the preferred method for synthesizing many types of organic molecule. A recent success in this type of catalysis is the discovery of reactions that form bonds between carbon and heteroatoms (such as nitrogen, oxygen, sulphur, silicon and boron) via complexes of transition metals with amides, alkoxides, thiolates, silyl groups or boryl groups. The development of these catalytic processes has been supported by the discovery of new elementary reactions that occur at metal-heteroatom bonds and by the identification of factors that control these reactions. Together, these findings have led to new synthetic processes that are in daily use and have formed a foundation for the development of processes that are likely to be central to synthetic chemistry in the future.

Figure 1. Catalytic C–C and C–H bond-forming processes

Cross-coupling (a), hydrogenation of olefins (b) and metathesis of olefins (c) are commonly used reactions in organic synthesis. Alkane dehydrogenation (d) has been studied as a means to modify typically unreactive alkanes and has been combined with alkene metathesis to develop a new alkane metathesis. L_n, ancillary ligand; M, metal.

Figure 2. Mechanisms of three common catalytic organometallic processes

a, Cross-coupling is initiated by oxidative addition of an organic halide, continues through transmetallation and terminates by reductive elimination. b, Hydrogenation begins with oxidative addition of the H–H bond in dihydrogen, migratory insertion of an olefin to form a C–H bond and reductive elimination to form a second C–H bond. c, The metathesis of olefins occurs through a series of [2 + 2] cycloadditions and retro [2 + 2] cycloadditions. Ar, aryl.

Figure 3. Recently discovered organometallic reactions of transition-M–heteroatom bonds

a, Reductive elimination to form C–N, C–O and C–S bonds in amines, ethers and thioethers. b, Oxidative addition of amine N–H bonds. c, Migratory insertions of olefins into metal amides and metal alkoxides. d, [2 + 2] Cycloadditions between olefins and M–imido or M–oxo complexes. These reactions are analogues of classic reactions occurring at M–C bonds and have only recently been discovered.

Figure 4. Aspects of palladium-catalysed amination of aryl halides and related reactions

a, The overall transformation in the presence of a palladium (Pd) catalyst. Four generations of ligands (L) have been developed for the catalytic process. The first-generation catalyst contained P(o-tolyl)₃. The second-generation catalysts contained chelating aromatic phosphines as ligand: DPPF (1,1′-bis(diphenylphosphino)ferrocene), BINAP (2,2′-bis(diphenylphosphino)-1,1′-binaphthyl) and xantphos (4,5-bis(diphenyl-phosphino)-9,9-dimethylxanthene). The third-generation catalysts contain hindered alkylphosphines and carbenes: P(t-Bu)₃, Ph₅FcP(t-Bu)₂, N-heterocyclic carbenes, (biaryl)PR₂, (heterobiaryl)PR₂ and caged P(NRR′)₃. The fourth (most recent) generation of catalysts contain hindered ferrocenyl alkyl bisphosphines. b, The catalytic cycle involving oxidative addition of an aryl halide, formation of an arylpalladium amide and reductive elimination of an amine. c, Reactions revealing the electronic effects on reductive elimination to form C–N bonds in amines and amides, and C–O bonds in ethers. The rates of reductive elimination from Pd(II) are faster when the heteroatom bound to the metal is more electron rich. Fc, ferrocenyl; i-Bu, isobutyl; Me, methyl; OTf, trifluoromethanesulphonate; OTs, 4-toluenesulphonate; Ph, phenyl; t-Bu, tert-butyl; tolyl, C₆H₄-4-Me.

Figure 5. Organometallic oxidative C–O and C–halogen bond-forming functionalization of C–H bonds

a, Two representative directed functionalizations. In the upper example, the metal catalyst binds to the nitrogen of the oxazoline substituent, and this binding positions the catalyst for cleavage and functionalization of the ortho C–H bond on the phenyl ring. The combination of the PhI(OAc)₂ oxidant and iodine is thought to lead to an intermediate arylpalladium(IV)–iodide complex, which forms the aryl C–I bond in the product. In the lower example, a related process occurs. In this case, binding of the catalyst to the oxime nitrogen positions it for cleavage of the C–H bond shown. The PhI(OAc)₂ oxidant is then thought to lead to an alkylpalladium(IV) acetate intermediate, which forms the C–O bond in the product. b, General catalytic cycle for palladium-catalysed oxidation of C–H bonds involving cleavage of a C–H bond, oxidation to a high-valent metal centre and reductive elimination to form a C–heteroatom bond. c, Example of the C–X bond-forming step in a well-characterized system. This reaction is thought to model the C–heteroatom bond-forming step of directed C–H-bond functionalizations. Reductive elimination to form the C–O bond on the organic product is followed by coordination of deuterated pyridine solvent. D, deuterium. equiv., equivalents; OAc, acetate.

Figure 6. Summary of the functionalization of alkanes with M–B intermediates

a, The overall transformation. In this process, the rhodium catalyst selectively cleaves the terminal C–H bond of an alkane or of the alkyl group of an acetal, ether, amine or alkyl fluoride, and it delivers a boryl group from the diboron (pinB–Bpin) reagent to the resultant alkyl intermediate to form the functionalized product. b, The catalytic cycle for alkane borylation involves C–H bond cleavage by an M–B intermediate followed by reductive elimination to form a B–C bond. c, The energetics of the reaction coordinate for C–H bond functionalization by M–B complexes deduced by using a density-functional-theory method. This reaction coordinate shows that the p orbital on boron assists in the C–H bond-cleavage step. Cp*, pentamethylcyclo pentadienyl; pin, pinacolate.

Figure 7. Organometallic oxidation and oxidative amination of olefins

a, The overall mechanism for the palladium-catalysed oxidation of olefins. b, c, Mechanisms for the C–heteroatom bond-forming step of the catalytic process. This step can occur by nucleophilic attack on a coordinated olefin (b) or migratory insertion into an M–heteroatom bond (c). β-H elim., β-hydrogen elimination.

Figure 8. Two mechanisms for catalytic hydroaminations of C–C multiple bonds through M–amido intermediates

a, Hydroamination of olefins catalysed by lanthanide–amides occurring by intramolecular insertions of alkenes into an M–amide bond. b, Hydroamination of olefins catalysed by group IV complexes occurring by [2 + 2] cycloaddition to form a metallocyclic amido intermediate. Cp, cyclopentadienyl; La, lanthanide.

Figure 9. Data and basis for relative rates of olefin insertion into alkyl, amide and alkoxo complexes

a, b, Examples of insertions into late-transition-metal–alkoxo and –amido complexes. c, Rationalization for why the rates of olefin insertion into late-transition-metal alkoxides and amides are faster than into late-transition-metal alkyls, based on the destabilization of the alkoxo and amide reactants and the stabilization of the products of insertion into the alkoxo and amido complexes by an M–Y dative bond. Et, ethyl.