Hydrophosphination

Hydrophosphination is the addition of a phosphorus-hydrogen bond across a carbon-carbon multiple bond (Scheme 1) forming a new phosphorus-carbon bond. Hydrophosphination has a high atom economy. Hydrophosphination is the addition of a phosphorus-hydrogen bond across a carbon-carbon multiple bond (Scheme 1) forming a new phosphorus-carbon bond. Hydrophosphination has a high atom economy. Like other metal-catalyzed heterofunctionalizations, addition of an E-H bond to an unsaturated substrate, a problem is encountered when E is a donor (hydroamination, hydration, hydrothiolation) because the product phosphines can poison the catalyst. Another consideration is that the P-H addition to a carbon-carbon multiple bond can occur in a variety of different ways. The selectivity of the addition is influenced by the catalyst. A variety of routes exist for the synthesis of phosphines without a catalyst, e.g. using radical, thermal, photochemical. Ultraviolet irradiation or conventional free-radical sources initiate radical hydrophosphinations. H-atom abstraction from P-H bond produces the phosphino radical, a seven electron species (Scheme 2). Phosphines with more than one P-H bond can react more than once to form the tertiary phosphines. The steps proposed for metal-catalyzed hydrophosphinations typically include coordination of the primary or secondary phosphine to the metal, activation of the P-H bond (via oxidative addition or proton abstraction by an external base), P-C bond formation (through either insertion, Michael addition, or cycloaddition), reductive elimination or addition of the abstracted proton and finally substitution of the newly made phosphine by the starting primary or secondary phosphine. Most early metal hydrophosphination catalysts are electron-deficient, d0 metal complexes. Catalysis typically involves inner-sphere P-C bond forming through metal-phosphido intermediates due to the nucleophilicity of the phosphido, being polarized by the metal. Hydrophosphination of simple alkenes and alkynes is catalyzed by lanthanocene complexes. The catalytic cycle for the hydrophosphination of α,ω-pentenylphosphine is shown in Scheme 3. Typical of most electron-poor early metal catalysts for hydrophosphination, this one includes the characteristic P-H bond cleavage and P-C and C-H bond formation steps. The primary phosphine undergoes a σ-bond metathesis with the bis(trimethylsilyl)methylene ligand forming the lanthanide-phosphido. This is then followed by a 1,2-insertion of the pendant terminal alkene or alkyne on the phosphine into the Ln-P bond. Finally, protonolysis of the Ln-C bond with the starting primary phosphine releases the new phosphine and regenerates the catalyst. Given that the metal is electron-poor, the M-C bond is polar enough to be protonolyzed by the substrate primary phosphine; this is characteristic of electron-poor, early metals. Since many of the transition metal catalysts that are involved in hydrophosphination employ a phosphido intermediate, it is surprising that there are so few examples of catalysts that involve the metal-phosphinidene intermediate, M=PR. One such example is the Ti-catalyzed hydrophosphination of diphenylacetylene with phenylphosphine (Scheme 4) by Mindiola et al. This system involves a cationic catalyst precursor that is stabilized by the bulky 2,4,6-tri(isopropyl)phenyl- substituent on the phosphinidene and the close ionic association of methyltris(pentafluorophenyl)borate. This precursor undergoes exchange with phenylphosphine to make the titanium-phenylphosphinidene complex which is the catalyst. The Ti=PPh undergoes a cycloaddition with diphenylacetylene to make the corresponding metallacyclobutene. The substrate, phenylphosphine, protonolyzes the Ti-C bond and after a proton shift regenerates the catalyst and releases the new phosphine. Titanium-catalyzed 1,4-hydrophosphination of 1,3-dienes with diphenylphosphine has been demonstrated (Scheme 5). It is a rare example of a non-d0 early transition metal catalyst that catalyzes hydrophosphination. In the first step, the Ti2+ precursor undergoes an oxidative addition of the P-H bond in diphenylphosphine which generates the Ti3+ catalyst. The rest of the catalysis involve the usual steps: P-C bond formation via 1,2-insertion followed by C-H bond formation and P-H bond activation via protonolysis with the substrate secondary phosphine.