Nonorganometallic pathway of the Passerini reaction assisted by titanium tetrachloride

Article abstract of DOI:10.1021/om00031a047

The Passerini reaction assisted by TiCl₄ is a three component reaction (RNC, R′₂CO, TiCl₄) leading to C-C bond formation between the carbonyl and the isonitrile groups, and the formation of α-hydroxy amides. In order to clarify the mechanism of the reaction, we have isolated TiCl₄RNC and TiCl₄-R₂CO adducts, {2,6-Me₂C₆H₃NC)TiCl₃] ₂(μ-Cl)₂}₂> 2, [TiCl₄{μ₂-CO=C(OEt)CH₂NC}]₂, 3, [TiCl₄{μ₂-O=P(OEt)₂CH₂NC}] ₂, 4, and [TiCl₄{PhC(O)-C(O)Ph}], 5. Spectroscopic and X-ray analysis on 2 and 3 ruled out any insertion of the isocyanide into Ti-Cl bonds, as required by the accepted mechanism of this reaction. The reaction on the ketone- or isocyanide-TiCl₄ adducts with the third component of the Passerini reaction led us to the isolation and full characterization of [mer-TiCl₃(η³-OC(Mes)(H)C(Cl)=NCH ₂C(OEt)=O], 6, [mer-TiCl₃(η³-OC(Ph)(Me)C(Cl)=NCH ₂C(OEt)=O], 7, [mer-TiCl₃(n³-OC(Ph)(Me)C(Cl)=NCH₂P(OEt) ₂=O], 10, and [mer-TiCl₃(η³-OC(Ph)(OCPh)C(Cl)=NCH ₂C(OEt)=O], 12, derived from the reaction of MesCHO and PhCOMe with EtOOCCH₂NC, of PhCOCH₃ with O=P(OEt)₂CH₂NC, and PhCOCOPh with EtOOCH₂NC, respectively. These are high yield reactions and form, as imposed by the planar assembled ligand, the mer-isomer only. The hydrolysis of 6, 7, 10, and 12 gave the expected α-hydroxy amide derivatives, 8, 9, 11, and 13, respectively. The overall mechanism of the TiCl₄-assisted Passerini reaction can be described as the electrophilic activation of a carbonyl group by TiCl₄ followed by the nucleophilic attack on the carbonylic carbon by the RNC nucleophile. Crystallographic details: 2 is monoclinic, space group P2₁/n, a = 13.943(1) A?, b = 8.045(1) A?, c = 12.141(1) A?, α = γ = 90°, β = 104.76(1)°, Z = 2, R = 0.048; 4 is monoclinic, space group P2₁/c, a = 12.961(1) A?, b = 11.770(1) A?, c = 10.917(1) A?, α = γ = 90°, β = 114.13(1)°, Z = 2, R = 0.049; 5 is triclinic, space group P1, a = 10.549(1) A?, b = 10.668(1) A?, c = 9.533(1) A?, α = 115.08(1)°, β = 115.47(1)°, γ = 95.01(1)°, Z = 2, R = 0.035; 7 is triclinic, space group P1, a = 9.731(2) A?, b = 10.552(3) A?, c = 8.978(2) A?, α = 96.66(2)°, β = 101.86(2)°, γ = 95.30(2)°, Z = 2, R = 0.042; 10 is monoclinic, space group P2₁/c, a = 11.503(2) A?, b = 14.095(2) A?, c = 15.110(2) A?, α = γ = 90°, β = 96.79(2)°, Z = 4, R = 0.116; 12 is triclinic, space group P1, a = 9.272(4) A?, b = 9.965(4) A?, c = 15.029(6) A?, α = 101.84(3)°, β = 104.12(3)°, γ = 99.53(3)°, Z = 2, R = 0.092.