NONORGANOMETALLIC PATHWAY OF THE PASSERINI REACTION ASSISTED BY TITANIUM TETRACHLORIDE

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 alpha-hydroxy amides. In order to clarify the mechanism of the reaction, we have isolated TiCl4-RNC and TiCl4-R2CO adducts, {2,6-Me2C6H3NC)TiCl3]2(mu-Cl)2}2, 2, [TiCl4{mu2-CO=C(OEt)CH2NC}]2, 3, [TiCl4{mu2-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(eta3-OC(Mes)(H)C(Cl)=NCH2C(OEt)=O], 6, [mer-TiCl3(eta3-OC(Ph)(Me)C(Cl)=NCH2C(OEt)=O], 7, [mer-TiCl3(eta3-OC(Ph)(Me)C(Cl)=NCH2P(OEt)2=O], 10, and [mer-TiCl3(eta3-OC(Ph)(OCPh)C(Cl)=NCH2C(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 alpha-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 P2(1)/n, a = 13.943(1) angstrom, b = 8.045(1) angstrom, c = 12.141(1) angstrom, alpha = gamma = 90-degrees, beta = 104.76(1)degrees, Z = 2, R = 0.048; 4 is monoclinic, space group P2(1)/c, a = 12.961(1) angstrom, b = 11.770(1) angstrom, c = 10.917(1) angstrom, alpha = gamma = 90-degrees, beta = 114.13(1)degrees, Z = 2, R = 0.049; 5 is triclinic, space group P1BAR, a = 10.549(1) angstrom, b = 10.668(1) angstrom, c = 9.533(1) angstrom, alpha = 115.08(1)degrees, beta = 115.47(1)degrees, gamma = 95.01(1)degrees, Z = 2, R = 0.035; 7 is triclinic, space group P1BAR, a = 9.731(2) angstrom, b = 10.552(3) angstrom, c = 8.978(2) angstrom, alpha = 96.66(2)degrees, beta = 101.86(2)degrees, gamma = 95.30(2)degrees, Z = 2, R = 0.042; 10 is monoclinic, space group P2(1)/c, a = 11.503(2) angstrom, b = 14.095(2) angstrom, c = 15.110(2) angstrom, alpha = gamma = 90-degrees, beta = 96.79(2)degrees, Z = 4, R = 0.116; 12 is triclinic, space group P1BAR, a = 9.272(4) angstrom, b = 9.965(4) angstrom, c = 15.029(6) angstrom, alpha = 101.84(3)degrees, beta = 104.12(3)degrees, gamma = 99.53(3)degrees, Z = 2, R = 0.092.