Regio- and Stereoselective Synthesis of Ferrocene-Containing β-Iodoallylic Esters and Ethers from the Iodofunctionalization of Ferrocenylallene with Carboxylic Acids, Phenols, and Alcohols

Abstract

The iodofunctionalization of ferrocenylallene with carboxylic acids, phenols, and alcohols is described. The reaction proceeds smoothly in the presence of molecule iodine as a halonium promoter and using various carboxylic acids, phenols, and alcohols as nucleophiles to give the corresponding ferrocene-containing β-iodoallylic ester and ether products in moderate to high yields and with high regio- and stereoselectivities. It can be envisaged that the regio- and stereoselectivity of this reaction may be controlled by the steric effect of the bulky ferrocene group. The presence of the C-I bond in the corresponding products makes these molecules highly attractive from a synthetic point of view, as it provides an opportunity for further transformations. Thus, palladium-catalyzed Heck coupling, Suzuki coupling, Sonogashira coupling, and copper-catalyzed click reactions were carried out successfully.

Regio- and Stereoselective Iodoamination of Ferrocene-Containing Allenylphosphonates: Synthesis of Multifunctional Tetrasubstituted Allylic Amines and Allylic Azides

“…(E)-Dimethyl [3-ferrocenyl-3-benzenamino-2-iodo-1-(4chlorophenyl)propenyl]phosphonate ((E)-5h). Pale yellow solid; 56 mg, 42% yield; R f = 0.42 (petroleum ether/ethyl acetate = 5:1); mp: 154−155 °C; IR (neat, cm −1 ) 3383,1596,1489,1312,1232,1047,821,748,706,563,493; 1 H NMR (500 MHz, CDCl 3 ) δ 7.31−7.24 (m, 4H), 6.97 (dd, J = 25.2, 8.0 Hz, 3H), 6.80 (dt, J = 8.6, 4.8 Hz, 2H), 6.47 (s, 1H), 4.51 (d, J = 0.9 Hz, 1H), 4.43 (s, 1H), 4.37 (d,J = 15.8 Hz,1H),4.25 (d,J = 7.6 Hz,5H),4.21 (s,2H),3.72 (dd,J = 11.3,5.4 Hz, 6H); 13 C{ 1 H} NMR (125 MHz, CDCl 3 ) δ 148. 4,146.1,141.7 (d,J pc = 6.8 Hz),137.9,136.7,135.4,134.1,130.2 (d,J pc = 16.1 Hz),129.3,128.6 (d,J pc = 7.3 Hz),118.7,116.9,114.9,89.9,69.2 (d,J pc = 2.8 Hz),68.1,67.9,67.4,66.3,56.6 (d,J pc = 4.3 Hz), 52.9 (dd, J pc = 18.2, 6.4 Hz); HRMS (ESI) m/z: [M] + calcd for C 27 H 26 ClFeINO 3 P,660.9728;found,660.9745.…”

“…(E)-Dimethyl [3-ferrocenyl-3-benzenamino-2-iodo-1-(4bromophenyl)propenyl]phosphonate ((E)-5i). Pale yellow solid; 58 mg, 41% yield; R f = 0.43 (petroleum ether/ethyl acetate = 5:1); mp: 118−120 °C; IR (neat, cm −1 ) 3378,1591,1492,1305,1232,1185,1044,818,753,688,561,493; 1 H NMR (500 MHz, CDCl 3 ) δ 7.57− 7.33 (m, 3H), 7.32−7.21 (m, 2H), 6.99 (d,J = 7.6 Hz,1H),4H),6.44 (s,1H),4.52 (s,1H),4.44 (s,1H),4.26 (d,J = 11.3 Hz,5H),4.22 (s,2H),3.72 (dd,J = 11.3,5.0 Hz, 6H); 13 C{ 1 H} NMR (125 MHz, CDCl 3 ) δ 146. 1,142.2,137.9,136.7,135.4,131.6 (d,J pc = 7.3 Hz),130.5 (d,J pc = 17.4 Hz),129.3,122.3,118.7,116.9,114.9,69.4 (d,J pc = 10.0 Hz),68.3,67.9,67.6,66.4 (d,J pc = 25.3 Hz),56.7,53.1 (t,J pc = 6.3 Hz); HRMS (ESI) m/z: [M] + calcd for C 27 H 26…”

“…13 C{ 1 H} NMR (125 MHz, DMSO) δ 142. 5,141.0,139.8,138.0,134.5 (d,J pc = 19.2 Hz),130.1,126.6,126.0,100.0,87.6,69.5,69.0,67.8 (d,J (E)-Dimethyl [3-ferrocenyl-3-azido-2-iodo-1-(4-fluorophenyl)propenyl]phosphonate ((E)-6i). Yellow solid; 88 mg, 74% yield; R f = 0.45 (petroleum ether/ethyl acetate = 3:1); mp 124 °C.…”

“…On the other hand, since its discovery in 1951 by Kealy and Pauson, 5 ferrocene and its derivatives have attracted considerable attention from organic chemists for their unique structural features and interesting chemical and biological properties. 6 It is also found that some specially designed molecules containing ferrocene are valuable candidates for antimalarial or anticancer therapies in the field of medical research.…”