Highly Active Platinum Catalysts for Nitrile and Cyanohydrin Hydration: Catalyst Design and Ligand Screening via High-Throughput Techniques

Abstract

Nitrile hydration provides access to amides that are indispensable to researchers in chemical and pharmaceutical industries. Prohibiting the use of this venerable reaction, however, are 1) the dearth of biphasic catalysts that can effectively hydrate nitriles at ambient temperatures with high turnover numbers, and 2) the unsolved challenge of hydrating cyanohydrins. Herein, we report the design of new "donor-acceptor"-type platinum catalysts by precisely arranging electron-rich and electron-deficient ligands trans to one other, thereby enhancing both the nucleophilicity of the hydroxyl group and the electrophilicity of the nitrile group. Leveraging a high-throughput, automated workflow and evaluating a library of bidentate ligands, we have discovered that commercially available, inexpensive DPPF [1,1'-ferrocenendiyl-bis(diphenylphosphine)] provides superior reactivity. The corresponding "donor-acceptor"-type catalyst 2a is readily prepared from (DPPF)PtCl 2 , PMe 2 OH and AgOTf. The enhanced activity of 2a permits the hydration of a wide range of nitriles and cyanohydrins to proceed at 40 °C with excellent turnover numbers. Rational reevaluation of the ligand structure has led to the discovery of modified catalyst 2c, harboring the more electron-rich 1,1'-bis[bis(5methyl-2-furanyl) phosphino] ferrocene ligand, which demonstrates the highest activity towards hydration of nitriles and cyanohydrins at room temperature. Finally, the correlation between the electron-donating ability of the phosphine ligands with catalyst efficiencies of 2a, 2c, 2d and 2e in the hydration of nitrile 7 are examined, and the results support the "donor-acceptor" hypothesis.

Hydration of nitriles using a metal–ligand cooperative ruthenium pincer catalyst

“…There has been signicant recent interest in the development of nitrile hydration catalysts based on transition metals, but most systems reported to date still require relatively high temperatures to reach appreciable catalytic turnover. 7 Recent progress with Rh(I), 8 Ru(II), 9 Pd(II), 10 and Pt(II) 11 catalysts has allowed catalytic nitrile hydration under mild conditions, but additives are oen required for high activity (e.g., AgOTf in Grubbs' Pt(II)/phosphinous acid catalysts, 11 or Sc(OTf) 3 in Yin's Pd(II) catalysts 10 ).…”

Aqueous‐Phase Nitrile Hydration Catalyzed by an In Situ Generated Air‐Stable Ruthenium Catalyst

“…With complex RuCl 2 (PTA) 4 ,t he studies were conducted in ap H6.8 buffer and compared to the previously reportedd ata in water (Table 7). [46] Our group have reported that [(h 6 -arene)RuCl(k 2 -PTA-CPh 2 NHPh)]Cl can reach TOF of 285 h À1 at 100 8Cf or the hydration of benzonitrile;h owever, significant catalyst decomposition was observed under our reactions conditions. The RuCl 2 (PTA) 4 catalyst reacts faster than the in situ generated catalyst in both solvents ystems.…”

“…[45] Theh ydration of acetonitrile in tetrahydrofuran/water was reportedt oh ave aT OF of 318 h À1 at 40 8C( turnover number (TON) = 12 712) using [(DPPF)PtCl(PMe 2 OH)]OTf as the catalyst. [46] Our group have reported that [(h 6 -arene)RuCl(k 2 -PTA-CPh 2 NHPh)]Cl can reach TOF of 285 h À1 at 100 8Cf or the hydration of benzonitrile;h owever, significant catalyst decomposition was observed under our reactions conditions. [31] Other systemss uch as [(h 6 -arene)R-uCl 2 P(NMe 2 ) 3 ]h ave shown impressive reactivity and are synthe- sized from commercially available materials with TOF up to 11 400 h À1 using microwave( MW) irradiation (150 8C).…”

“…[1,46] Tyler and co-workers conducted a potassium cyanide (KCN) poisonings tudyw ith av ariety of nitrile hydration catalysts. [1,46] Tyler and co-workers conducted a potassium cyanide (KCN) poisonings tudyw ith av ariety of nitrile hydration catalysts.…”

“…Nitrile hydration catalysts often show ar eduction in activity in the presence of cyanide, ap articular problem with the hydration of cyanohydrins. [1,46] Tyler and co-workers conducted a potassium cyanide (KCN) poisonings tudyw ith av ariety of nitrile hydration catalysts. [15,21] In the case of acetonitrile hydration catalyzedb y[ ( h 6 -p-cymene)RuCl 2 (P(NMe 2 ) 3 )],t he reaction rate increased when 1equivalent of CN À was added and decreasedw ith increasing [CN À ].…”