Asymmetric Hydrogenation of Isoxazolium Triflates with a Chiral Iridium Catalyst

Abstract

The iridium catalyst [IrCl(cod)]2 -phosphine-I2 (cod=1,5-cyclooctadiene) selectively reduced isoxazolium triflates to isoxazolines or isoxazolidines in the presence of H2 . The iridium-catalyzed hydrogenation proceeded in high-to-good enantioselectivity when an optically active phosphine-oxazoline ligand was used. The 3-substituted 5-arylisoxazolium salts were transformed into 4-isoxazolines with up to 95:5 enantiomeric ratio (e.r.). Chiral cis-isoxazolidines were obtained in up to 89:11 e.r., with no formation of their trans isomers, when the substrates had a primary alkyl substituent at the 5-position. The mechanistic studies indicate that the hydridoiridium(III) species prefers to deliver its hydride to the C5 atom of the isoxazole ring. The hydride attack leads to the formation of the chiral isoxazolidine via a 3-isoxazoline intermediate. Meanwhile, in the selective formation of 4-isoxazolines, hydride attack at the C5 atom may be obstructed by steric hindrance from the 5-aryl substituent.

Isoxazolidine: A Privileged Scaffold for Organic and Medicinal Chemistry

“…Hydrogenation of isoxazolinium salts 117 in the presence of iridium catalyst lead to a fully saturated cis-isoxazolidine 118 in excellent yield and er (up to 89:11), Scheme 38. 171 Interestingly, when the reaction was performed in the presence of a double amount of catalysts in THF at 70 °C for 4 h, a mixture of saturated and unsaturated rings 120, 121, and 122 was obtained, Scheme 39.…”

Enantioselective Catalytic Asymmetric A3 Coupling with Phosphino-Imidazoline Ligands

“…In order to determine the relative importance of different chiral elements of ( S , S , R a )-UCD-PHIM ( 1a ) in A3 coupling, the closely related ligands 1b–1d were prepared and tested (Scheme ). − …”

“…Next, we prepared ligand 1c , ( S , S )-Diph-PHOX, in which the imidazoline unit of ligand 1b was replaced by an oxazoline unit . The copper complex of 1c furnished product 5d in a reduced yield of 32% and ee of 42%.…”

Further Developments and Applications of Oxazoline-Containing Ligands in Asymmetric Catalysis

“…Kuwano developed an Ir-catalyzed enantioselective hydrogenation of isoxazolium triflates (181 and 183) to furnish enantioenriched 4-isoxazolines (182) or isoxazolidines (184) (Scheme 50). 65 The hydrogenation of 5-arylisoxazolium triflates (181) exclusively provided the corresponding 4isoxazolines (182) with good enantioselectivities (up to 90% ee) whereas 5-alkylated isoxazolium triflates (183) selectively furnished cis-3,5-disubstituted isoxazolidines (184) with ees up to 78%. The enantioselectivity was strongly affected by the hindrance from the 5-substituent on the isoxazole ring.…”