Iridium-Catalyzed Asymmetric Hydrogenation of Sterically Hindered Cyclic Imines for Enantioselective Synthesis of Tetrahydroisoquinolines

Abstract

An efficient enantioselective hydrogenation of sterically hindered cyclic imines catalyzed by the Ir- t Bu-ax-Josiphos complex has been described, producing a series of useful chiral bulky tetrahydroisoquinoline analogs in high isolated yields (85–96%) with good to excellent enantioselectivities (74–99% ee). This transformation provided highly straightforward access to the useful derivatives of tetrahydroisoquinolines, which are of great potential value in drug molecule and natural product research.

Chiral 8-Amino-5,6,7,8-tetrahydroquinoline Derivatives in Metal Catalysts for the Asymmetric Transfer Hydrogenation of 1-Aryl Substituted-3,4-dihydroisoquinolines as Alkaloids Precursors

“…Moreover, the aqueous media usually employed in the ATH protocol generally avoid the use of the most performing but moisture sensitive diphosphine ligands, refs. [ 15 , 16 , 17 , 18 , 19 ] thus evoking the need for new catalysts able to broaden the scope toward the most challenging dihydroisoquinolines (DHIQs). The related reduction products, namely tetrahydroisoquinolines (THIQs), indeed account for an important class of alkaloids and semi-synthetic derivatives endowed with multiple relevant biological properties ( Figure 1 ) [ 20 , 21 , 22 , 23 , 24 ].…”

Highly Enantioselective Ir-Catalyzed Hydrogenation of Pyrazolo[1,5-a]pyrimidine for the Synthesis of Zanubrutinib

“…Although we tried to obtain a single crystal sample, multiple attempts failed because of the foam attribute of the reduction product. 11 Therefore, we had to change our strategy. Based on our previous experience, when nitrogen was connected to a Ts group, the obtained benzenesulfonamide possessed fine crystallinity.…”

Recent Advances in the Enantioselective Synthesis of Chiral Amines via Transition Metal-Catalyzed Asymmetric Hydrogenation

“…In 2020, the same catalytic system was applied to the AH of sterically hindered cyclic imines P30d , achieved with good to excellent enantioselectivities (74–99% ee) (Scheme ). This novel family of chiral ligands was also applied to the iridium-catalyzed AH of acyclic N -aryl imines …”

“…In 2020, the same catalytic system was applied to the AH of sterically hindered cyclic imines P30d, achieved with good to excellent enantioselectivities (74−99% ee) (Scheme 20). 158 This novel family of chiral ligands was also applied to the iridium-catalyzed AH of acyclic N-aryl imines. 159 In 2013, Zanotti-Gerosa's group (Johnson-Matthey) described a novel approach to the synthesis of the urinary antispasmodic drug solifenacin (Scheme 21).…”