Asymmetric Synthesis of C1-Chiral THIQs with Imines in Isoquinoline Rings

Abstract

Tetrahydroisoquinoline (THIQ) scaffolds are important structural units that widely exist in a variety of natural alkaloids and synthetic analogues. Asymmetric synthesis of C1-chiral THIQ is of particular importance due to its significant pharmaceutical, agrochemical, and other biological activities, and the usually distinct bioactivities exhibited by the two enantiomers. In this review, we highlight the significant advances achieved in this field, present recent asymmetric synthesis with imines in isoquinoline rings ordered according to the sequence of various substrate types. New strategies could be inspired and more types of substrates need further development.1 Introduction2 Catalytic Asymmetric Reaction of Dihydroisoquinolines2.1 Asymmetric Reactions of 3,4-Dihydroisoquinolines2.2 Asymmetric Reactions of Dihydroisoquinolinium Salts2.3 Asymmetric Reactions of C,N-Cyclic N′-Acyl Azomethine Imines2.3.1 NED [3+2] Cycloaddition of C,N-Cyclic N′-Acyl Azomethine Imines2.3.2 IED [3+2] Cycloaddition of C,N-Cyclic N′-Acyl Azomethine Imines2.3.3 [3+3] Cycloaddition of C,N-Cyclic N′-Acyl Azomethine Imines2.3.4 [4+3] Cycloaddition of C,N-Cyclic N′-Acyl Azomethine Imines2.3.5 Asymmetric Addition Reactions to C,N-Cyclic N′-Acyl Azomethine Imines2.4 Asymmetric Reactions of C,N-Cyclic Nitrones3 Catalytic Asymmetric Mannich Reactions of Isoquinolines4 Conclusions and Perspectives

Stereoselective synthesis of fused-, spiro- and bridged heterocycles via cyclization of isoquinolinium salts: a recent update

“…15 A recent review by Li, Chen and Gao focuses mainly on the synthesis of C 1 -chiral THIQs with imines in isoquinoline rings. 16 However, the past decade has witnessed great advances in the synthesis of annulated isoquinoline frameworks exploiting isoquinolinium ylides. There has been a marked growth in the number of new synthetic strategies involving bench-stable or in situ generated isoquinolinium salts; thus a new direction on this topic seems appropriate.…”

Iron Trichloride-Mediated Cascade Reaction of Aminosugar Derivatives for the Synthesis of Fused Tetrahydroisoquinoline–Tetrahydrofuran Systems

“…Furthermore, as optical enantiomers exert diverse biological activities, the asymmetric synthesis of THIQs has garnered a lot of attention in the scientific community. These strategies include the preparation of C-1-chiral THIQs by catalytic stereoselective processes or by using imines in isoquinoline rings . Moreover, simple approaches to access 3-substituted THIQ by iron-catalyzed tandem alcohol substitution and hydroamination using a sulfonamide nucleophile have been reported …”

“…These strategies include the preparation of C-1-chiral THIQs by catalytic stereoselective processes 11 or by using imines in isoquinoline rings. 12 Moreover, simple approaches to access 3-substituted THIQ by iron-catalyzed tandem alcohol substitution and hydroamination using a sulfonamide nucleophile have been reported. 13 …”

Asymmetric Synthesis of Tetrahydroisoquinoline Derivatives through 1,3-Dipolar Cycloaddition of C,N-Cyclic Azomethine Imines with Allyl Alkyl Ketones

“…A variety of isoquinoline alkaloids [ 1 , 2 , 3 ] exist in many natural products and drugs, and have a broad range of clinical applications, exhibiting a broad range of biological activities such as antitumor, anti-HIV, antibiotic, antifungal, antivirus, anti-inflammatory, anticoagulation, and bronchodilation, and can also act on the central nervous system [ 4 , 5 , 6 , 7 , 8 ]. In particular, it is tremendously noteworthy that all the above-illustrated bioactive tetrahydroisoquinolines have a chiral stereocenter at the C1-position [ 9 , 10 , 11 , 12 ]. Such representative examples include ( S )-salsolidine [ 13 ], ( S )-carnegine [ 14 ], ( S )-xylopinine [ 15 ] (in Figure 1 ), and so on.…”