Introduction of chirality at C1 position of 1-substituted-3,4-dihydroisoquinoline by its enantioselective reduction: synthesis of chiral 1-substituted-1,2,3,4-tetrahydroisoquinoline - a review

Abstract

There is a wide range of biological activities associated with C1 chiral carbon containing 1-substituted-1,2,3,4-tetrahydroisoquinolines (1-substituted-THIQs) which constitute the isoquinoline alkaloids, a large group of natural products. This work summarizes several novel catalytic stereoselective approaches to enantioselectively reduce the 1-substituted-3,4-dihydroisoquinolines (1-substituted-DHIQs) to produce the desired 1-substituted-THIQs. The 1-substituted-DHIQs were prepared by using the Bischler-Napieralski reaction. The enantioselective reduction of 1-substituted-DHIQs was accomplished by using chiral hydride reducing agents, by hydrogenation with a chiral catalyst, by enantioselective reduction of DHIQs possessing a chiral auxiliary at the imine nitrogen by achiral metallic hydride reducing agents, or by enzymatic catalysis. Among these methods, much more work was carried out on the hydrogenation of 1-substituted-DHIQs in the presence of a chiral catalyst. This review summarizes articles and advancements on this topic from 1972 to 2023.

Fig. 1. Structures of compounds having 1-substituted-THIQs.

Fig. 2. Generation of complex isoquinoline alkaloids from 1-substituted-THIQs.

Scheme 1. Bischler–Napieralski cyclization.

Scheme 2. Screening of chiral sodium triacyloxyborohydrides.

Scheme 3. Reduction into (S)-salsolidine, (S)-norcryptostyline I, and (S)-norcryptostyline II.

Scheme 4. Asymmetric chemical reduction of 1-benzyl-DHIQs.

Fig. 3. Chiral hydride reducing agents for the reduction of 1-benzyl-DHIQs.

Fig. 4. K-glucoride, Itsuno's reagent, and Mosher's reagent to get 1-substituted-6,7-dimethoxy-THIQs.

Scheme 5. Reduction using K-glucoride, Itsuno's reagent, Mosher's reagent.

Scheme 6. Reduction into (1R,3R)-6,8-dimethoxy-1,3-dimethyl-THIQ.

Fig. 5. Michellamine A and its two analogs.

Scheme 7. Synthesis of O,O-dimethylkorupensamine A.

Scheme 8. Asymmetric reduction of 1-substituted-6,7-dimethoxy-DHIQs with sodium N,N-phthaloylamino acyloxy borohydrides.

Fig. 6. (2S,4S)-BCPM, (4R,5R)-MOD-DIOP and the co-catalysts.

Scheme 9. Reduction into (S)-salsolidine and (S)-1-ethyl-6,7-dimethoxy-THIQ.

Fig. 7. Ru(ii) catalysts for ATH of 1-substituted-DHIQs.

Scheme 10. ATH of 1-substituted-DHIQs.

Scheme 11. Synthesis of (S)-laudanosine, (S)-homolaudanosine, and (S)-cryptostyline II.

Fig. 8. [Ir(COD)Cl]₂, (S)-BINAP, (2S,4S)-BCPM, phthalimide, and 3,4,5,6-tetrafluorophthalimide.

Scheme 12. Reduction into (S)-norlaudanosine, (S)-tetrahydrohomopapaverine, and (R)-norcryptostyline II.

Fig. 9. Korupensamine D and it's precursor.

Scheme 13. Reduction of (3R)-6,8-dimethoxy-1,3-dimethyl-DHIQ.

Scheme 14. Synthesis of (S)-calycotomine.

Scheme 15. Reduction into 1-[3-(benzyloxy)propyl]-6,7-dimethoxy-THIQ.

Fig. 10. (1S,2S)-Cp*RhClTsDPEN and (1R,2R)-Cp*RhClTsDPEN.

Scheme 16. Reduction with (1S,2S)-Cp*RhClTsDPEN and (1R,2R)-Cp*RhClTsDPEN.

Scheme 17. Synthesis of 1-phenyl-THIQ.

Fig. 11. (R)-BINAP, (R)-T-BINAP, and the ruthenium-optically active phosphine complex.

Scheme 18. AH with ionic Cp*Rh(iii) catalyst.

Fig. 12. Catalysts for AH in aqueous media.

Scheme 19. Reduction with sodium formate (aq) solution and CTAB.

Fig. 13. Metal complexes of O,O′-disulfonated N-tosyl-1,2-diphenylethylene diamine.

Scheme 20. Reduction of 1-substituted-6,7-dimethoxy-DHIQs.

Scheme 21. Synthesis of 1-substituted-2-benzyl-6,7-dimethoxy-THIQs.

Scheme 22. Production of (S)-6,7-dimethoxy-1-[2-(4-trifluoromethylphenyl)ethyl]-THIQ.

Fig. 14. Ruthenium catalysts for ATH of 6,7-dimethoxy-1-[2-(4-trifluoromethyl-phenyl)ethyl]-DHIQ.

Fig. 15. Difluorphos ligand, sunphos ligands, and synphos ligands.

Scheme 23. Generation of (R)-1-aryl-THIQs.

Scheme 24. AH of 6,7-dimethoxy-1-[2-(4-trifluoromethyl-phenyl)ethyl]-DHIQ.

Fig. 16. Taniaphos ligand.

Fig. 17. BINAP and P-phos moieties.

Scheme 25. AH with [Ir(COD)Cl]₂ and (S)–P-phos.

Fig. 18. Various chiral spiro iridium phosphoramidite complexes.

Scheme 26. AH with chiral spiro iridium phosphoramidite complex.

Scheme 27. Synthesis of (S)-xylopinine.

Fig. 19. Almorexant and its intermediate.

Scheme 28. Synthesis of the almorexant intermediate.

Fig. 20. TsDPEN complexes.

Scheme 29. ATH with TsDPEN complexes.

Scheme 30. Synthesis of an AMPA receptor antagonist.

Scheme 31. AH of 1-alkyl-DHIQs.

Fig. 21. Chiral cationic Ru complexes.

Scheme 32. ATH in water with 1.1 : 1 molar ratio of HCOOH and NEt₃.

Scheme 33. ATH of 1-aryl-6,7-dimethoxy-DHIQs.

Scheme 34. Reduction using Ru(ii)-TsDPEN catalyst.

Scheme 35. ATH of 1-aryl-DHIQs.

Scheme 36. ATH of 1-aryl-5-methoxy-DHIQs, 1-aryl-6-methoxy-DHIQs, and 1-aryl-7-methoxy-DHIQs.

Scheme 37. Synthesis of (S)-norcryptostyline I, (S)-norcryptostyline II, and an AMPA receptor antagonist.

Fig. 22. P-Trifluoromethyl ligands.

Scheme 38. AH of DHIQ hydrochlorides with P-trifluoromethyl ligands and by Ir-catalyst.

Scheme 39. AH of DHIQ hydrochlorides with P-trifluoromethyl ligands and by Ir-catalyst.

Fig. 23. Noyori – Ikariya half – sandwich complexes and their analogs.

Scheme 40. AH of 1-alkyl-DHIQs.

Fig. 24. Cp*Rh(TsDPEN) and Cp*Ir(TsDPEN) complex.

Scheme 41. ATH of 1-aryl-DHIQs.

Scheme 42. ATH of 1-methyl-6,7-dimethoxy-DHIQ.

Scheme 43. AH of 1-phenyl-DHIQs with dual stereo-control.

Scheme 44. AH of 1-aryl-DHIQs with dual stereo-control.

Scheme 45. Synthesis of an AMPA receptor antagonist with dual stereo-control.

Fig. 25. Josiphos-type binaphane ligands.

Scheme 46. Screening AH of 1-phenyl-DHIQ with Josiphos-type binaphane ligands.

Scheme 47. AH of 1-aryl-DHIQ with Josiphos-type binaphane ligands.

Scheme 48. Reduction of 1-phenyl-DHIQ.

Fig. 26. Chiral catalysts for the reduction of 1-phenyl-DHIQ.

Fig. 27. Solifenacin and its intermediate.

Scheme 49. Reduction into solifenacin intermediate.

Scheme 50. Asymmetric synthesis of fumarizine.

Scheme 51. Asymmetric synthesis of (R)-noranicanine.

Scheme 52. Asymmetric synthesis of (S)- and (R)-salsolidines and (R)-cryptostyline.

Scheme 53. Asymmetric synthesis of (S)- and (R)-salsolidines.

Scheme 54. Asymmetric synthesis of (R)-cryptostyline.

Scheme 55. Enantioselective synthesis of (R)- and (S)-cryptostyline II.

Scheme 56. Asymmetric synthesis of dehassiline.

Scheme 57. Enantioselective synthesis of (S)-1-benzyl-2-propyl-6,7-dihydroxy-THIQ.

Scheme 58. Enantioselective reduction by AoIRED.

Scheme 59. Enantioselective reduction by SnIRED.

Scheme 60. Enantioselective reduction by hindrance-tolerated IREDs.

Scheme 61. Enantioselective reduction by IRED2 or IRED45.

Scheme 62. Enantioselective reduction by D-type and Y-type IREDs.

Scheme 63. Enantioselective reduction by IRED45 and its mutant.

Scheme 64. Enantioselective reduction by D187 subgroup of IREDs.

Md. Moaz Ahmed Asif

Susmita Roy Lisa

Nazmul Qais