Rh-Catalyzed Enantioselective Allylation of N-Tosyl- and N-Nosylaldimines: Total Synthesis of (−)-Crispine A

Abstract

The unprecedented development of asymmetric Rh-catalyzed 1,2-allylation of N-Ts- and N-Ns-aldimines is achieved. This protocol utilizes potassium allyltrifluoroborates and various aldimines to generate enantioenriched homoallylic amines in the presence of 3.0 mol % of Rh(I)/L1b catalyst with up to 90% yield, 98% ee (R = H), and 10:1 diastereoselectivity (R = Me or Ph), yielding the same major diastereomer when using potassium (E)- and (Z)-crotyltrifluoroborate. Its synthetic utility is also illustrated in the total synthesis of (-)-crispine A.

Enantioselective Rhodium-Catalyzed Allylation of Aliphatic Imines: Synthesis of Chiral C-Aliphatic Homoallylic Amines

“…While these approaches are known to produce enantioenriched 1-aryl and 1-alkenyl alkylamines, similar allylation reactions to afford the corresponding homoallylic amines , remain unexplored. , Hence, developing the enantioselective allylation of aliphatic aldimines would be highly desirable to address this deficiency. We report herein on the first asymmetric allylation of aliphatic aldimines in the presence of rhodium/chiral bicyclo[2.2.1]­heptadiene catalysts , to afford optically active C-aliphatic homoallylic amines and its use in the total syntheses of natural indolizidine and piperidine alkaloids.…”

“…We first examined the asymmetric addition of potassium allyltrifluoroborate ( 2a ) with the Ts-protected aldimine 1a in the presence of 3 mol % of a catalyst generated in situ from [RhCl­(C 2 H 4 ) 2 ] 2 and the chiral diene ligand L1 (Table ). The desired adduct 3aa was obtained in 18% yield with 88% ee in dioxane at 60 °C when no H 2 O was added (entry 1), with the formation of the α,β-unsaturated imine 4a , derived from the self-condensation of 1a , and 4a -degradation accounting for the low product yield. While adding molecular sieves failed to improve the yield (entry 2), adding H 2 O mitigated the formation of 4a , with 3aa being produced in up to 96% yield and 93% ee (entries 3 and 4).…”

Synthesis of Pyrrolo[2,1‐a]isoquinoline Class of Natural Product Crispine A

“…Wu et al reported an asymmetric Rh-catalyzed 1-2 allylation of N-tosylimines 139 for the enantiopure synthesis of (À )-crispine A (À )-1 in 2018 (Scheme 34). [63] Asymmetric allylation of N-tosylimine 139 was achieved in the presence of rhodium catalyst and chiral bicyclo[2.2.1]heptadiene ligand 141 with allyltrifluoroborate 140 as the nucleophile. Subsequently, nitrogen was protected as its Boc derivative and the tosyl group was removed to afford the intermediate 144.…”

Application of Rh(I)/Bicyclo[2.2.1]heptadiene Catalysts to the Enantioselective Synthesis of Chiral Amines

“…The employment of a rhodium catalyst in situ generated from [RhCl(C 2 H 4 ) 2 ] 2 and the chiral diene ligand L1i permitted the potassium allyltrifluoroborate 21 to be added, as a pre‐nucleophile, to N ‐Ts arylaldimines 4 and N ‐Ns arylaldimines 7 to smoothly produce the corresponding chiral homoallylic amines 22 and 23 in 41–90 % yields and 83–98 % ees (Table 5). [23] …”