Synthesis of Enantioenriched 5,6‐Dihydrophenanthridine Derivatives through retro‐Carbopalladation of Chiral o‐Bromobenzylamines

Abstract

Retro‐carbopalladation of aldimines in the presence of a suitable β‐hydrogen atom has been observed in the Pd‐catalyzed homocoupling reactions of o‐bromobenzylamines, providing an expeditious synthetic route to 5,6‐dihydrophenanthridine derivatives. Furthermore, a highly enantioselective synthesis of 6‐aryl‐substituted 5,6‐dihydrophenanthridines was achieved in a one‐pot manner by taking advantage of Rh and Pd catalysis.

Recent Developments in Enantioselective Multicatalyzed Tandem Reactions

“…In 2015, Lautens et al. reported an example of bimetallic rhodium/palladium sequential catalysis to promote enantioselective tandem arylation/homocoupling reactions of ortho ‐bromobenzaldimines 132 with arylboroxines 133 . The process depicted in Scheme was sequentially catalyzed by 2.5 or 5 mol% of a rhodium complex derived from chiral diene ligand 134 , and 3 or 5 mol% of Pd(PPh 3 ) 4 .…”

“…A possible mechanism for the precedent reaction is depicted in Scheme . First, oxidative addition of ortho ‐bromobenzylamine BP to Pd(0) generated intermediate BQ which was further deprotonated to give palladacycle BR .…”

“…In 2015, Lautens et al reported an example of bimetallic rhodium/palladium sequential catalysist op romote enantioselective tandem arylation/homocoupling reactions of ortho-bromobenzaldimines 132 with arylboroxines 133. [59] Thep rocess depictedi nS cheme 42 was sequentially catalyzed by 2.5 or 5mol% of ar hodium complexd erived from chiral dienel igand 134, and 3o r5mol%o fP d(PPh 3 ) 4 .T he chiral rhodium catalyst promoted at 60 8 8Ci nt oluene as solvent the asymmetric arylation of ortho-bromobenzaldimines 132 with arylboroxines 133 as nucleophiles to afford intermediates BO which subsequently underwent at 120 or 130 8 8Ca fter addition of the palladium catalyst ahomocoupling to yield the final biologically interesting chiral 6-aryl-substituted 5,6-dihydrophenanthridine derivatives 135 in moderate to high yields (48-78%) and uniformlye xcellent enantioselectivities (98 Scheme 37. Magnesium-/organocatalyzed dominoi ntramolecular 1,5-hydride transfer/cyclization reaction of oxindole derivatives.…”

“…Ap ossible mechanism for the precedentr eactioni s depicted in Scheme 43. [59] First, oxidative addition of ortho-bromobenzylamine BP to Pd( 0 matic aldehydes 136,a romatic amines 66 and CO 2 . [60] Thef irst step of the process involved at 25 8 8Ci nD CE as solvent ac hiral copper catalyst in situ generated from 10 mol% of Cu(OTf) 2 and 12 mol% of chiral Pybox ligand 137 that promoted the coupling between alkyne 53,a romatic aldehyde 122 and aromatic amine 66 to provide the corresponding chiral amine intermediate BY.T hen, addition of 20 mol%o fA gOBz and CO 2 under pressure in the presence of 1,3-diphenylguanidine (DPG) as ab ase in DCEa ss olvent induced at 25 8 8Ct he second step of the sequence,d ealing with the carboxylative cyclization of intermediate BY into finalp roduct 138.T his sequential bimetallic relay catalysisa llowed ar ange of chiral N-aryl 2-oxazolidinones 138 to be synthesized in bothu niformly high yields (82-99%) and enantioselectivities( 90-96% ee), as illustrated in Scheme44.…”