Reversible nucleophilic addition can lower the observed enantioselectivity in palladium-catalyzed allylic amination reactions with a variety of chiral ligands

Proofreading Experimentally Assigned Stereochemistry Through Q2MM Predictions in Pd-Catalyzed Allylic Aminations

“…L6 has previously been used by another group with similar reaction conditions, but using benzylamine rather than indoline as the nucleophile. 20 In that case, the absolute con guration predicted by the force eld matches the absolute con guration described in the literature. To study this, the stereochemistry assignment was reexplored experimentally (see Supporting Information).…”

“…A validation dataset containing 77 structures (Figs. S3 and S4, Table S3 in Supporting Information) assembled from the literature 18,20,[37][38][39][40][41][42][43][44] was used to test the performance of the TSFF for systems different than the training set (Figure 2A). 1,3-Diphenyl propenyl was used as the allyl component reacting with 16 different amines, catalyzed by the Pd-complexes of 53 different P,N ligands.…”

“…Some common ligands used for this reaction include the PHOX ligands, phosphite-oxazoline ligands, and aminoalkyl-phosphine ligands. 6,[17][18][19][20][21] These ligands can control exo-endo preference through the chiral oxazoline/amine moiety which, thanks to the trans phosphorus, is in close proximity to the reacting allyl terminus (Figure 1C). 16 There have been a few methods developed to predict stereoselectivity in asymmetric catalysis.…”

Proofreading Experimentally Assigned Stereochemistry Through Q2MM Predictions in Pd-Catalyzed Allylic Aminations

“…L6 has previously been used by another group with similar reaction conditions, but using benzylamine rather than indoline as the nucleophile. 20 In that case, the absolute configuration predicted by the force field matches the absolute configuration described in the literature. To study this, the stereochemistry assignment was reexplored experimentally (see Supporting Information).…”

“…For cases with more than two competing transition states, the ratio is obtained by a Boltzmann summation over diastereomeric pathways. S3 in Supporting Information) assembled from the literature 18,20,[35][36][37][38][39][40][41][42] was used to test the performance of the TSFF for systems different than the training set (Figure 2A). 1,3-Diphenyl propenyl was used as the allyl component reacting with 16 different amines, catalyzed by the Pd-complexes of 53 different P,N ligands.…”