On the Use of Phosphoramidite Ligands in Copper-Catalyzed Asymmetric Transformations with Trialkylaluminum Reagents

Abstract

[reaction: see text] Phosphoramidites based on BINOL readily react with trimethylaluminum in "noncoordinating" solvents, leading to the corresponding aminophosphine which is the real ligand in copper-catalyzed asymmetric transformations. This artifact explains the experimental differences in the asymmetric ring opening of meso bicyclic hydrazines using dialkylzinc or trialkylaluminum reagents as nucleophiles.

Practical Synthesis of SimplePhos Ligands: Further Development of Alkyl‐Substituted Phosphanamines

“…In 2006, chiral monodentate phosphanamine ligands were prepared for the first time rather by accident than intentionally. Alexakis and Micouin observed that phosphoramidite ligands such as L1 when exposed to Me 3 Al in noncoordinating solvents like toluene or CH 2 Cl 2 exchanged the diol moiety for methyl substituents affording the corresponding phosphanamine L2 (Scheme ) 1. This reaction does not occur in the presence of strongly coordinating solvents such as THF or with less oxophilic organozinc reagents.…”

“…Hence aryl‐substituted SimplePhos ligands can be conveniently handled without the use of a glovebox or other precautions and were used in a manifold of asymmetric transformations (Scheme ). For example, aryl‐substituted ligands were found to be efficient ligands for the Cu‐catalyzed ring‐opening of polycyclic meso ‐hydrazines1–3 and oxabenzonorbornadienes,4 the kinetic resolution of cyclic vinyloxiranes,5 the Cu‐catalyzed asymmetric conjugate addition with diorganozinc,2,6 triorganoaluminium,2,7 and Grignard reagents8 as well as for Cu‐catalyzed allylic alkylations 3,6. Moreover, aryl‐substituted SimplePhos ligands have been used for Rh‐catalyzed asymmetric hydroformylation reactions 9.…”

Asymmetric Pentafulvene Carbometalation—Access to Enantiopure Titanocene Dichlorides of Biological Relevance

“…Additionally, we discovered that MTBE was the optimal solvent and highly purified phosphoramidite L1 is required as while its degradation product L2 engenders significant ligand acceleration [6] it does so with minimal enantioselectivity (Run 8). While AlR3 reagents are known to cleave phosphoramidites in low polarity solvents [7] this is not normally an issue with ZnR2 reagents and we could detect no L1 degradation at the end of 16 h runs. [a] Cu-source and L* in solvent (2.0 mL) stirred for 1 h followed by 1e (0.5 mmol).…”

Copper‐Catalyzed Asymmetric Allylic Alkylation

“…This last observation was soon after explained by Micouin and Alexakis, who discovered that in non-coordinating solvents, such as toluene or dichloromethane, an aluminum reagent generates phosphinamines (RR)-L25 by in situ reaction with the chiral phosphoramidite ligands (S,RR)-L4 or (R,RR)-L6 (Scheme 48). [61] Shortly after, the ring-opening of meso polycyclic hydrazines 124 and 125 was improved with the use of a novel class of monodentate phosphorus ligands described by Alexakis and co-workers. [62] A new generation of phosphinamine ligands L26,L27, termed SimplePhos, untouched by the aluminum reagent, would enable higher enantioselectivities than previously reported with ee values up to 94 % (Scheme 49).…”