New biphenol-based, fine-tunable monodentate phosphoramidite ligands for catalytic asymmetric transformations

Abstract

Monodentate phosphoramidite ligands have been developed based on enantiopure 6,6-dimethylbiphenols with axial chirality. These chiral ligands are easy to prepare and flexible for modifications. The fine-tuning capability of these ligands plays a significant role in achieving high enantioselectivity in the asymmetric hydroformylation of allyl cyanide and the conjugate addition of diethylzinc to cycloalkenones. R ecently, chiral monodentate phosphorus ligands (phosphites, phosphoramidites, and phosphonites) have been attracting considerable interest for their use in catalytic asymmetric synthesis, because the chiral catalysts bearing these ligands have proven to be highly efficient in various asymmetric reactions. This is a previously univestigated wave in the design of chiral ligands, which makes a sharp contrast to almost three decades of predominance by C2 symmetrical bidentate phosphorus ligands for a variety of catalytic asymmetric transformations. This wave of designing simple and readily modifiable chiral structures, which are easy to synthesize, is fitting very well to the trendy and highly practical combinatorial approaches to the development of the most suitable chiral ligand for a particular catalytic asymmetric process of commercial value or academic interest. This approach is currently considered most practical rather than trying to develop a universal and almighty chiral ligand for different types of catalytic asymmetric transformations.Before the launch of our research program on the development of chiral monodentate phosphorus ligands based on enantiopure 2,2Ј-dihydroxy-6,6Ј-dimethylbiphenyls, by far, the most studied monodentate ligands were phosphites and phosphoramidites based on TADDOL (1) (1) BINOL (2) (2-4), a spirobiindanediol (3) (5), or an achiral biphenol (4) (6, 7) bearing a chiral or achiral secondary alcohol or amine (Fig. 1). These ligands have found a wide range of applications in metalcatalyzed asymmetric transformations such as hydrogenation (5, 8-10), 1,4-additions of dialkylzinc (11, 12) and boronic acids (13) to enones, hydrovinylation (14), hydrosilylation (15), intramolecular Heck reaction (16), hydroformylation (17), allylic alkylation (18, 19), amination (20), and etherification (21).We have been developing a previously uninvestigated class of chiral monodentate phosphite and phosphoramidite ligands, 5 and 6, from readily accessible enantiopure, axially chiral biphenyls ( Fig. 2) and have recently published the successful application of chiral monophosphite ligands 5 to the Rh(I)-catalyzed asymmetric hydrogenation of dimethyl itaconate (Fig. 2) (22).One of the salient and practical features of these chiral monophosphite ligands is the fine-tuning capability with modifiable substituents R 1 , R 2 , and R 3 in the formula 5. This fine-tuning capability of ligands 5 (phosphites) and 6 (phosphoramidites) is expected to play a crucial role in the application of these ligands to a variety of catalytic asymmetric reactions. In fact, we have demonstrated that the substituents (R 2 )...

Composition of catalyst resting states of hydroformylation catalysts derived from bulky mono-phosphorus ligands, rhodium dicarbonyl acetylacetonate and syngas

“…These are often independent of catalyst concentration. As previously discussed, it is common for many mono-phosphorus ligands to form quite C. In the previous work by Ojima and co-workers [7], the enantiomerically pure form of ligand 2 gave poorer regioselectivity and no enantioselectivity in hydroformylation. It therefore seems very likely that this bulky ligand does not coordinate to rhodium under hydroformylation conditions, and that the higher branched selectivity observed for propene hydroformylation with ligand 2 relative to ligand 1 ( Table 1), is almost certainly due to the unmodified catalyst.…”

“…Ojima and co-workers [7] reported the use of enantiopure mono-dentate phosphoramidites in the enantioselective hydroformylation of allyl cyanide. Allyl cyanide does tend to give preference for the branched aldehyde [7,8] but the regioselectivity reported for ligand 1 is unusually high (B:L 96:4).…”

“…Allyl cyanide does tend to give preference for the branched aldehyde [7,8] but the regioselectivity reported for ligand 1 is unusually high (B:L 96:4). Related ligand 2 gave no enantioselectivity and reduced regioselectivity.…”

Asymmetric Hydroformylation

“…When vinyl acetate was the substrate, very poor ees were obtained (Scheme 13) [49,50]. However, in 2004, Ojima and co-workers reported the use of the phosphoramidite ligand 55 (Scheme 13), related to monophosphite 54, in the Rh-catalyzed asymmetric hydroformylation of allyl cyanide and achieved excellent regioselectivities together with the highest enantiomeric excess (80%) ever reported for this reaction with a monodentate ligand [86]. These results, although still far from those obtained with bidentate ligands, clearly indicated that achieving high ees using monodentate ligands is possible.…”

“…Therefore, the presence of a single coordination isomer, in this case with ligand coordinated in an 86 B.F. Perandones et al…”