60th Annual Report on Research 2015

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Reports: ND352709-ND3: New Homoleptic Rare-Earth Metal Complexes for Catalytic Hydrophosphination

Progress Report – Year 2   Overview. The goal of this research project is the development of new lanthanide complexes with exceptional activity for the catalytic hydrophosphination of a wide range of unsaturated substrates. In our previous work, homoleptic rare-earth metal complexes supported by alpha-metalated dimethylbenzylamine ligands were shown to be effective as precatalysts for the hydrophosphination of heterocumulenes such as carbodiimides, isocyanates, and isothiocyanates. Over the past year, our efforts have targeted expansion of the substrate scope amenable to catalytic hydrophosphination with these catalysts, while we have also investigated the related hydrophosphinylation chemistry, in which a secondary phosphine oxide (R₂P(O)H) is added to an unsaturated framework similar to the R₂PH units added in hydrophosphination. Specific substrates that can been utilized in this catalysis now include imines, alpha,beta-unsaturated ketones, 1,3-dienes, and allenes. Additionally, we have recently found an efficient method to add two equivalents of secondary phosphine oxides to nitriles, yielding the corresponding amine products.   Synthesis. The homoleptic alpha-metalated N,N-dimethylbenzylamine precatalyst, (DMBA)₃La, was synthesized following a simple procedure involving salt metathesis of lanthanum chloride with alpha-potassiated dimethylbenzylamine at -50 °C in THF (Scheme 1). The product was isolated by recrystallization from THF/pentane at -25 °C in excellent yield.       Scheme 1. Synthesis of alpha-La(DMBA)₃.     Catalytic Reactions: Unsaturated C=C Reagents. The lanthanum precatalyst was utilized in the hydrophosphination of moderately activated C=C moieties such as alpha,beta-unsaturated ketones, conjugated 1,3-dienes and allenes (Table 1). During the course of these studies, we discovered that phosphorus reagents such as diphenylphosphine oxide provided faster catalytic reactions and displayed a wider substrate scope, as evidenced by the differences in reactivity with cyclohexylallene (Table 1). A full substrate study has not yet been performed, but it seems clear that many activated C=C reagents are amenable to hydrophosphination reactions under lanthanide catalysis conditions.  

Table 1. Catalytic addition of phosphines to unsaturated C=C moieties.^a

 

Unsaturated C=C	Ph2PH yield (%)	Ph2P(O)H yield (%)
	86	90
	93	87
	90	82
	none	73b

^a Conditions: phosphine (1.15 mmol), alkene (1.00 mmol), catalyst (0.10 mmol), pyridine (3 mL). ^b Reaction stirred at 80°C.   Imines. Given the enhanced catalytic activity when using secondary phosphine oxides, we focused primarily on catalytic hydrophosphinylation with many of the new substrates. Simple imines proved to be readily hydrophosphinylated, giving excellent yields of the addition products with the formation of new P-C bonds in the process (Table 2). These species are interesting due to the new P-C-N framework that results in this addition process.  

Table 2. Catalytic addition of secondary phosphine oxides to imines.^a

 

 

R	yield (%)
H	92
Cl	95
MeO	89
Me2N	85
CF3	90

^a Conditions: phosphine oxide (1.15 mmol), imine (1.00 mmol), catalyst (0.10 mmol), pyridine (3 mL).   Nitriles. Our most recent experiments have targeted the addition of two equivalents of phosphine oxides to the C≡N bond of nitriles. The lanthanide catalysts have proven to be quite effective in this reaction, giving moderate yields of products resulting from the formation of two C-P bonds and full reduction of the nitrile to an amino (NH₂) group (Table 3). Aryl nitriles, such as benzonitrile, gave lower yields of the doubly hydrophosphinylated product. Instead they seem to undergo either a side reaction or a secondary reaction to give another species. Determination of this species remains an ongoing pursuit in our current research efforts.  

Table 3. Catalytic addition of secondary phosphine oxides to nitriles.^a

 

 

R	yield (%)
Me	85
Et	77
MeOCH2CH2	67
Me2NCH2CH2	70
Ph	35

^a Conditions: phosphine oxide (1.15 mmol), nitrile (1.00 mmol), catalyst (0.10 mmol), pyridine (3 mL).   Summary. The hydrophosphination and hydrophosphinylation chemistry supported by (DMBA)₃La catalysts has proven to be amenable to a wide range of unsaturated substrates, with successful addition reactions involving C=C, C=N, and C≡N moieties. Current efforts have focused on exploring the breadth of substrates amenable to these addition reactions. Future work will involve complete investigation of these new catalytic reactions, with the full scope of imines, allenes, and nitriles utilized to produce new phosphine containing products.   Human Resources Development. Many researchers have played a role in the chemistry accomplished through this PRF grant funding, including those research group members working on unrelated projects, as each of them has been involved in intellectual discussions, editing of manuscripts and posters, and refinement of presentations. The researchers most directly involved in this project include three graduate students (Andrew Behrle, PhD 2012, now a post-doctoral associate at the University of Missouri and Miriam Basiouny and Sreejit Menon, both PhDs in progress) and one undergraduate (Deborah Dollard, BS in progress).   Conclusions. The research supported by the PRF New Directions grant has led to a new field of chemistry in the Schmidt group. With hydrophosphination and hydrophosphinylation catalysis using lanthanide complexes, we have expanded beyond the palladium-based hydroamination chemistry that was previously the primary specialty of our research group. This Year Two Report summarizes our recent results in this field. It is clear that these catalysts are very effective at hydrophosphination and hydrophosphinylation of unsaturated substrates with our most recent experiments displaying excellent catalytic activity to form several unprecedented reaction products. These results will be published in the near future and summarized at the conclusion of this grant funding. Ultimately, these new reaction manifolds will form the foundation of future submissions for major federal grant funding.