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Reports: DNI352119-DNI3: Acylation of Arenes via Catalytic C-H Bond Functionalization and Aerobic Alcohol Oxidation

Marion H. Emmert, PhD, Worcester Polytechnic Institute

1. OVERVIEW

In order to create sustainable syntheses for arylketones [[1]], we have proposed to investigate a novel catalytic cycle (Scheme 1), consisting of (A) aerobic alcohol oxidations, (B) C-H activation, and (C) aldehyde carbometalation.

 

2. SCIENTIFIC REPORT

2.1 Ir catalyzed aerobic alcohol oxidations.

2.1.2. Non-innocence of Ag. Further investigations of aerobic alcohol oxidation suggested that the presence of Ag(I) lessens the catalytic performance. Possible mechanisms for this process are Ag promoted oxidations of the Cp*Ir catalysts [[2]] or the formation of dinuclear Ir species from Ir-H intermediates in the presence of Ag. [[3]]

 

2.1.3 Isolation of decomposition products. In order to better understand which catalyst decomposition products are formed during catalysis, we investigated the inorganic complexes after the reaction and observed a catalytically inactive, bimetallic Ir hydride species [Cp*IrCl(µ‑H)]2 (3) at ‑13.6 ppm and [(Cp*IrCl2)2(µ‑H)(µ‑Cl)] (4) (Scheme 2) [[4]].

 

 

 

This suggests that several different Ir-H species might be involved during the air oxidation of alcohols or may be formed as decomposition products. No Ir-H resonances were in the presence of Ag additives.

 

2.1.4 Effect of solvents and additives on catalyst stability. The effect of H2O and other additives was investigated, suggesting that the water content indeed contributes to catalyst stabilization (Schemes 4/5).

 


Scheme 4. Effect of Water in Different Solvents.

We speculated that the catalytic cycle would be accelerated by a proton buffer. Consequently, AcOH/NaOAc and CF3CO2H/NaO2CCF3 buffer systems were tested in various toluene/H2O mixtures. In all cases, the AcOH/NaOAc buffer provided higher 24 h yields of 2 up to 83%. Reactions were also performed at 0.1 mol % catalyst loading, affording 270 TONs [[5]]. This is to our knowledge the highest TON achieved to date for Ir catalyzed aerobic alcohol oxidations, which do not proceed through acceptor-less dehydrogenation mechanisms [[6]].


Scheme 5. 24 h Reactivity vs. water content without (left) and with buffer system (right).

 

2.1.5 Substrate scope study. A variety of secondary alcohols were readily transformed into the resulting ketones. Overall, benzylic secondary alcohols were reactive substrates with both electron-rich and electron-neutral substituents; secondary, non-benzylic alcohols were also good substrates.

2.2 Aldehyde carbometalations.

Efforts during 2013/14 focused then on optimizing the yields of aldehyde carbometalations for the stoichiometric reactions at Ir, since the respective yields for this reaction (Scheme 6) was determined to produce less than 0.5% of aryl ketone product.

We demonstrated that the proposed C-C bond formation proceeds under conditions analogous to the best aerobic oxidation conditions by reacting [Cp*IrCl2]2 with 2-phenyl pyridine in the presence of benzaldehyde and NaOAc/AcOH buffer (Scheme 6). Reactions between cyclometalated complex 5 and benzaldehyde under analogous conditions proceeded less readily (Scheme 6) and afforded only 2% of the acylation product 7.

 

 

2.3 C-H Activation.

2.3.1 C-H Activation under Aerobic Oxidation Conditions. We sought to demonstrate that C-H activation is possible under aerobic oxidation conditions (Scheme 7); formation of the cyclometalated complex 5 was observed.

 

 

2.3.2 Non-Directed C-H Activation with Oxidatively Stable Ligands and Additives.

We synthesized Cp*Ir(H2O)3(OTf)2 as a Ag-free catalyst precursor for H/D exchange; 11 TONs were obtained. Several ligands and basic additives (Scheme 8) further promoted the C-H activation reactivity (TONs >20). We conclude that ligands with moderate steric hindrance and strong electron-donating features are most promising for non-directed C-H activation.

 

 

 

3. IMPACT OF AWARD ON PI’S CAREER AND ON SUPPORTED STUDENTS

A publication on aerobic oxidation is currently under review. In addition, a current senior thesis student explores aerobic oxidations of biomass substrates. Another senior thesis student continues the work in the PIs laboratory on H/D exchange.

The work completed under this award has provided data for 3 poster presentations by the PI (2 at Gordon Research Conferences; 1 at WPI), 2 poster presentations by the postdoc, and 3 poster presentations by an undergraduate researcher in the group. The PI has spoken about the work conducted under this grant in 4 invited lectures. The results have been used to apply for NSF funding in 2013 and 2014.


[1] Bauer, K.; Garbe, D.; Surburg, H., Common fragrance and flavor materials. 4th Edition ed.; Wiley-VCH: Weinheim, 2001.

[2] Ringenberg, M. R.; Kokatam, S. L.; Heiden, Z. M.; Rauchfuss, T. B., J. Am. Chem. Soc. 2007, 130 (3), 788-789.

[3] a) Turlington, C. R.; Harrison, D. P.; White, P. S.; Brookhart, M.; Templeton, J. L., Inorg. Chem. 2013, 52 (19), 11351-11360; b) Feldman, J.; Calabrese, J. C., Inorg. Chem. 1994, 33 (25), 5955-5956; c) Bachechi, F., J. Organomet. Chem. 1994, 474 (1–2), 191-197; c) Einstein, F. W. B.; Jones, R. H.; Zhang, X.; Sutton, D., Can. J. Chem. 1989, 67 (11), 1832-1836; e) Sykes, A.; Mann, K. R., J. Am. Chem. Soc. 1988, 110 (24), 8252-8253.

[4] Feng, Y.; Jiang, B.; Boyle, P. A.; Ison, E. A., Organometallics 2010, 29 (13), 2857-2867.

[5] TONs were calculated in agreement with reference 14 based on the amount of [Cp*IrCl2]2 in the reaction.

[6] The so far highest TON in aerobic, non-dehydrogenative alcohol oxidations at Ir is 70 with [Cp*IrCl(bipyrimidine)]+ as catalyst, as reported in A. Gabrielsson, P. van Leeuwen, W. Kaim, Chem. Commun. 2006, 4926-4927. However, the catalyst showed fast decomposition under the reported reaction conditions.