58th Annual Report on Research 2013 Under Sponsorship of the ACS Petroleum Research Fund

The simplest stable free radical with one unpaired electron, nitric oxide plays important roles in industry, the environment and biology.  Nitric oxide (NO) is produced a multi-million ton scale worldwide each year by the oxidation of anhydrous ammonia, serving as an intermediate converted to nitric acid in the Ostwald process.  Despite its massive scale of industrial production, NO has relatively limited direct synthetic applications, especially considering its high degree of unsaturation.  NO serves as an important ligand in transition metal chemistry that engages in a wide range of reactivity. Nonetheless, there are relatively few classes of transition metal promoted reactions in which NO serves as a building block to selectively form new bonds to carbon.           

This project seeks to identify new, metal-free approaches for nitric oxide utilization through the use of frustrated Lewis pairs (FLPs).  FLPs are potent combinations of a Lewis acid and a Lewis base that are sterically prohibited from forming a strong interaction.  Instead, this reactive potential may be directed on an additional small molecule that binds to the FLP. For instance, Prof. Doug Stephan now at the University of Toronto has shown that the intermolecular FLP ^tBu₃P / B(C₆F₅)₃ cleaves H₂ to give [^tBu₃P-H]⁺ [H-B(C₆F₅)₃]^- and unsaturated substrates such as ethylene form zwitterionic adducts such as ^tBu₃P⁺-CH₂CH₂-^-B(C₆F₅)₃.

In collaboration with Professor Erker at the University of Münster, we have employed the intramoleculear FLP Mes₂PCH₂CH₂B(C₆F₅)₂ (PB-FLP) to capture nitric oxide.  A five-membered heterocycles results with new P-N and B-N bonds.  Importantly, the nitric oxide moiety undergoes a spin density Umpolung, shifting unpaired electron density from N in free NO (N: 0.71 e^-, O: 0.29 e^-) to O in PB-FLP-NO (N: 0.54 e^-, O: 0.34 e^-), supported by EPR spectra and high level calculations by collaborator Prof. Stefan Grimme now at Bonn University.  The resulting PB-FLP-NO species resembles common nitroxides such as TEMPO, but is considerably more reactive due to the stronger PB-FLP-NO-H bond (ca. 77 kcal/mol) vs. TEMPO-H (ca. 67 kcal/mol) that results from stronger spin polarization towards O in FLP-NO.

This substantially higher O-H bond strength in PB-FLP-NO allows for ready H-atom abstraction (HAA) / radical recombination (RR) reactions with allylic and benzylic hydrocarbons R-H such as cyclohexene and ethylbenzene that give the corresponding PB-FLP-NO-H species with formation of a radical R• that is rapidly captured by an additional equivalent of PB-FLP-NO to give PB-FLP-NO-R species.  Importantly, this reaction occurs at room temperature!  We have measured second order rate constants on the order of 10^-4 to 10^-5 M^-1s^-1 to quantify the allylic and benzylic C-H functionalization performed by this FLP-captured form of NO.  This finding was surprising and rewarding: non-metals can significantly activate nitric oxide toward hydrocarbon functionalization, a reaction that normally requires very forcing conditions (>200 °C or higher) for free NO alone.

Follow up studies have shown that a wide range of PB-FLPs can trap NO to give PB-FLP-NO species capable of HAA / RR with toluene (benzylic C-H BDE = 90 kcal/mol).  In a collaborative report, Prof. Armido Studer at the University of Münster show that and that this new class of N-oxyl radicals can serve as mediators in the nitroxide mediated polymerization of styrene.

Future studies planned involve reactions with NO₂ to identify new, metal-free pathways for the abatement of this environmental pollutant as well as the use of new FLPs featuring frustrated N^…B interactions which may lead to milder, more reversible activation of NO.  This grant has enabled our lab to examine chemistry free from metals, supporting graduate student Allan Cardenas who first discovered and examined this novel metal-free capture and activation of nitric oxide.  Furthermore, it has enabled rich international collaborations with the Erker, Grimme, and Studer research groups in Germany, expanding the reach of the science we perform at Georgetown.