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Reports: ND351971-ND3: Metal-Free Activation of Nitrogen Oxides for Hydrocarbon Functionalization

Timothy H. Warren, Georgetown University

This grant has allowed our laboratory to explore the reactivity of intramolecular “frustrated Lewis pairs” (FLPs) with nitric oxide (NO) and other small molecule substrates.  FLPs are combinations of Lewis bases and acids that resist the formation of a strong, intramolecular donor-acceptor interaction due to significant steric bulk at the Lewis basic and acidic components.  This pent up reactivity is unleashed on small molecules such as H2, CO2, and N2O that may be captured between the Lewis base and acid.1 In close collaboration with Professor Erker at the University of Münster, Germany, our laboratory has examined phosphino-boranes such as Mes2PCH2CH2B(C6F5)2 to capture radical species such as nitric oxide (NO).2-4  Such intramolecular PB-FLP systems rapidly and irreversibly capture NO to provide PB-FLP-NO as five-membered heterocycles with new P-NO and B-NO bonds. These species are reminiscent of organic nitroxides such as TEMPO since a significant amount of unpaired electron density is shifted to the O atom of the captured NO moiety.  These O-centered radical species are potent H-atom abstracting reagents due to the strong O-H bond formed in the reduced hydroxylamine species PB-FLP-NOH.2 As such, they react with hydrocarbons such as ethylbenzene to generate new C-O bonds to the O-atom of the captured NO moiety. 

The strong donor ability of phosphine Lewis bases enables P-based oxidation to phosphine oxides in the presence of NO. Reaction of 2 equiv. NO with the intermolecular  tBu3P / B(C6F5)3 system results in formation of a 1:1 mixture of tBu3P-N2O-B(C6F5)3 and tBu3P-O-B(C6F5)3.2  The use of linked, intramolecular PB-FLPs such as Mes2PCH2CH2B(C6F5)2, however, allows for isolation of the PB-FLP-NO species.  Experimental and theoretical studies point to strong binding of NO by these electron-rich systems enabling their use as nitroxide-like species for H-atom abstraction reactions.  In conjunction with the Erker group, we have examined a wide range of PB-FLP-NO species that consistently engage in H-atom abstraction reactions.  A recent review places the capture of NO by PB-FLP systems in context with other 1,1-addition reactions of other unsaturated systems such as isocyanides CNR, carbon monoxide CO, and organoazides N=N=NR.5

To reduce the possibility of phosphine oxidation as well as to render the FLP-NO interaction more labile, we turned to the use of intramolecular imine-borane systems NB-FLP.  We were inspired by Prof. Stephan’s hydroboration of carbodiimides RN=C=NR with HB(C6F5)2 that gave rise to four-membered boron amidinates that serve as frustrated Lewis pairs.6  While these boron amidinates react slowly with FLP-type substrates such as CO2 and CNR to give six- and five-membered heterocycles, they react quite slowly.  The strong donor ability of each RN unit (R = tBu or iPr) makes it difficult to achieve an “open” structure.6  Thus, we were not surprised when we found that these boron amidinates did not capture NO.

To address some of these limitations and generate new families of intramolecular NB-FLPs, we turned to hydroboration of isocyanates ArN=C=O.  The reaction of HB(C6F5)2 with ArN=C=O (Ar = 2,6-iPr2C6H3) leads to FLP-type intermediates capable of rapidly capturing the isocyanate ArNCO as well as acetonitrile MeCN to form six-membered heterocycles.  While these species react as FLPs, we cannot isolate the “free” boron formamidate FLP. Fortunately, the ArNCO interaction appears to be labile, offering access to the “free” NB-FLP in solution that  may trap NO as judged by a characteristic EPR spectrum observed upon addition of NO to the isocyanate adduct.  We are exploring hydroboration of very large isocyanates Ar’NCO to discourage capture of an additional equivalent of Ar’NCO to allow structural characterization of the active NB-FLP species.7 

Lastly, we have embarked on a deceptively simple approach to understanding bonding in organonitroso compounds RSNO.  Due to the low RS-NO homolytic bond dissociation energy (20-32 kcal/mol), S-nitrosothiols serve as NO donors.  Importantly, addition of a strong Lewis acid to the O-atom of an S-nitrosothiol RSNO has been predicted to enhance the RS+=N-O- resonance structure, leading to a lengthened N-O bond, a shortened N-S bond, and enhanced electrophilicity at S. Thus, we have begun to explore reactions of RSNOs with simple Lewis acids such as B(C6F5)3 as well as the PB-FLP and NB-FLP systems described above.  Due to the strong B-O interaction identified in the NB-FLP systems above, we anticipate that the O-atom of RSNOs will engage at the Lewis acid which is borne out in preliminary experiments.

 

References

1.         (a) Stephan, D. W. "Discovery of Frustrated Lewis Pairs: Intermolecular FLPs for Activation of Small Molecules" Top. Curr. Chem. 2013, 332, 1-44. (b) Kehr, G.; Scwendemann, S.; Erker, G. "Intramolecular Frustrated Lewis Pairs: Formation and Chemical Features" Top. Curr. Chem. 2013, 332, 45-84.

2.         “Capture of NO by a Frustrated Lewis Pair: A New Type of Persistent N-Oxyl Radical” Cardenas, A. J. P.; Culotta, B. J.; Warren, T. H.; Grimme, S.; Stute, A.; Fröhlich, R.; Kehr, R.; Erker, G. Angew. Chem. Int. Ed. 2011, 50, 7567-7571.

3.         Sajid, M.; Stute, A.; Cardenas, A. J. P.; Culotta, B. J.; Hepperle, J. A. M.; Warren, T. H.; Schirmer, B.; Grimme, S.; Studer, A.; Daniliuc, C. G.; Fröhlich, R.; Petersen, J. L.; Kehr, G.; Erker, G. “N,N-Addition of Frustrated Lewis Pairs to Nitric Oxide: An Easy Entry to a Unique Family of Aminoxyl Radicals” J. Am. Chem. Soc. 2012, 134, 10156-10168.

4.         Warren, T. H.; Erker, G. “Radical Frustrated Lewis Pairs” Top. Curr. Chem. 2013, 334, 219-238.

5.         Cardenas, A. J. P.; Hasegawa, Y.; Kehr, G.; Warren, T. H.; Erker, G. “Cooperative 1,1-addition reactions of vicinal phosphane/borane frustrated Lewis pairs” Coord. Chem. Rev. 2015  doi: 10.1016/j.ccr.2015.01.006.

6.         Dureen, M. A.; Stephan, D. W. “Reactions of Boron Amidinates with CO2 and CO and Other Small Molecules” J. Am. Chem. Soc. 2010, 132, 13559-13568.

7.         McQuilken, A. C.; Cardena, A. J. P.; Warren, T. H. “Synthesis and Reactivity of a New Class of Frustrated Lewis Pairs” Fall 2015 National Meeting of the ACS Meeting, Boston, MA, August 16-20, 2015. INOR

8.         Talipov, M. R.;  Timerghazin, Q. K. “Protein Control of S‐Nitrosothiol Reactivity: Interplay of Antagonistic Resonance Structures” J. Phys. Chem. B 2013, 117, 1827-1837.