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

Timothy H. Warren, Georgetown University

We have been exploring metal-free approaches to capture nitric oxide and other nitrogen oxides through the use of intramolecular “frustrated Lewis pairs” (FLPs).  These combinations of sterically demanding Lewis bases and acids resist the formation of a strong, intramolecular donor-acceptor interaction, focusing their reactive potential on small molecules such as H2, CO2, and N2O that may be captured between the Lewis base and acid.1  Collaborating closely 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  We find that NO is rapidly and irreversibly captured to provide PB-FLP-NO species which exhibit a five-membered heterocycle with new P-N and B-N bonds that reminiscent of nitroxides: a significant amount of unpaired electron density is shifted to the O atom of the captured NO moiety.  This new radical species exhibits enhanced H-atom abstracting ability compared to typical nitroxides such as TEMPO due to the strong O-H bond formed in the reduced hydroxylamine species PB-FLP-NOH.2

As part of our studies to employ NO as an oxidant in this metal-free approach, we have examined in greater detail the ability of NO to oxidatively transform phosphino-borane FLPs.  For instance, our first report in 2011 described the use of the intermolecular tBu3P / B(C6F5)3 system which reacts with NO to form a 1:1 mixture of tBu3P-N2O-B(C6F5)3 and tBu3P-O-B(C6F5)3 which mirrors the oxidation of a phosphine R3P by 2 equiv. NO to give R3P=O and N2O.2  Engagement of a phosphine in a FLP-type of interaction is necessary to prevent irreversible oxidation of the phosphine.  For instance, the PB-FLPs 1 and 2 that each possess an unsaturated backbone with cis-phosphino and borane substituents leads to a relatively strong intramolecular donor-acceptor interaction due to the enhanced conformational rigidity as compared to unsaturated systems such as Mes2PCH2CH2B(C6F5)2 (Scheme 1).5  As such, the PMes2 substituent of these bis(phosphine) FLPs 1 and 2 does not interact with the B center.   Upon exposure to NO, this non-interacting phosphino unit becomes oxidized to the corresponding phosphine oxide to give 3 and 4.  The Lewis acid “protected” phosphine moiety actually takes part in the FLP capture of NO for form the PB-FLP-NO adducts 5 and 6.  This is likely assisted through the loosening of the vinyl phosphine-borane interaction due to transient coordination of the newly formed phosphine-oxide to the borane.  Notably, NO capture is not observed by a closely related vinyl phosphino-borane 7 that does not possesses the phosphine-oxide donor.5

As a result of these studies, we have launched a synthetic investigation of new nitrogen-based intramolecular NB-FLPs that bear a sterically disrupted imine-borane interaction for NO capture and subsequent hydrocarbon activation.  We anticipate these NB-FLPs will be significantly more resistant to oxidation.  Owing to the higher electronegativity of nitrogen, amines or imines are much less prone oxidation to amine N-oxides or oxaziridines than the oxidation of a phosphine to the corresponding phosphine oxide.  We will share our findings in the next annual report.

We have also begun to explore the ability of PB-FLP systems to capture radicals other than NO.  Given the ability of PB-FLP systems to capture nitrosobenzene in a k2-NO fashion,6 we anticipate that a related k2-CO coordination mode may be possible for acyl radicals •C(O)R.  We examined the reaction of alkyl- and aryl-substitued acyl chlorides RC(O)Cl with the intramolecular PB-FLP system Mes2PCH2CH2B(C6F5)2.  This leads to the acylation of the phosphine leading to the zwitterion 8 in which the Cl atom was captured to generate a borate center (Scheme 2).7  Interestingly, when this reaction is carried out with alkyl acyl chlorides that bear an a-C-H group, the acyl chloride undergoes net 1,1-dehydrohalogenation to provide novel PB-FLP captured ketene 9 along with an equilvalent of the phosphonium borate zwitterion 10 bearing the removed HCl (Scheme 3).9 Future efforts will involve the conversion of aroylphosphonium-chloroborate species such as 9 to the corresponding PB-FLP captured acyl radical via 1-electron reduction chemistry.

This grant has enabled our lab’s first efforts to combine C-H functionalization and nitric oxide chemistry in a context free from metals.  Furthermore, it has enabled rich international collaborations with the Erker research group in Münster, Germany, as well as computational collaborations with Prof. Stefan Grimme’s research group in Bonn, Germany.  These activities have also involved student exchanges.  For instance, Erker PhD student Silke Frömel spent three months at Georgetown during Fall 2013 when she outlined the chemistry between acyl halides and the PB-FLP Mes2PCH2CH2B(C6F5)2.

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.         “N,N-Addition of Frustrated Lewis Pairs to Nitric Oxide: An Easy Entry to a Unique Family of Aminoxyl Radicals” 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. J. Am. Chem. Soc. 2012, 134, 10156-10168.

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

5.         “Frustrated Lewis Pair Modification by 1,1-Carboboration: Disclosure of a Phosphine Oxide Triggered Nitrogen Monoxide Addition to an Intramolecular P/B Frustrated Lewis Pair” Liedtke, R.; Scheidt, F.; Ren, J.; Schirmer, B.; Cardenas, A. J. P.; Daniliuc, C. G.; Eckert, H.; Warren, T. H.; Grimme, S.; Kehr, G.; Erker, G. J. Am. Chem. Soc. 2014, 136, 9014–9027.

6.         “P/B Ketene Adduct Formation from Acyl Chlorides at a Vicinal Phosphane/Borane Frustrated Lewis Pair” Frömel, S.; Radermacher, G.; Wibbeling, B.; Daniliuc, C. G.; Warren, T. H.; Kehr, G.; Erker, G. Isr. J. Chem. 2014 doi: 10.1002/ijch.201400133.