60th Annual Report on Research 2015

One electron reduction of isocyanates.  The remarkable utility of isocyanates (R−N=C=O) as building blocks for the production of more complex molecular systems has been recognized for well over 150 years.  Their greatest use has certainly been in the production of polyurethanes and polymer blends that contain cross-links of isocyanurate heterocycles (1).  These heterocycles are commonly produced from the reaction of three isocyanates that form a cyclic ring (e.g., cyclotrimerization).  In spite

of the extensive chemical research already performed using isocyanates and isocyanurates, there is very little known about the one electron reduction of either of these systems.  We have been particularly interested in generating isocyanate anion radicals for spectroscopic investigation to explore the similarities, if any, with the structure and the electron-spin distribution found in ketyls (e.g., RNCO^•− vs R₂CO^•−), which are possibly the most important and most investigated class of anion radicals.  Therefore, my motivation for exploring the chemistry of isocyanate anion radicals comes from the fact that a greater understanding of the structure and spectroscopy of these anion radical systems should lead to a more complete picture of how they can be used in syntheses.  My group has recently investigated the one electron reduction of both alkyl and phenyl isocyanates in dilute solution under ambient temperature conditions and found that the anion radical of the PhNCO can be generated and observed spectroscopically in polar aprotic solvents.  When the reduction is carried out in relatively non-polar solvents we find that the isocyanate anion radical rapidly cyclotrimerized resulting in the formation of a tri-substituted isocyanurate anion radical; this was found for both alkyl and phenyl isocyanates. 

My students and I continued to explore the one electron reduction of isocyanates with emphasis on systems that have p-conjugated rings attached to the NCO moiety. We utilize both electron paramagnetic resonance (EPR) spectroscopy and NMR spectroscopy as the principle analytical techniques in investigating these systems. Below, I briefly describe results obtained when investigating the reduction of two isocyanate systems: cyclooctatetraenyl isocyanate (COTNCO) and 1-naphthyl isocyanate (1-NapNCO). 

Cyclooctatetraenyl Isocyanate (COTNCO).  To further our understanding of the stability and the reactivity of isocyanate anion radicals, my group and I were motivated to investigate the one electron reduction of COTNCO (2).  The synthesis of 2

had not yet been reported.  Therefore, a former graduate student (Joseph Klen) and I developed a synthetic route to this new isocyanate starting with cyclooctatetraene.   We were interested in this system because of the high electron affinity of the [8]annulenyl moiety in 2. We anticipated that this would result in much of the electron density residing within the [8]annulenyl ring upon addition of an electron.  Since there is a fundamental quantum mechanical difference between COT (4n p electrons) and benzene (4n+2 p electrons), we believed the reduction of COTNCO would be an interesting choice to compare with the already explored PhNCO system.

The electron reduction of COTNCO was found to produce the corresponding isocyanurate species (3) (see Scheme 1). Unlike the previously studied tri-phenyl isocyanurate anion radical, the unpaired electron(s) was found to localize within a COT moiety attached to the isocyanurate ring. Further exposure to metal results in the formation of an equilibrium mixture of trianion triradical (4) and trianion radical (5a,b), see Scheme 1. The formation of 5a,b is a consequence of intramolecular disproportionation.  Interestingly, the COTNCO anion radical was never observed in these studies.  We believe this is a consequence of the favorable disproportionation of the anion radical to the COTNCO dianion. The additional charge (resulting

from the added second electron) would make the COT dianion a powerful nucleophile.   We proposed that this dianion drives the cyclotrimerization to form the isocyanurate species (3).  Remarkably, we found that exhaustive reduction of the tris-COT isocyanurate in THF generates the first-ever observed hexa-anion of an isocyanurate.  NMR analysis revealed that each of the three planar D_8h COT dianion moieties form tight ion pairs with two counter K⁺ ions (6).

1-Naphthyl Isocyanate (1-NapNCO).  As described above, my group has found that exposure of an alkyl or aryl isocyanate solution to an alkali metal (either potassium or sodium) is an effective and rapid method of cyclotrimerization leading to the generation of the respective isocyanurate. This process of isocyanurate formation has been proposed to proceed via the reactive isocyanate anion radical, formed from the one-electron reduction of the isocyanate, which rapidly attacks two more neutral isocyanates.  In the case of aryl isocyanates, this protocol is effective at converting phenyl isocyanate (PhNCO) and a number of para-substituted PhNCO compounds to their respective isocyanurates. However, prior to the studies with 1-NapNCO we had yet to determine the efficacy of converting isocyanates with bulky substituents attached to their respective cyclotrimers.  The one electron reduction experiments on this compound were performed by my former student Mark Kassabaum (MS, ‘12).  We determined that exposure of a solution containing 1-NapNCO did indeed result in the rapid cyclotrimerization to the respective isocyanurate in very good yield.  What was somewhat surprising to us initially is that two isomeric forms of the tris-(1-napthyl) isocyanurate are generated in the reaction.  Upon closer inspection we found that these isomers are diastereomers that can be classified further as atropisomers.  Atropisomers are two or more diasteroisomers generated as a result of hindered rotation of the bulky substituents attached.  In the case of tris-(1-naphthyl) isocyanurate, hindered rotation of the three naphthyl rings produces two diasteroisomers, which are easily distinguishable using NMR spectroscopic techniques.  Michael Nocella (BS ‘11) worked with me in the separation and purification of the two different diasteroisomers and he successfully grew single crystals of each for structural analysis via X-ray crystallography.  Shown below are the ORTEP diagrams of the two isomers (syn and anti), which are distinguishable by the orientation of the naphthyl rings.  Finally, in these studies we were able to detect a small amount of 1-NapNCO anion radical present in solution.  As in our previous studies, we proposed that this anion radical initiates and propagates the formation of the two atropisomers of the cyclotrimer.