Posts Tagged ‘radical chains’
Organometallic chemistry has vastly expanded the practicing organic chemist’s notion of what makes a good nucleophile or electrophile. Pre-cross-coupling, for example, using unactivated aryl halides as electrophiles was largely a pipe dream (or possible only under certain specific circumstances). Enter the oxidative addition of polarized bonds: all of a sudden, compounds like bromobenzene started looking a lot more attractive as starting materials. Cross-coupling reactions involving sp2– and sp-hybridized C–X bonds beautifully complement the “classical” substitution reactions at sp3 electrophilic carbons. Oxidative addition of the C–X bond is the step that kicks off the magic of these methods. In this post, we’ll explore the mechanisms and favorability trends of oxidative additions of polar reagents. The landscape of mechanistic possibilities for polarized bonds is much more rich than in the non-polar case—concerted, ionic, and radical mechanisms have all been observed.
Oxidative additions of aryl and alkenyl Csp2–X bonds, where X is a halogen or sulfonate, proceed through concerted mechanisms analogous to oxidative additions of dihydrogen. Reactions of N–H and O–H bonds in amines, alcohols, and water also appear to be concerted. A π complex involving η2-coordination is an intermediate in the mechanism of insertion into aryl halides at least, and probably vinyl halides too. As two open coordination sites are necessary for concerted oxidative addition, loss of a ligand from a saturated metal complex commonly precedes the actual oxidative addition event.
Over the years, a variety of “quirky” substitution methods have been developed. All of these have the common goal of facilitating substitution in complexes that would otherwise be inert. It’s an age-old challenge: how can we turn a stable complex into something unstable enough to react? Photochemical excitation, oxidation/reduction, and radical chains all do the job, and have all been well studied. We’ll look at a few examples in this post—remember these methods when simple associative or dissociative substitution won’t get the job done.
Substitution reactions of dative ligands—most famously, CO—may be facilitated by photochemical excitation. Two examples are shown below. The first reaction yields only monosubstituted product without ultraviolet light, even in the presence of a strongly donating phosphine.
All signs point to dissociative mechanisms for these reactions (the starting complexes have 18 total electrons each). Excitation, then, must increase the M–L antibonding character of the complex’s electrons; exactly how this increase in antibonding character happens has been a matter of some debate. Originally, the prevailing explanation was that the LUMO bears M–L antibonding character, and excitation kicks an electron up from the HOMO to the LUMO, encouraging cleavage of the M–L bond. A more recent, more subtle explanation backed by calculations supports the involvement of a metal-to-ligand charge-transfer state along with the “classical” ligand-field excited state.
Imagine a screaming baby without her pacifier—that’s a nice analogy for an odd-electron organometallic complex. Complexes bearing 17 and 19 total electrons are much more reactive toward substitution than their even-electron counterparts. Single-electron oxidation and reduction (“popping out the pacifier,” if you will) can thus be used to efficiently turn on substitution. As you might expect, oxidation and reduction work best on electron-rich and electron-poor complexes, respectively. The Mn complex in the oxidative example below, for instance, includes a strongly donating MeCp group (not shown).