The introduction of functional groups at the a carbon of carbonyl compounds is a common transformation in synthetic organic chemistry. a-Functionalized ketones are substructures found in many natural products, pharmaceuticals, and other functional organic compounds. The functionalization reaction relies on the inherent nucleophilicity of the a carbon of the enol (or enolate) derivative of the carbonyl compound, which reacts with an electrophilic reaction partner in this process. Many carbon-based electrophiles can be used, leading to the formation of C-C bonds, but the use of heteroatomic electrophiles becomes challenging. This is due to the high reactivity, and therefore limited functional-group compatibility of these species. They are typically strong oxidants, and this can lead to the formation of by-products, such as overfunctionalized or oxidized compounds. The structural variety of these species is also limited, and it is difficult to reconcile this with the idea of producing structurally diverse target compounds. Nevertheless, there are a number of heteroatomic electrophiles that can be used in such reactions, designed for specific transformations and with specific functional-group tolerances. An alternative approach is to use nucleophiles rather than electrophiles to react with enol derivatives. Iodine(III) compounds have been used in this context to mediate the coupling of the two nucleophilic reactants through twoelectron oxidations, thereby inverting the polarity of one of the reagents. This strategy has recently been termed "cross-nucleophile coupling". This area has evolved significantly since the first report. When it comes to heteroatomic nucleophiles, the reaction usually requires a Lewis acid, as well as a low reaction temperature, in a one-pot two-step procedure, to avoid formation of by-products (Figure ). First the I(III) reagent and the enol derivative react at low temperature to form an enolonium intermediate. This ensures that the enol nucleophile is consumed before the second nucleophile is added at higher temperature (Figure ). In this way, side reactions such as homocoupling of the enol derivative or a-functionalization with other nucleophiles derived from the I(III) reagent (e.g., OAc) are minimized. Using this protocol, Szpilman et. al elegantly observed O-enolonium species for the first time using 13 C NMR spectroscopy. The formation of by-products is closely related to the outstanding leaving ability of the I(III) functional group (10 6 better than triflate). In general, the nature of the second nucleophile is somewhat limited, but excellent results have been reported for arylations, azidations, cyanations, and acetoxylations. The somewhat narrow scope is partly due to the fact that the nucleophile may need to be incorporated into the structure of the I(III) reagent. General methods for the intermolecular reaction of ketones or enol derivatives with a variety of nucleophiles, using a non-designer I(III) reagent, are scarce. The Wirth group developed an effective approach to the formation of nitrogen-and oxygen-a-substituted ketones through an internal umpolung strategy mediated by PhI(OAc)2 (Figure ). Their strategy relied on the use of a tethered nucleophile, i.e., the nucleophile was attached to the silicon center of the enol ether substrate (Figure ). Importantly, they were able to extend the scope of the reaction to the synthesis of chiral a-substituted ketones when using chiral I(III) reagents. More recently, the Gulder group reported another elegant approach aimed at expanding the range of nucleophiles that can be used in such reactions. Here, 2-pyridyl ketones react by an umpolung coupling process mediated by a λ 3 -fluoro iodane (Figure ). It was proposed that a noncovalent interaction between the F atom in the iodane and the pyridine moiety in the ketone substrate plays a key role in this reaction. Although this reaction is quite limited in terms of the ketone structure, a large number of nucleophiles could be coupled. Considering the ketone component, the majority of reported examples, with the exception of the pyridyl ketones used by Gulder, rely on the use of silyl enol ethers. Our own group contributed to this area of research with an umpolung protocol using allylic alcohols as enol synthons, in a reaction mediated by iridium catalysts (Figure ). This method gave a-methoxy ketones from allylic alcohols, or 3(2H)-furanones from carbonyl-functionalized allylic alcohols. For all the examples, 1-fluoro-3,3-dimethyl-1,3-dihydro-1l 3 -benzo [d][1,2]iodaoxole was used as an oxidant. Figure 1. Strategies for the umpolung a-functionalization of ketones and enol derivatives. a) Cross-nucleophile coupling of silyl enol ethers with nitrogen nucleophiles. [7c] b) Intramolecular cross-nucleophile coupling of nucleophile-functionalized silyl enol ethers. c) Crossnucleophile coupling of pyridyl ketones. d) Cross-coupling of allylic alcohols with nucleophiles. d) This work: general method for the cross-nucleophile coupling of silyl enol ethers with nucleophiles.