Direct β-activation of saturated aldehydes to formal Michael acceptors through oxidative NHC catalysis.

Saturated carbonyl compounds, such as aldehydes and esters, are basic building blocks for the synthesis of organic molecules and materials. Reactions with carbonyl compounds as substrates primarily occur at the carbonyl carbon atom (as an electrophilic center) or the a-carbon atom (as a prenucleophile). In organocatalysis, several powerful approaches have been developed for the asymmetric functionalization of a-CH of aldehydes and esters. For example, many elegant transformations at the a-carbon atom of aldehydes have been realized by employing enamine or SOMO catalysis. Very recently, Rovis and co-workers and our laboratory independently reported a-carbon functionalization of saturated aldehydes through oxidative catalysis mediated by N-heterocyclic carbenes (NHCs). We have also realized NHCmediated a-functionalization of saturated esters. To functionalize the b-carbon atoms of carbonyl compounds, the corresponding a,b-unsaturated compounds are typically used. For example, several groups have developed NHC catalysis for the activation of a,b-unsaturated aldehydes (enals and a-bromoenals) and ynals, to form unsaturated esters or formal Michael acceptors. In particular, Studer pioneered the addition of 1,3-dicarbonyl compounds to a,b-unsaturated acyl triazoliums generated from a,bunsaturated aldehydes. Lupton and co-workers have recently pioneered the NHC-mediated activation of a,bunsaturated enol ester and acyl fluorides for eventual functionalizations of the b-sp carbon atoms. The enal bsp carbon atom can also be activated through iminium organocatalysis, as pioneered by MacMillan and co-workers. Several catalytic approaches are available for the direct activation of a-carbon atoms of carbonyl compounds (and bsp carbon atoms of unsaturated carbonyl compounds), but the direct activation of the typically inert b-C(sp) of saturated carbonyl compounds is challenging. Notably, C H activation involving the b-carbon atom of saturated esters and amides is pursued by several groups employing transitionmetal catalysis. In organocatalysis, the groups of Wang, Hayashi, and Enders have successfully oxidized the catalytically generated enamine intermediates to the corresponding a,b-unsaturated iminium species as Michael acceptors. Despite the impressive progress, catalytic direct b-activation of saturated carbonyl compounds has largely remained underdeveloped, and new strategies that contribute to this subject should be of broad interests. Here, we disclose the first direct activation of the b-C(sp) of saturated aldehydes through oxidative NHC catalysis (Scheme 1). The oxidation of Breslow intermediates to