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DOI: 10.1055/sos-SD-204-00115

MacMillan, D. W. C.; Beeson, T. D.Science of Synthesis: Asymmetric Organocatalysis, (20121273.

Carbonyl CC bond α-functionalizations have long been a fundamental area of active chemical research. Catalytic enantioselective methods for carbonyl α-alkylations,[‌29‌‌31‌] -allylations,[‌32‌,‌33‌] -vinylations,[‌34‌,‌35‌] and -arylations[‌36‌‌40‌] have historically and until recently predominantly utilized preactivated enolates, enol carbonates, or keto esters, and often generate quaternary stereocenters that are resistant to epimerization. Enamine catalysis has enabled a plethora of methods for the direct enantioselective α-functionalization of aldehydes and ketones,[‌1‌,‌2‌] but until recently, alkylation events using the enamine platform were lacking[‌41‌] due to the necessary use of alkyl electrophiles that prefer to alkylate the amine catalyst, and also the preponderance for aldehyde dimerization. These challenges are overcome in the SOMO catalysis platform by umpolung reversal of the reactivity of the reaction components, thereby negating catalyst inhibition and enamine-based side reactions. Although not discussed in this chapter, the challenges to enamine-based α-alkylations have very recently been overcome through the use of photoredox-generated alkyl and aryl radicals,[‌42‌‌44‌] iodonium salts,[‌45‌,‌46‌] and carbocations[‌47‌‌49‌] as electrophiles in enamine-catalyzed alkylations.