Asymmetric Catalytic Construction of Fully-Substituted Carbon Stereocenters Using Acyclic α-Branched β-Ketocarbonyls: The “Methyl Rule” Widely Exists

The catalytic asymmetric construction of tetrasubstituted carbon stereocenters constitutes one of the most challenging research topics in organic synthesis, which further play vital roles in diverse fields including medicinal and material chemistry. In this context, the α-functionalization of β-ketocarbonyl compounds serves as one of the mostly used strategies to address the issue. Compared to cyclic β-ketocarbonyls, the catalytic asymmetric α-functionalization of acyclic β-ketocarbonyls is more difficult but has gained enough progress during the last several decades. This review illustrates the recent advances in this field, including acyclic α-branched β-ketocarbonyl-participated asymmetric fluorination, Michael additions, amination, aldol reaction, α-alkylation, α-alkynylation, α-oxygenation, Mannich reactions, etc. Furthermore, a thorough survey of all these reactions indicates the existance of a general principle which is called the “Methyl Rule”. Alternative methods that can complement the deficiency of the reports using direct asymmetric catalysis are also presented.