Transition Metal-Catalyzed α-Position Carbon–Carbon Bond Formations of Carbonyl Derivatives

Abstract

α-Functionalization of carbonyl compounds in organic synthesis has traditionally been accomplished via classical enolate chemistry. As α-functionalized carbonyl moieties are ubiquitous in biologically and pharmaceutically valuable molecules, catalytic α-alkylations have been extensively studied, yielding a plethora of practical and efficient methodologies. Moreover, stereoselective carbon–carbon bond formation at the α-position of achiral carbonyl compounds has been achieved by using various transition metal–chiral ligand complexes. This review describes recent advances—in the last 20 years and especially focusing on the last 10 years—in transition metal-catalyzed α-alkylations of carbonyl compounds, such as aldehydes, ketones, imines, esters, and amides and in efficient carbon–carbon bond formations. Active catalytic species and ligand design are discussed, and mechanistic insights are presented. In addition, recently developed photo-redox catalytic systems for α-alkylations are described as a versatile synthetic tool for the synthesis of chiral carbonyl-bearing molecules.

Asymmetric Coupling of β-Ketocarbonyls and Alkynes by Chiral Primary Amine/Rh Synergistic Catalysis

“…Catalytic enantioselective α-alkylation of carbonyls is an enduring theme in chemical synthesis focusing on skeleton construction via C–C bond formation . Among various alkylation strategies, direct α-addition to unsaturated alkenes or alkynes represents one of the most desirable processes due to its high atom-efficiency .…”

Appealing Renewable Materials in Green Chemistry

“…Moreover, tremendous advances have been made in catalysis. Metals have contributed predominantly in the context of C-C bond formation [ 23 , 24 , 25 ] Hydrogenations and hydrations have also been thoroughly studied, [ 26 , 27 ] so intensively that it would be impossible to report them all in this review. Still, on this topic, the review mentioned above [ 22 ] comes to our rescue, proposing us a series of examples reported in the literature about new wool-mediated approaches.…”

Visible Light Assisted Radical‐Polar/Polar‐Radical Crossover Reactions in Organic Synthesis

“…α-alkylation of imine derivatives is one of the important strategies for the formation of CÀ C bond. [23] Masson's group demonstrated a 3-component alkylation strategy using enamides 9, diethyl bromomalonate 29, and alcohols in the presence of [Ir(ppy) 2 (dtbbpy)] PF 6 as a photocatalyst under 23 W fluorescent lamp to afford α-alkylated imine adducts 30 (Scheme 15). [24] The authors observed that a variety of protecting groups such as Cbz, Boc and Alloc, etc, were well tolerated under standard conditions.…”