Multicomponent Mannich‐Like Reactions of Organometallic Species

Abstract

A century after the pioneering works of Carl Mannich in 1917, the aminoalkylation of carbonylated compounds has become a classical reaction of organic chemistry. Thanks to its modular character, the so-called multicomponent Mannich reaction has found numerous applications throughout the fields of chemistry, especially for synthetic and biomedical purpose. After 100 years of good service, recent developments involving

Hf(OTf)4 as a Highly Potent Catalyst for the Synthesis of Mannich Bases under Solvent-Free Conditions

“…With the optimized conditions, 0.5 mol% Hf(OTf) 4 was applied to the synthesis of a diversity of aryl ketone-derived β-amino carbonyl compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). As shown in Scheme 1, the current method exhibits good generality to a variety of substrates, and the aryl ketone-derived Mannich bases were obtained in excellent yields (87-94%) within 4-7 h. Electron-donating and electron-withdrawing substituents at the ortho, meta, and para positions of the phenyl rings of ketone, aldehyde, and aniline are well tolerated by this method.…”

“…Mannich reaction has been recognized as one of the most classic multicomponent reactions (MCRs) and utilized for the synthesis of β-amino carbonyl compounds (Mannich bases) via one-pot condensation-addition of aldehyde, amine, and ketone since its discovery in 1917 [1]. Mannich bases are versatile synthetic intermediates [2][3][4][5] and widely applied in the synthesis of natural products [6] and pharmaceutical chemistry [7,8].…”

CoI‐Catalyzed Barbier Reactions of Aromatic Halides with Aromatic Aldehydes and Imines

“…The formation of this latter could be explained by aO ppenauer oxidation of 6a by the startinga ldehyde 5,a sp reviously observed in electrochemical NHK couplings. [23] To expand the usefulness of the present Co II /Zn catalytic system,w ew ondered if it might be suitable for other electrophiles, such as imines.I ndeed, the reductiveB arbier coupling of an aromatich alide and as ulfonyli mine would provide an alternative to organometallic Mannich reactions, [24][25][26] which usually requiret he use of as toichiometric strong reductant such as Mn. [27] We thus applied the standard conditions to a varietyofa ryl halidesand imines, and the resultshavebeen reportedi nT able 3.…”

Multicomponent Aromatic and Benzylic Mannich Reactions through C−H Bond Activation

“…Indeed, in addition to a straightforward access to nitrogen‐containing scaffolds, the Mannich reaction constitutes a fundamentally powerful C−C and C−N bond forming reaction, due to the opportunity of operating under multicomponent conditions using simple and varied starting materials . Apart from the classical aminoalkylation of carbonyl compounds using enols and enolates (Scheme A), recent improvements of the reaction have focused on the use of other nucleophiles such as organometallic species, thus contributing to greatly expand the usefulness of this class of reactions (Scheme B) . Nevertheless, this strategy usually relies on the use of halides and stoichiometric amounts of metals thus producing large amounts of wastes.…”

“…[4] Apart from the classical aminoalkylation of carbonylc ompounds using enols ande nolates( Scheme1A),r ecent improvements of the reactionh ave focusedo nt he use of other nucleophiless uch as organometallic species, thus contributing to greatlye xpand the usefulness of this class of reactions (Scheme 1B). [5] Nevertheless, this strategy usually relies on the use of halides and stoichiometric amounts of metals thus producing large amountsofw astes.…”