The Proline‐Catalyzed Mannich Reaction and the Advent of Enamine Catalysis

Cooperative Triple Catalysis Enables Deaminative α-Indolmethylation of Carbonyl Compounds with Gramines

“…Owing to the low chemical reactivity of α-H, the classical α-functionalization (halogenation, aldol condensation, alkylation, and Mannich reaction) of carbonyl compounds requires harsh reaction conditions. Enamine catalysis reacts amines with carbonyl compounds to form enamine compounds and activate the α-position of carbonyl compounds, thus simplifying their α-functionalization . Recently, the cooperative transition-metal/enamine catalysis has gained significance as a strategy for the α-functionalization of carbonyl compounds, thereby expanding its scope .…”

Deployment of Sulfinimines in Charge-Accelerated Sulfonium Rearrangement Enables a Surrogate Asymmetric Mannich Reaction

“…Although asymmetric Mannich reactions with easily enolizable carbonyl compounds or the corresponding enolate equivalents have been established, owing to the high α-C–H p K a values of amides (p K a around 35), chemoselective enolate formation becomes an almost insurmountable barrier in these cases (Scheme B). This renders the classical Mannich reaction a highly challenging prospect for this critical class of donors, and, to this date, successful direct Mannich reactions of carboxamides mostly rely on designer amides bearing a 1-acyl-7-azaindole moiety. ,, Recently, the Kobayashi group developed a catalytic system enabling asymmetric Mannich reactions of aldimines with amides .…”

Chiral Metal Salts as Ligands for Catalytic Asymmetric Mannich Reactions with Simple Amides

“…Catalytic asymmetric Mannich reactions of imines with amides and esters are one of the most powerful and atom-economical methods to provide optically active β-amino acid derivatives without any redox process. − To date, although several catalytic asymmetric Mannich reactions with easily enolizable carbonyl compounds such as aldehydes and ketones (p K a ≤ 30 in DMSO) have been developed, − the reactions with amides and esters without any electron-withdrawing groups at their α-positions (p K a ≥ 30 in DMSO) have been unsuccessful. − The most commonly employed methods still utilize preformed metal/metalloid enolates such as lithium enolates and ketene silyl acetals, which generate significant amounts of waste. Recently, Shibasaki and Kumagai et al reported catalytic asymmetric Mannich reactions with 1-acyl-7-azaindoles as well-designed amides. − In these reactions, many kinds of 1-acyl-7-azaindoles were available as acyl donors, while a 7-azaindole part was always required to obtain high reactivity and stereoselectivity.…”