The Oxidative Mannich Reaction Catalyzed by Dirhodium Caprolactamate.

Abstract

Dirhodium caprolactamate [Rh 2 (cap) 4 ] is a highly effective catalyst for the oxidative Mannich reaction. The reaction proceeds via C-H oxidation of a tertiary amine followed by nucleophilic capture. This green transformation is conducted in protic solvent using inexpensive T-HYDRO ® (70% t-BuOOH in water). Synthetically valuable γ-aminoalkyl-butenolides are obtained.The Mannich reaction remains a fundamentally important carbon-carbon bond forming reaction in organic synthesis. 1 Access to valuable Mannich addition products is made possible via reactive iminium ions that undergo capture with a rich assortment of nucleophiles. However, despite its well-documented scope and utility, methods for the formation of iminium ions remain limited. Strategies such as condensation or α-fragmentation often require harsh

Oxidative Mannich Reactions of Tertiary Amines Using a Cu(II) 2-Quinoxalinol Salen Catalyst

“…Next, we looked at the regioselectivity for the formation of the iminium ion when the disubstituted N-methyl, N-ethyl aniline is used as the substrate. 10 The coupling was found to happen exclusively on the methyl carbon, giving rise to 4g in a 62% yield. These results are consistent with the reported acidity values by Mariano and co-workers in reactions with aniline derivatives.…”

“…In 2006, a dirhodium caprolactamate catalyst was used for the oxidation of tertiary amines to iminium ions (as shown in Scheme 1a). 10 Yields up to 95% could be obtained when using 2-triisopropoxysilylfuran as the nucleophile; however, these reactions required the expensive rhodium complex as catalyst. In 2010, the simple copper salt CuBr (5 mol %) was used by Huang and co-workers for oxidative Mannich reactions, producing modest yields from 52 to 78% with indole as the nucleophile in the Mannich coupling reaction (Scheme 1b).…”

“…Coupling of the α-amino radical and t-butylperoxy radical forms intermediate 5, which can be isolated and identified by NMR using a non-nucleophilic solvent such as DCM. 10 However, when MeOH is used, it displaces the t-butylperoxy group to form 6. This then leads to the formation of the electrophilic iminium ion upon elimination of MeOH.…”