Transition‐Metal‐Catalyzed Aminooxygenation of Alkenes

Abstract

Alkene aminooxygenation reactions provide vicinal amino alcohol derivatives, moieties that frequently appear in catalysts, drugs, and other valuable molecules. This Chapter reviews transition‐metal‐catalyzed aminooxygenations of alkenes and aims to serve as a guide in the selection of appropriate reagents and procedures for specific substrate classes and desired transformations. Inter‐ and intramolecular aminooxygenation reactions catalyzed by osmium, palladium, platinum, gold, copper, iron, iridium, rhodium, ruthenium, and manganese are presented, as is a discussion of the factors involved in reactivity and selectivity. A brief section on non‐metal catalyzed alkene aminohydroxylation is also included. A complete set of alkene aminooxygenation reactions through mid‐2020 is provided in the Tabular Survey.

Copper-Catalyzed Enantioselective Aerobic Alkene Aminooxygenation and Dioxygenation: Access to 2-Formyl Saturated Heterocycles and Unnatural Proline Derivatives

“…When the catalyst consisting of CuCl complexed to ( R,R )-Ph-Box ( L1 ) was applied, the aminooxygenation occurred in 25% isolated yield and 44% ee (Table , entry 1) . Under these conditions (PhCH 3 , 120 °C, 24 h), the remainder of the mass balance was composed of a sultam side product that arises from radical addition to the sulfonamide arene , and overoxidation of the aldehyde to its C–C bond cleaved lactam (these compounds were obtained as major adducts under slightly different conditions, see the middle equation, Scheme A). ,, We hypothesized that the poor enantioselectivity could be the result of the tight-binding chloride ligand, distorting the enantiodetermining aminocupration transition state . Addition of AgOTf to sequester the chloride ion did result in an increase in ee from 44 to 63% (Table , entries 1 and 2).…”

“…Alkene difunctionalization is a powerful bond-forming transformation that can increase molecular complexity and install useful functional groups regio- and stereoselectively. The field has undergone a tremendous renaissance in the past few decades, fueled in part by the significant interest in replacing toxic and rare metal catalysts with more environmentally friendly and earth-abundant ones. − Among the many alkene difunctionalization variations, the aminooxygenation, − providing vicinal amino alcohols and derivatives, and the diooxygenation, − toward vicinal diols and derivatives, are prominent. We report herein a catalytic enantioselective approach to the synthesis of 2-formyl pyrrolidines and 2-formyl cyclic ethers from their corresponding alkenyl sulfonamides and alkenols, respectively.…”

Acid-Catalyzed Oxy-aminomethylation of Styrenes

“…Olefins are abundant and inexpensive starting materials for chemical synthesis. Consequently, the chemistry of alkene functionalization has received much attention in the last century, which has led to the development of fundamental reactions such as the Ziegler–Natta polymerization, the Diels–Alder cycloaddition, or the Mizoroki–Heck reaction, and hydrogenations, to just name a few. − The direct heterofunctionalization of CC bonds is a particularly powerful strategy for the transformation of feedstock chemicals into highly functionalized compounds, as exemplified by reactions such as dihydroxylation and aminohydroxylation, hydroamination, and many others. − From these type of transformations, the Prins reaction and the aza-version thereof stand out for enabling the direct synthesis of 1,3-difunctionalized moieties, which are widely present in pharmaceutically relevant molecules . The Prins reaction has been extensively documented, and several catalytic methodologies are available nowadays. , Analogously, the aza-Prins reaction of an alkene, formaldehyde, and ammonia represents a straightforward approach to transform olefins into 1,3-amino alcohols.…”

Cu-Catalyzed Double C(sp3)–H Functionalization of Ethylarenes to Form Arylethanolamines

“…They are also used as intermediates for the synthesis of chiral auxiliaries and ligands . Numerous methods have been developed for their syntheses, particularly from vinylarenes as starting materials . Typically, vinylarenes are oxidized to form the corresponding epoxides, which are subjected to the reaction with amines, and thus, two steps are required (Figure b) .…”