Tetrahydropyridines via FeCl₃-Catalyzed Carbonyl–Olefin Metathesis

Abstract

Herein we describe the application of Lewis-acidcatalyzed carbonyl−olefin metathesis toward the synthesis of substituted tetrahydropyridines from commercially available amino acids as chiral pool reagents. This strategy relies on FeCl 3 as an inexpensive and environmentally benign catalyst and enables access to a variety of substituted tetrahydropyridines under mild reaction conditions. The reaction proceeds with complete stereoretention and is viable for a variety of natural and unnatural amino acids to provide the corresponding tetrahydropyridines in up to 99% yield.Letter pubs.acs.org/OrgLett

Superelectrophilic Fe(III)–Ion Pairs as Stronger Lewis Acid Catalysts for (E)-Selective Intermolecular Carbonyl–Olefin Metathesis

“…In recent years, carbonyl–olefin metathesis reactions have seen increased interest as a result of their ability to directly form carbon–carbon bonds between carbonyl and olefin functionalities. − Lewis-acid-catalyzed approaches have been developed as part of these efforts and undergo an initial [2 + 2]-cycloaddition to form intermediate oxetanes and a subsequent retro-[2 + 2]-cycloreversion to yield the corresponding carbonyl–olefin metathesis products . On the basis of this design principle, viable procedures for carbonyl–olefin ring-closing and ring-opening metatheses, as well as transannular carbonyl–olefin metathesis, have been reported that proceed through oxetane intermediates. − Additional approaches to intermolecular carbonyl–olefin cross-metathesis exist, relying on either zeolites or carbocations as organocatalysts. ,, In comparison with olefin–olefin cross-metathesis, the currently available protocols for carbonyl–olefin cross-metathesis reactions remain significantly underdeveloped. We herein report studies toward an intermolecular carbonyl–olefin cross-metathesis reaction between aromatic aldehydes 6 and olefins 7 that relies on superelectrophilic Fe­(III)–ion pairs as stronger Lewis acid catalysts.…”

Iodine-Catalyzed Synthesis of Substituted Furans and Pyrans: Reaction Scope and Mechanistic Insights

“…Schindler and co-workers subsequently identified FeCl 3 as an efficient Lewis acid-based catalyst for the formation of a range of 3,4-dihydro-2 H -pyrans and 3-carboxy-2,5-disubstituted furans . This simple catalyst also proves to be an efficient promoter for the intramolecular carbonyl–olefin metathesis reaction in a series of elegant studies by the same group . The similarity in catalytic activity between FeCl 3 and iodine, demonstrated by these studies and our earlier work (Scheme ), prompted us to investigate the possibility of using molecular iodine as a catalyst for the synthesis of a broader scope of pyrans and furans.…”

Carbonyl–Olefin Metathesis

“…121 The Schindler group reported in 2020 the FeCl 3 -catalyzed formation of functionalized tetrahydropyridines 436. 118 Amino acids serve as chiral pool reagents to access N-containing aryl ketones 434 using a variety of electron-poor sulfonamide protecting groups (Scheme 75). Electron-deficient tosylamides functioning as protecting groups for the secondary amines were identified as superior and utilized to promote the desired transformation for a range of 23 substrates proceeding in up to 99% yield.…”

“…In comparison to carbonyl–olefin ring-closing metathesis reactions resulting in 5-membered rings, the analogous transformations forming their higher-order homologues in the form of 6- or 7-membered ring products are much less developed. Successful, general reports for Lewis acid-catalyzed carbonyl–olefin ring-closing metathesis reactions currently center on polyaromatic hydrocarbons and tetrahydropyridines as products, while efficient strategies giving rise to functionalized cyclohexene products have only recently been reported. However, isolated early reports for Lewis acid-catalyzed carbonyl–olefin metathesis reactions for the synthesis of cyclohexenes do exist.…”

“…The Schindler group reported in 2020 the FeCl 3 -catalyzed formation of functionalized tetrahydropyridines 436 . Amino acids serve as chiral pool reagents to access N -containing aryl ketones 434 using a variety of electron-poor sulfonamide protecting groups (Scheme ).…”