We report the use of a strongly electrophilic thiyl radical derived from commercially available pentafluorothiophenol as a demonstration of highly chemoselective H atom abstraction from electron-rich and relatively weak benzylic C-H bonds adjacent to the O and N atoms. This approach enables the selective oxidative removal of benzyl and -methoxybenzyl groups from amines and ethers under ambient aerobic conditions.
View Article and Find Full Text PDFOrg Biomol Chem
October 2021
The importance and prevalance of O-, N-, and S-atom containing saturated four-membered ring motifs in biologically active molecules and potential therapeutics continues to drive efforts in their efficient synthetic preparation. In this review, general and recent strategies for the synthesis of these heterocycles are presented. Due to the limited potential bond disconnections, retrosynthetic strategies are broadly limited to cyclizations and cycloadditions.
View Article and Find Full Text PDFWe report herein the development of a S atom transfer process using triethyl phosphite as the S atom acceptor that allows thiols to serve as precursors of C-centered radicals. A range of functionalized and electronically unbiased alkenes including those containing common heteroatom-based functional groups readily participate in this reductive coupling. This process is driven by the exchange of relatively weak S-H and C-S bonds of aliphatic thiols for C-H, C-C, and S-P bonds of the products formed.
View Article and Find Full Text PDFPhenolic, lignin-derived substrates have emerged as desirable biorenewable chemical feedstocks for coupling reactions. A radical-mediated conversion of phenol derivatives to anilines is reported, using unfunctionalized hydroxamic acids as the N-centered radical source. The applicability of this triethyl phosphite mediated O-atom transfer approach, which tolerates a range of steric and electronic demands to naturally occurring phenols and lignin models, has been demonstrated in this work to access the corresponding aniline derivatives.
View Article and Find Full Text PDFPhotocycloadditions are often typified by the oxetane-forming Paternò-Büchi reaction. However, the mechanistic constraints of carbonyl excitation and olefin interception have limited this attractive oxetane-forming pathway. Here we describe the use of a Cu(I) precatalyst that achieves selective olefin activation via coordination to the metal center.
View Article and Find Full Text PDFAn intermolecular anti-Markovnikov hydroamination of alkenes has been developed using triethyl phosphite and N-hydroxyphthalimide. The process tolerates a wide range of alkenes, including vinyl ethers, silanes, and sulfides as well as electronically unbiased terminal and internal alkenes. The resultant N-alkylphthalimides can readily be transformed to the corresponding primary amines.
View Article and Find Full Text PDFThe selective, intermolecular [1,4]-hydrovinylation of conjugated dienes with unactivated α-olefins catalyzed by α-diimine iron complexes is described. Value-added "skipped" diene products were obtained with exclusive [1,4]-selectivity, and the formation of branched, ( Z)-olefin products was observed with no evidence for alkene isomerization. Mechanistic studies conducted with the well-defined, single-component iron precatalyst (DI)Fe(COD) (DI = [2,4,6-Me-CH-N═CMe]); COD = 1,5-cyclooctadiene) provided insights into the origin of the high selectivity.
View Article and Find Full Text PDFCycloadditions, such as the [4+2] Diels-Alder reaction to form six-membered rings, are among the most powerful and widely used methods in synthetic chemistry. The analogous [2+2] alkene cycloaddition to synthesize cyclobutanes is kinetically accessible by photochemical methods, but the substrate scope and functional group tolerance are limited. Here, we report iron-catalyzed intermolecular [2+2] cycloaddition of unactivated alkenes and cross cycloaddition of alkenes and dienes as regio- and stereoselective routes to cyclobutanes.
View Article and Find Full Text PDFAryl-substituted bis(imino)pyridine cobalt dinitrogen compounds, ((R)PDI)CoN2, are effective precatalysts for the intramolecular [2π + 2π] cycloaddition of α,ω-dienes to yield the corresponding bicyclo[3.2.0]heptane derivatives.
View Article and Find Full Text PDFTransformations that selectively functionalize aliphatic C-H bonds hold significant promise to streamline complex molecule synthesis. Despite the potential for site-selective C-H functionalization, few intermolecular processes of preparative value exist. Herein, we report an approach to unactivated, aliphatic C-H bromination using readily available N-bromoamide reagents and visible light.
View Article and Find Full Text PDFThe dioxygenation of alkenes using molecular oxygen and a simple hydroxamic acid derivative has been achieved. The reaction system consists of readily prepared methyl N-hydroxy-N-phenylcarbamate and molecular oxygen with a radical initiator, offering an alternative to common dioxygenation processes catalyzed by precious transition metals. This transformation capitalizes on the unique reactivity profile of hydroxamic acid derivatives in radical-mediated alkene addition processes.
View Article and Find Full Text PDFA radical-mediated approach to metal-free alkene oxyamination is described. This method capitalizes on the unique reactivity of the amidoxyl radical in alkene additions to furnish a general difunctionalization using simple diisopropyl azodicarboxylate (DIAD) as a radical trap. This protocol capitalizes on the intramolecular nature of the process, providing single regioisomers in all cases.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
June 2010