Among all metathesis reactions known to date in organic chemistry, the metathesis of multiple bonds such as alkenes and alkynes has evolved into one of the most powerful methods to construct molecular complexity. In contrast, metathesis reactions involving single bonds are scarce and far less developed, particularly in the context of synthetically valuable ring-closing reactions. Herein, we report an iron-catalyzed ring-closing metathesis of aliphatic ethers for the synthesis of substituted tetrahydropyrans and tetrahydrofurans, as well as morpholines and polycyclic ethers. This transformation is enabled by a simple iron catalyst and likely proceeds via cyclic oxonium intermediates.

Unprotected, primary 2-azidoamines are versatile precursors to vicinal diamines, which are among the most common motifs in biologically active compounds. Herein, we report their operationally simple synthesis through an iron-catalyzed difunctionalization of alkenes. A wide array of alkene substrates are tolerated, including complex drug-like molecules and a tripeptide. Facile derivatizations of the azidoamine group demonstrate the versatility of this masked diamine motif in chemoselective, orthogonal transformations. Applications of the methodology in the concise synthesis of RO 20-1724 and in a formal total synthesis of (±)-hamacanthin B further demonstrate the broad synthetic potential of this highly functional group tolerant reaction.Vicinal diamines are privileged structural motifs encountered across the molecular sciences, particularly in natural products, medicinal chemistry and catalysis. 1 Therefore, the rapid access to this ubiquitous functionality starting from simple hydrocarbon feedstocks, such as alkenes, can dramatically facilitate the synthesis and discovery of functional molecules. Several approaches have been explored to install two vicinal amino groups through the catalytic diamination of alkenes. 2 However, these reactions are still considerably limited when compared to well established methods for the synthesis of other important 1,2-difunctionalized alkanes, such as diols. 3 Besides the scope being often limited to activated alkenes, a more significant limitation is the lack of methods to access a diamine precursor which can be orthogonally transformed into synthetically relevant unsymmetrical diamine products (Scheme 1). Scheme 1. Importance of unsymmetrical vicinal diaminesThe azido group has recently emerged as a convenient amino group surrogate in formal catalytic diamination reactions (Scheme 2). 4 Most notably, Lin 5 and Xu 6 have described elegant electrochemical and iron-catalyzed processes, respectively, for the direct synthesis of diazides starting from a wide variety of alkenes (Scheme 2a). Whereas these reactions are powerful tools to access symmetrical vicinal diamines in two steps, they are less suitable in cases where two chemically distinct amino groups need to be orthogonally synthesized (e. g. through amide coupling), a scenario which is common in target-oriented synthesis. 7 Indeed, diazides suffer from poor regioselectivity upon monoreduction, making the direct synthesis of 2-azidoamines from alkenes highly challenging. 8 catalyzed the desired reaction in good yields using this usually unreactive substrate (Entries 1, 3, 4). The possible catalytic effect of impurities from the iron source was ruled out by a control experiment with a trace metals-based source which Scheme 3. Scope of the aminoazidation reaction Yields are of isolated products; dr determined by 1 H-NMR. a (E)-alkene used. b Purified via column chromatography. c Purified via ammonium salt precipitation. d Starting from an ester bearing a terminal alkene. e See SI for detailed experimental information.

We report herein the asymmetric coupling of flow‐generated unstabilized diazo compounds and propargylated amine derivatives, using a new pyridinebis(imidazoline) ligand, a copper catalyst and base. The reaction proceeds rapidly, generating chiral allenes in 10–20 minutes with high enantioselectivity (89–98 % de/ee), moderate yields and a wide functional group tolerance.

Secondary and tertiary alkylamines are privileged substance classes that are often found in pharmaceuticals and other biologically active small molecules. Herein, we report their direct synthesis from alkenes through an aminative difunctionalization reaction enabled by iron catalysis. A family of ten novel hydroxylamine‐derived aminating reagents were designed for the installation of several medicinally relevant amine groups, such as methylamine, morpholine and piperazine, through the aminochlorination of alkenes. The method has excellent functional group tolerance and a broad scope of alkenes was converted to the corresponding products, including several drug‐like molecules. Besides aminochlorination, the installation of other functionalities through aminoazidation, aminohydroxylation and even intramolecular carboamination reactions, was demonstrated, further highlighting the broad potential of these new reagents for the discovery of novel amination reactions.

Electrophilic aminating reagents have seen a renaissance in recent years as effective nitrogen sources for the synthesis of unprotected amino functionalities.