Search

Aziridines-three-membered nitrogen-containing cyclic molecules-are important synthetic targets. Their substantial ring strain and resultant proclivity towards ring-opening reactions makes them versatile precursors of diverse amine products 1-3 , and, in some cases, the aziridine functional group itself imbues important biological (for example, anti-tumour) activity 4-6 . Transformation of ubiquitous alkenes into aziridines is an attractive synthetic strategy, but is typically accomplished using electrophilic nitrogen sources rather than widely available amine nucleophiles. Here we show that unactivated alkenes can be electrochemically transformed into a metastable, dicationic intermediate that undergoes aziridination with primary amines under basic conditions. This new approach expands the scope of readily accessible N-alkyl aziridine products relative to those obtained through existing state-of-the-art methods. A key strategic advantage of this approach is that oxidative alkene activation is decoupled from the aziridination step, enabling a wide range of commercially available but oxidatively sensitive 7 amines to act as coupling partners for this strain-inducing transformation. More broadly, our work lays the foundations for a diverse array of difunctionalization reactions using this dication pool approach., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Carbohydrates are synthetically challenging molecules with vital biological roles in all living systems. Selective synthesis and functionalization of carbohydrates provide tremendous opportunities to improve our understanding on the biological functions of this fundamentally important class of molecules. However, selective functionalization of seemingly identical hydroxyl groups in carbohydrates remains a long-standing challenge in chemical synthesis. We herein describe a practical and predictable method for the site-selective and stereoselective alkylation of carbohydrate hydroxyl groups via Rh(II)-catalyzed insertion of metal carbenoid intermediates. This represents one of the mildest alkylation methods for the systematic modification of carbohydrates. Density functional theory (DFT) calculations suggest that the site selectivity is determined in the Rh(II)-carbenoid insertion step, which prefers insertion into hydroxyl groups with an adjacent axial substituent. The subsequent intramolecular enolate protonation determines the unexpected high stereoselectivity. The most prevalent trans- 1,2-diols in various pyranoses can be systematically and predictably differentiated based on the model derived from DFT calculations. We also demonstrated that the selective O -alkylation method could significantly improve the efficiency and stereoselectivity of glycosylation reactions. The alkyl groups introduced to carbohydrates by OH insertion reaction can serve as functional groups, protecting groups, and directing groups.

The first rhodium-catalyzed intramolecular [5 + 2] cycloaddition of 3-acyloxy 1,4-enyne and alkene was developed. The cycloaddition is highly diastereoselective in most cases. Various cis-fused bicyclo[5.3.0]decadienes were prepared stereoselectively. The chirality in the propargylic ester starting materials could be transferred to the bicyclic products with high efficiency. Electron-deficient phosphine ligand greatly facilitated the cycloaddition. Up to three new stereogenic centers could be generated. The resulting diene in the products could be hydrolyzed to enones, which allowed the introduction of more functional groups to the seven-membered ring.

Halocyclization of alkenes was realized using N-acylhemiaminal nucleophiles. High diastereoselectivity could be achieved for the formation of three stereogenic centers in this halogen-mediated cyclization reaction. We also demonstrated that enantioselective bromocyclization of alkenes using N-acylhemiaminal nucleophiles was possible., (© 2013 Wiley Periodicals, Inc.)

Rh(I) carbenes were conveniently generated from readily available ynamides. These metal carbene intermediates could undergo metathesis with electron-rich or neutral alkynes to afford 2-oxopyrrolidines or be trapped by tethered alkenes to yield 3-azabicyclo[3.1.0]hexanes, a common skeleton in numerous bioactive pharmaceuticals. Although the scope of the former is limited, the latter reaction tolerates various substituted alkenes.

Nitrogen-containing stereotriads, compounds with three adjacent stereodefined carbons, are commonly found in biologically important molecules. However, the preparation of molecules bearing these motifs can be challenging. Herein, we describe a modular oxidation protocol which converts a substituted allene to a triply functionalized amine of the form C-X/C-N/C-Y. The key step employs a Rh-catalyzed intramolecular conversion of the allene to a strained bicyclic methylene aziridine. This reactive intermediate is further elaborated to the target products, often in one reaction vessel and with effective transfer of the axial chirality of the allene to point chirality in the stereotriad.

We have discovered that the oxaziridine-mediated copper-catalyzed aminohydroxylation reaction recently discovered in our laboratories is dramatically accelerated in the presence of halide additives. The use of this more active catalyst system enables the efficient aminohydroxylation of electronically and sterically deactivated styrenes and also enables the use of nonstereogenic 3,3-dialkyl oxaziridines as terminal oxidants in the aminohydroxylation reaction. We present evidence that anionic halocuprate(II) complexes are the catalytically active species responsible for the increased reactivity under these conditions. This unexpected observation has led us to re-evaluate our mechanistic understanding of this reaction. On the basis of the results of a variety of radical trapping experiments, we propose a modified mechanism that involves a homolytic reaction of the olefin with a copper(II)-activated oxaziridine. Together, the observation that anionic additives significantly increase the oxidizing ability of oxaziridines and the recognition of the radical nature of reactions of oxaziridines under these conditions suggest that a variety of new oxidative transformations catalyzed by halocuprate(II) complexes should be possible.

[reaction: see text] Palladium(II) complexes bearing a single N-heterocyclic carbene ligand serve as effective catalysts for the aerobic oxidative cyclization of alkenes with pendant sulfonamides. The use of carboxylic acid cocatalysts (AcOH and PhCO(2)H) often leads to significant improvements in catalyst stability and product yield and enables catalytic turnover to be achieved with air, rather than pure oxygen gas, as the source of O(2).

A novel and efficient method for the synthesis of selenophenes is disclosed. Selenophenes were synthesized in high yields in a single operation from 1,3-dienes containing a carbonyl group at the C-1 position and selenium dioxide. The bidirectional synthesis of selenophenes can also be demonstrated using this method. The selenophene is believed to form via a [4 + 2] cycloaddition between diene and selenium dioxide.