Alexander Breder

Direct Oxidative Allylic and Vinylic Amination of Alkenes through Selenium Catalysis

Direct Oxidative Allylic and Vinylic Amination of Alkenes through Selenium Catalysis Bringing “N” into the game: The direct chemoselective nitrogenation of unactivated alkenes can be achieved through oxidative selenium catalysis (see scheme). This protocol provides a broad variety of allylic imides in yields of up to 89 % using N-fluorobenzenesulfonimide (NFSI) as the terminal oxidant and nitrogen source. Furthermore, an unprecedented selenium-catalyzed vinylic C(sp)–H nitrogenation was discovered. Angewandte Chemie

Selenium-Catalyzed Oxidative C(sp2)–H Amination of Alkenes Exemplified in the Expedient Synthesis of (Aza-)Indoles

A new selenium-catalyzed protocol for the direct, intramolecular amination of C(sp(2))-H bonds using N-fluorobenzenesulfonimide as the terminal oxidant is reported. This method enables the facile formation of a broad range of diversely functionalized indoles and azaindoles derived from easily accessible ortho-vinyl anilines and vinylated aminopyridines, respectively. The procedure exploits the pronounced carbophilicity of selenium electrophiles for the catalytic activation of alkenes and leads to the formation of C(sp(2))-N bonds in high yields and with excellent functional group tolerance.

Propargyl Alcohols as β-Oxocarbenoid Precursors for the Ruthenium-Catalyzed Cyclopropanation of Unactivated Olefins by Redox Isomerization

An atom-economical method for the direct synthesis of [3.1.0]- and [4.1.0]-bicyclic frameworks via Ru-catalyzed redox bicycloisomerization of enynols is reported. The presented results highlight the unique reactivity profile of propargyl alcohols, which function as β-oxocarbene precursors, in the presence of a ruthenium(II) complex. Furthermore, a rare case of a formal vinylic C-H insertion reaction is described.

Ugi-4-Component Reaction Enabling Rapid Access to the Core Fragment of Massadine

A rapid method to access the densely functionalized core structure of massadine (1) has been developed. The use of the Ugi-4-component reaction involving a convertible isonitrile and an end-group differentiating ozonolysis constitute the key operations toward the synthesis of the D-ring subunit.

Enantioselective Synthesis of the Carbocyclic D‐Ring Subunit of Massadine

functionalized, stereochemically rich alkaloids have made them veritable targets for synthesis studies. Herein we report an efficient asymmetric synthesis of the D-ring subunit embedded in massadine (1). Notable aspects of the strategy are: 1) the application of a cationic norbornyl rearrangement leading to facile functionalization, 2) an ozonolytic cleavage displaying remarkable end-group differentiation, and 3) a carboxy-inversion reaction for the installation of the requisite hindered secondary alcohol found in massadine (1). Collectively, these key transformations allow access to the fully functionalized carbocycle, which is a suitable launching point from which to address the challenges posed by the heterocycles in the natural product. The family of oroidin alkaloids, which includes axinellamines A (3) and B (4), palau amine (5), and massadine (1), presents a collection of synthetic hurdles such as the asymmetric construction of a densely functionalized, stereochemically intricate core, and its implementation in a synthetic route to assemble the heterocyclic array. Axinellamines A (3) and B (4) have succumbed to total synthesis, albeit in racemic form. Numerous efforts for the construction of the cyclopentane core, which is common to 2–5, have been documented (Figure 1 and Figure 2). 6] However, massadine (1) presents a unique challenge because it pos-

An Atom-Economical Access to β-Heteroarylated Ketones from Propargylic Alcohols via Tandem Ruthenium/Indium Catalysis

The direct and chemoselective synthesis of β-heteroarylated ketones from secondary propargyl alcohols through tandem Ru/In catalysis is reported. Both electron-rich and neutral heteroarenes, such as furans and indoles, efficiently undergo the redox isomerization/conjugate addition (RICA) sequence to provide the corresponding adducts in yields of up to 97%.

Selenium‐Catalyzed C(sp3)H Acyloxylation: Application in the Expedient Synthesis of Isobenzofuranones

Oxidative Se-catalyzed C(sp3)-H bond acyloxylation has been used to construct a diverse array of isobenzofuranones from simple ortho-allyl benzoic acid derivatives. The synthetic procedure employs mild reaction conditions and gives high chemoselectivity enabled by an inexpensive organodiselane catalyst. The presented approach offers a new synthetic pathway toward the core structures of phthalide natural products.

Towards the Synthesis of Massadine: A Unified Strategy for the Stereoselective Synthesis of the Carbocyclic C,D‐Ring Subunit

Massadine is a hexacyclic marine natural product, which belongs to the family of pyrrole-imidazole alkaloids. Herein, we describe a unified approach to the C,D-ring subunit of this sponge metabolite based on the exploitation of a norbornene scaffold for the stereocontrolled construction of massadines carbon skeleton. Highlights of the sequence presented include the application of a stereospecific norbornyl rearrangement for facile introduction of an oxygen at the C7-position within the norbornene nucleus, a highly regioselective and end group differentiating ozonolytic scission of a C-C double bond, and an oxidative decarboxylation reaction for the installation of the hindered secondary C2-alcohol function. Furthermore, the iterative assembly of the two guanidine entities as well as the implementation of the spirocyclic junction between the C- and the D-rings are described. Collectively, these key transformations permit an entry to an appropriately functionalized carbon framework, which will serve as a starting point for our efforts toward the completion of the synthesis of massadine.

Oxidative Allylic Esterification of Alkenes by Cooperative Selenium-Catalysis Using Air as the Sole Oxidant.

A new metal-free catalysis protocol for the oxidative coupling of nonactivated alkenes with simple carboxylic acids has been established. This method is predicated on the cooperative interaction of a diselane and a photoredox catalyst, which allows for the use of ambient air or pure O2 as the terminal oxidant. Under the title conditions, a range of both functionalized and nonfunctionalized alkenes can be readily converted into the corresponding allylic ester products with good yields (up to 89%) and excellent regioselectivity as well as good functional group tolerance.

Atom-economical synthesis of functionalized cycloalkanes via catalytic redox cycloisomerization of propargyl alcohols.

An atom-economical procedure for the direct synthesis of cycloalkanes from propargyl alcohols is reported. This high-yielding one-pot process involves a sequence consisting of a Ru-catalyzed redox isomerization of ynols into enones or an enal followed by an intramolecular Michael addition of a variety of carbon nucleophiles. Furthermore, an asymmetric variant of this protocol realized by the aid of a chiral nonracemic diamine catalyst, which provides the cyclization products in up to 97% ee, is presented.