Interrupted Carbonyl‐Alkyne Metathesis

Carbonyl‐olefin metathesis and carbonyl‐alkyne metathesis represent established reactivity modes between carbonyls, alkenes, and alkynes under Lewis and Brønsted acid catalysis. Recently, an interrupted carbonyl‐olefin metathesis reaction has been reported that results in tetrahydrofluorenes via a distinct fragmentation of the reactive intermediate. We herein report the development of an analogous transformation interrupting the carbonyl‐alkyne metathesis reaction path resulting in dihydrofluorene products relying on Lewis acidic superelectrophiles as active catalytic species.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153682/1/adsc201901358.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153682/2/adsc201901358_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153682/3/adsc201901358-sup-0001-misc_information.pd

Charting a course for chemistry

To mark the occasion of Nature Chemistry turning 10 years old, we asked scientists working in different areas of chemistry to tell us what they thought the most exciting, interesting or challenging aspects related to the development of their main field of research will be — here is what they said

Visible Light-Enabled Paternò-Büchi Reaction via Triplet Energy Transfer for the Synthesis of Oxetanes

One of the most efficient ways to synthesize oxetanes is the light-enabled [2+2] cycloaddition reaction of carbonyls and alkenes, referred to as the Paternò-Büchi reaction. The reaction conditions for this transformation typically require the use of high energy UV light to excite the carbonyl, limiting the applications, safety, and scalability. We herein report the development of a visible light-mediated Paternò-Büchi reaction protocol that relies on triplet energy transfer from an iridium-based photocatalyst to the carbonyl substrates. This mode of activation is demonstrated for a variety of aryl glyoxylates and negates the need for both, visible light-absorbing carbonyl starting materials or UV light to enable access to a variety of functionalized oxetanes in up to 99% yield. <br /

Intramolecular, Visible Light-Mediated Aza Paternò-Büchi Reactions of Unactivated Alkenes

Azetidines are of particular interest in medicinal chemistry for their favorable properties, including increased resistance to oxidative metabolism and lower lipophilicity. The recent development of [2+2] reactions has significantly benefitted the previously limited methods for azetidine synthesis, but access to more complex architectures still requires further development. Herein we report a visible-light enabled intramolecular [2+2] cycloaddition to access tricyclic azetidines with 3D complex structures and high levels of saturation

Catalytic, Transannular Carbonyl-Olefin Metathesis Reactions

A new class of Lewis acid-catalyzed carbonyl-olefin metathesis reactions is described that complements existing protocols for related ring-closing, ring-opening, and intermolecular transformations. These transannular carbonyl-olefin metathesis reactions rely on FeCl3 as an inexpensive Lewis acid catalyst and are mechanistically distinct from previously developed protocols for ring closing, ring-opening and intermolecular metathesis. Specifically, carbonyl-ene and carbonyl-olefin metathesis reaction paths are competing to ultimately favor metathesis as the thermodynamic product. Importantly, we show that distinct Lewis acid catalysts are able to differentiate between these pathways to enable the selective formation of transannular carbonyl-ene or carbonyl-olefin metathesis products thus providing a valuable approach to the molecular editing of naturally occurring complex molecules. Additionally, these results are expected to enable further advances in catalyst design for carbonyl-olefin metathesis to ultimately develop efficient and high-yielding catalytic carbonyl olefination reactions

Bioinspired Syntheses of Herqulines B and C from Cyclodipeptide Mycocyclosin

A bioinspired approach for the syntheses of herqulines B and C is reported that takes advantage of an Ltyrosine-derived diketopiperazine, a mycocyclosin analog, as a synthetic precursor. The strategy relies on a series of consecutive reductions to adjust the mycocyclosin oxidation state to that observed in the herquline class of natural products. The strained and distorted L-tyrosine-based biaryl system characteristic for mycocyclosin is selectively converted to the 1,4-diketone structural motif common to the herqulines via initial hypervalent iodine-mediated dearomatization and a subsequent directed Birch reduction, enabled by an intramolecular H-source. The piperazine oxidation state is accessible in an iron-catalyzed reduction of the diketopiperazine precursor.</div

1- and 2-Azetines via Visible Light-Mediated [2+2]-Cycloadditions of Alkynes and Oximes

Azetines, four-membered unsaturated nitrogen-containing heterocycles, hold great potential for drug design and development, but remain underexplored due to challenges associated with their synthesis. We report an efficient, visible light-mediated approach to-wards 1- and 2-azetines relying on alkynes and the unique triplet state reactivity of oximes, specifically 2-isoxazolines. While 2-azetine products are accessible upon intermolecular [2+2]-cycloaddition via triplet energy transfer from a commercially available iridi-um photocatalyst, the selective formation of 1-azetines proceeds upon a second, consecutive, energy transfer process. Mechanistic studies are consistent with a stepwise reaction mechanism via N-O bond homolysis following the second energy transfer event to result in the formation of 1-azetine products. Characteristic for this method is its operational simplicity, mild conditions and modular approach that allows for the synthesis of functionalized azetines and tetrahydrofurans via in situ hydrolysis from readily available precursors