Spatiotemporal Control of Pre-existing Alkene Geometry: A Bio-Inspired Route to 4-Trifluoromethyl-2H-chromenes

Abstract

Routes to prepare C4-trifluoromethyl analogues of the 2H-chromene scaffold are scarce: this is particularly striking given the importance of fluorine in pharmaceutical development. To address this limitation, a facile strategy has been developed that is reliant on catalytic, geometric isomerization of easily accessible allylic alcohols (up to >95:5) followed by intramolecular cyclization via Pd catalysis (up to 96%). This concise biomimetic approach emulates the photoisomerization/cyclization cascade inherent to phenylpropanoid biosynthesis.

Positional and Geometrical Isomerisation of Alkenes: The Pinnacle of Atom Economy

“…[71,73] These general reaction design principles are expansive and have been extended to enable the E!Z isomerisation of the corresponding allylic alcohols (Scheme 15). [74] Most recently, the geometric isomerisation of styrenyl boron species was reported. [75] Given the importance of boron nucleophiles in contemporary cross-coupling technologies,a ccess to these versatile 2D vectors was urgently required.…”

“…The ability of (−)‐riboflavin to undergo photo‐induced single electron transfer, in addition to being a competent photosensitiser, enabled a biomimetic “ one‐photocatalyst, n‐activation mode ” synthesis of coumarins starting from simple cinnamic acids (vide infra) . These general reaction design principles are expansive and have been extended to enable the E → Z isomerisation of the corresponding allylic alcohols (Scheme ) . Most recently, the geometric isomerisation of styrenyl boron species was reported .…”

Positionelle und geometrische Isomerisierung von Alkenen: der Gipfel der Atomökonomie

“…Eine Dichotomie von Singulett-und Tr iplett-Energietransfer sowie die Bedeutung von Alkenpolarisierung und allylischer Spannung fürh ohe Selektivität( Z/E bis zu 99:1) wurden herausgestellt. [74] Erst kürzlich wurde über die geometrische Isomerisierung von Styrol-Bor-Spezies berichtet. [71,73] Diese generellen Reaktionsdesignprinzipien sind umfangreich und wurden ausgeweitet, um die E!Z-Isomerisierung der entsprechenden Allylalkohole zu ermçglichen (Schema 15).…”

“…[71,73] Diese generellen Reaktionsdesignprinzipien sind umfangreich und wurden ausgeweitet, um die E!Z-Isomerisierung der entsprechenden Allylalkohole zu ermçglichen (Schema 15). [74] Erst kürzlich wurde über die geometrische Isomerisierung von Styrol-Bor-Spezies berichtet. [75] Wegen der großen Bedeutung von Bornukleophilen in Kreuzkupplungstechniken war ein Zugang zu diesen vielfältigen zweidimensionalen Vektoren dringend nçtig.D ie Anwendung in der Synthese von Combretastatin A-4 unterstreicht dabei den Nutzen von kontra-thermodynamischen Isomerisierungen im Repertoire der Synthesechemie.…”

Energy-Transfer-Mediated Photocatalysis by a Bioinspired Organic Perylenephotosensitizer HiBRCP

“…Photochemistry, 1 simulating the natural photosynthesis to use sunlight to drive multifarious chemical transformations, is of great practical significance for the development of sustainable energy. Among them, energy-transfer (EnT) photocatalysis 2 has emerged as a gentle and selective approach to access highly reactive triplet states through indirect excitation and achieved a series of special transformations, such as cycloadditions, 3 rearrangements, 4 fragmentations, 5 especially geometrical isomerization of alkenes, 6 and sensitization of organometallic intermediates. 7 In this process, a photosensitizer (PS) with excellent photostability, powerful absorption, and higher energy of the triplet state than the substrate is the basis for realizing more extensive applications in drug synthesis and the chemical industry.…”