Angelw: through photochemical series reaction, the original ilurane framework was constructed concisely and the synthesis of atlantisone C was realized for the first time

Protoiludane (Figure 1, a) is a natural product skeleton of great concern, which exists in a variety of sesquiterpenes with biological activities, such as atlantisone C (1), Δ 6-protoiludene (2) and paesslerin a (3) The cyclohexane of the framework center is surrounded by the cyclobutane with the quaternary carbon center C3 and the cyclopentane with the amido dimethyl substitution at the C2 and C9 positions At present, researchers have developed many synthesis methods to construct the core structure of the original ilurane One of the methods is to construct a three ring skeleton from a non ring or single ring precursor via a biomimetic synthesis path The other method is to synthesize several ring structures in turn, especially the construction of cyclobutane Recently, Professor Thorsten Bach of Munich University of Technology reported the series reaction caused by the addition of neighboring photochemical rings, and synthesized the core structure of structure a in a single operation, namely the bicyclic [4.2.0] octane skeleton (J org Chem 2018, 83, 3069-3077) Inspired by this, recently, the research group developed a simple and efficient method for the synthesis of protoilurane sesquiterpenes For the first time, the total synthesis of atlantisone C (1) and the stereoselective synthesis of the key intermediates of Δ 6-protoilludene (2) and paesslerin a (3) were realized The related research results were published in angelw Chem Int ed (DOI: 10.1002/anie.201908619) (source: angelw Chem Int ed.) it is well known that aromatics B with carbonyl group in the ortho position of alkoxy group can form unstable product C by photocatalysis [2 + 2] cycloaddition, and cyclooctriene D can be formed by pair of ring opening CyclinE D is cyclized by continuous irreversible counter rotation [4 π], and the product e or e '(scheme 1) is generated according to the substitution mode of the chain system (source: angelw Chem Int ed.) through the continuous exploration of the substrate and conditions, the author found that under the visible light irradiation of γ ≥ 350 nm, ketone 6 can smoothly carry out the photochemical series reaction, and the target product indole ketone 7 (scheme 3) can be obtained in 60% yield (source: angelw Chem Int ed.) 7 is transformed into atlantisone C (1) by adjusting the oxidation state of several carbon atoms and introducing the stereocenter at C2 First, cyclobutane 7 is reduced and hydrogenated to form cyclobutane 8, then n-toluenesulphonylhydrazide condenses with ketone in 8 to form hydrazone 9, and then the product 11 is obtained by reduction In this process, the hydrogen in intermediate 10 migrates from the correct enantiomeric surface, and the C9 / C10 double bond is constructed in E11 The author treated EN11 with Schlosser lochmann base Buli / kotbu, then quenched it with BF (OME) 2 · OET 2, and then oxidized it to produce product 13 The deprotection process may be carried out by boric acid ester 12, which is oxidized and hydrolyzed to diol 13 and formic acid Diol 13 was oxidized to aldehydes by Swern, and then dehydrated to aldehydes 14 under the action of MscL, water and DMAP Next, ester 16 is obtained by reduction and acetyl protection C8 methylene in ester 16 is oxidized by pyridine and CrO 3 to obtain 17, and then saponified to form the required alcohol 1 (source: angelw Chem Int ed.) in order to demonstrate the practicability of the photochemical tandem reaction in the synthesis of proto iluransesquiterpenes, the authors prepared compounds 18 and 19, which are the precursors of paesslerin a (3) and δ 6-protoilludene (2), respectively Using diol 13 as the starting material, the product 18 was obtained by enantioselective hydrogenation, and the chiral center was constructed on C9 Alcohol 18 was oxidized to ketone 19 by DESs Martin in 60% yield (source: angelw Chem Int ed.) concluded that the author developed a simple route for the preparation of protoiluransesquiterpenoids from substituted indolones The photochemical series reaction established the correct structure of carbon ring framework and ensured its relative configuration The product 7 can be synthesized in 9 steps with 6% yield In addition, Δ 6-protoilludene and paesslerin a were prepared by using the key photochemical intermediates.