Browsing by Person "Khoshbakhsh Foumani, Mehran"

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Development of new methods for the transition metal-catalyzed synthesis of annulated pyrans
(2025) Khoshbakhsh Foumani, Mehran; Beifuss, Uwe
Annulated 4H-pyrans as well as fused 2H-pyran-2-ones are interesting synthetic targets, but the available methods for their preparation are limited. The aim of this work was to develop new transition metal-catalyzed reactions for the efficient and selective construction of annulated and bisannulated partially saturated pyrans and pyranones. In particular, 1,3-biselectrophiles should be used as substrates. The first part of the work is devoted to the development of a new access to 4H-pyrans 126 and 127 by reacting cyclic 1-bromoallyl tosylates 125 with 1,3-dicarbonyls. Optimization of a model reaction revealed that the highest yields were obtained when the two substrates were reacted with 10 mol% CuI, 2.2 equiv. Cs2CO3, and 10 mol% 2-picolinic acid in the presence of molecular sieve (4 Å) in DMF at 80 °C for 2 h. Reaction of 125 with cyclic 1,3-dicarbonyls 35, 104 allowed the synthesis of bisannulated 4H-pyrans 126 in yields up to 92% (Scheme 47). The significance of this method is that it provides access to five different heterocyclic scaffolds. The new domino reaction is not limited to cyclic 1,3-dicarbonyls 35, 104 as substrates. Six- membered 1-bromoallyl tosylates 125 could be successfully reacted with acyclic β-ketoesters 46 to give the 5,6,7,8-tetrahydro-4H-chromene-3-carboxylates 127 in yields up to 59% (Scheme 47). The high efficiency coupled with great flexibility and easy feasibility make this new method a valuable tool for synthesis. The annulation is assumed to be a domino reaction consisting of an intermolecular C-allylation followed by a Cu(I)-catalyzed intramolecular Ullmann-type O-vinylation. In the second part of the work, a novel regioselective method for the efficient synthesis of annulated 2H-pyran-2-ones was developed. The initial goal was a new approach to 7,8,9,10- tetrahydro-6H-benzo[c]chromenes 130 based on a transition metal-catalyzed intramolecular aromatic C−H alkenylation of 2-halo-1-(aryloxymethyl)cycloalk-1-enes 128, which are readily accessible from 1-bromoallyl tosylates 125. Although the desired cyclization of 128a to 130a was achieved, the product 130a could not be obtained in analytically pure form (Scheme 48). Therefore, the Ru-catalyzed intramolecular aromatic C−H alkenylation was combined with an allylic oxidation to form a new domino reaction for the synthesis of annulated 2H-pyran-2-ones 137 and 138. Optimization of the reaction conditions using a model reaction as an example showed that the highest yield was obtained when the first step was carried out with RuCl2(PPh3)3 as catalyst and 1,5-pentanediol as additive in DMA at 100 °C for 18 h and an excess of DTBP was used for the second step. Then, scope and limitations of the method was investigated. Under the optimized reaction conditions, it was possible to synthesize a series of 3,4-annulated coumarins 137 with yields up to 83% by reacting 2-bromo-1- (aryloxymethyl)cycloalk-1-enes 128 (Scheme 49). The high selectivity of the cyclization is remarkable. In substrates derived from phenol, resorcinol, and pyrogallol, ring closure occurs only at the C atom that is in ortho-position to the ether bridge and in para-position to the OH group of the substrate. It has also been demonstrated that the Ru-catalyzed intramolecular aromatic C−H alkenylation/allylic oxidation of allyl-α-(tetrahydro)naphthyl ethers 129 allows the regioselective synthesis of annulated naphthopyranones 138 with yields up to 90% (Scheme 50).