An asymmetric total synthesis of (-)-trans-blechnic acid, a dihydrobenzofuran neolignan, has been achieved. The key steps involve an elaboration of the cis-2,3-dihydrobenzofuran core structure by enantio-and diastereoselective intramolecular C-H insertion using dirhodium(II) tetrakis[N-phthaloyl-(R)-tert-leucinate] [Rh 2 (R-PTTL) 4 ] and a direct coupling of an acrylate unit with the core structure employing Yu's palladium(II)-catalyzed intermolecular C-H olefination.
Asymmetric Total Synthesis of (-)-trans-Blechnic Acid via Rhodium(II)-Catalyzed C-H Insertion and Palladium(II)-Catalyzed C-H OlefinationReactions. -(-)-trans-blechnic acid (I) has an uncommon 2,3-cis-stereochemistry and belongs to the dihydrobenzofuran neolignans, which exhibit several biological activities. The first asymmetric total synthesis of (I) is achieved in 15 steps and with an overall yield of 9%. The cis-2,3-dihydrobenzofuran core structure is formed by an enantio-and diastereoselective intramolecular C-H-insertion employing a chiral rhodium catalyst and an intermolecular C-H-olefination. -(ITO, M.; NAMIE, R.; KRISHNAMURTHI, J.; MIYAMAE, H.; TAKEDA, K.; NAMBU, H.; HASHIMOTO*, S.; Synlett 25 (2014) 2, 288-292, http://dx.
A highly diastereo-and enantioselective intramolecular 1,6-C-H insertion reaction of diaryldiazomethanes possessing an ether group has been achieved with the use of dirhodium(II) tetrakis[N-phthaloyl-(S)-tert-leucinate] as a catalyst, providing exclusively 3-substituted cis-3,4-dihydro-4-phenyl-1H-isochromans in up to 99% ee with no evidence of tandem ylide formation-rearrangement. Chiral dirhodium(II) complex-catalyzed intramolecular C-H insertion reaction of diazo compounds represents one of the most powerful methods for the construction of both optically active carbocycles and heterocycles, featuring C-C bond formation at an unactivated carbon atom with simultaneous creation of new stereogenic centers. 1-3 McKervey et al. were the first to demonstrate asymmetric induction (up to 12% ee) in intramolecular C-H insertion reactions when cyclization of α-diazo-β-ketosulfones was explored by devising dirhodium(II) tetrakis[N-benzenesulfonyl-(S)-prolinate], Rh 2 (S-BSP) 4 (1). 4 Significant progress was made by Doyle et al. in intramolecular C-H insertion reactions of α-diazoacetates and α-diazoacetamides by the development of chiral dirhodium(II) carboxamidates such as Rh 2 (5S-MEPY) 4 (2a), Rh 2 (4S-MEOX) 4 (2b), and Rh 2 (4S-MPPIM) 4 (2c). 5 In this area, we have developed chiral dirhodium(II) carboxylate complexes that incorporate N-phthaloyl-(S)-amino acids as † Dedicated to Professor Dr. Yasuyuki Kita on the occasion of his 77th birthday
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