Asymmetric Total Synthesis of (–)-trans-Blechnic Acid via Rhodium(II)-Catalyzed C–H Insertion and Palladium(II)-Catalyzed C–H Olefination Reactions

Abstract

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.

Transition Metal‐Catalyzed Enantioselective Synthesis of Chiral Five‐ and Six‐Membered Benzo O‐heterocycles

“…Meanwhile, Hashimoto research group achieved insertion into benzylic C−H bonds with excellent cis selectivity and good ee s using Rh 2 (S‐PTTL) 4 TMC31 , which developed by their group, as could catalyze reactions in short time [213] . Application of this catalyst to synthesis of (−)‐ trans ‐blechnic acid also reported by the authors [214] . This method also used in total synthesis of aperidine by Wakimoto and co‐workers [215] .…”

“…[213] Application of this catalyst to synthesis of (À )-trans-blechnic acid also reported by the authors. [214] This method also used in total synthesis of aperidine by Wakimoto and co-workers. [215] Further, modification of the catalyst to give triethylmethyl substituted Rh complex TMC32 and its utilization to synthesis of (À )-epiconocarpan and (+)-conocarpan was also successful.…”

Catalytic asymmetric carbenoid α-C–H insertion of ether

“…This motif was exploited in their following work on the asymmetric total synthesis of (−)- trans -blechnic acid, wherein they modified the rhodium catalyzed insertion reaction reported earlier ( Scheme 3a ). 17 Additionally, aliphatic substrates were tested, yielding excellent diastereoselectivity, high yields and moderate enantioselectivity under standard reaction conditions (6k).…”