Remote C–H Activation Strategy Enables Total Syntheses of Nortriterpenoids (±)-Walsucochin B and (±)-Walsucochinoids M and N

Abstract

Total syntheses of (±)-walsucochin B and (±)-walsucochinoids M and N have been achieved from farnesyl bromide. The key steps of the synthetic sequence are the titanocene-mediated radical cyclization and base-induced cycloaromatization for the rapid construction of the 6/6/5/6-fused tetracyclic skeleton. Importantly, a Cu-mediated remote C−H hydroxylation reaction has been developed to site-selectively install the oxygen function at the C-7 position of the target molecules, thus solving the biggest challenge for the synthesis of the compounds.Letter pubs.acs.org/OrgLett

Bidirectional Total Synthesis of Phainanoid A via Strategic Use of Ketones

“…Attempts with other types of polyene cyclization failed to provide the needed diastereoselectivity. A three-step functional group maneuver including carbonyl reduction, ozonolysis, and diol protection efficiently afforded ketone 13 , which served as an excellent substrate for the Baran’s modified Schönecker C–H oxidation to introduce the C7 alcohol ( 14 ) with consistent equatorial selectivity ,, in 76% yield. After methoxymethyl (MOM) protection of the C7 hydroxy group, the ring expansion of the cyclopentanone moiety was first realized in a three-step sequencediastereoselective vinyllithium addition (see the Supporting Information for preparation of the substrate), vanadium-catalyzed directed epoxidation, and AlMe 3 -mediated semipinacol rearrangementto provide cyclohexanone 18 .…”

Divergent Entry to Walsucochin Nortriterpenoids: Total Syntheses of (±)-Walsucochin A and (±)-Walsucochinoids C–F

“…Very recently, we reported a concise total synthesis of nortriterpenoids including (±)-walsucochin B (2) and (±)-walsucochinoids M and N (13,14) via the intermediate 22. 23 reaction to site-selectively install the oxygen function at the C-7 position of the target molecules (Scheme 1b). We were keen to extend the reach of this chemistry and in particular to establish its application to other walsucochin nortriterpenoids.…”

“…Our synthetic route started from the known product 22, which was prepared on a muti-gram scale in 8 steps for the syntheses of (±)-walsucochin B (2) and (±)-walsucochinoids M and N (13, 14) (Scheme 1b−c). 23 The iodide 23 was proposed to be the key intermediate, from which walsucochin A (1) and walsucochinoids C−F (3−6) could be approached through cross-coupling reactions. To realize the conversion of 22 to 23, because the benzylic position in compound 22 is sensitive to oxidation conditions, a selective oxidation reaction needs to be utilized to install the conjugated carbonyl moiety in the ring A.…”

“…Their synthesis relies on a cationic polyolefin cyclization to construct the core framework and the stereocenters in the natural product, a late-stage free-radical halogenation, and Seyferth–Gilbert homologation to install the acetylene moiety (Scheme a). Very recently, we reported a concise total synthesis of nortriterpenoids including (±)-walsucochin B ( 2 ) and (±)-walsucochinoids M and N ( 13 , 14 ) via the intermediate 22 . Key steps of our synthetic route are the radical cyclization and benzannulation for rapid construction of the 6/6/5/6-fused tetracyclic skeleton, a Cu-mediated C-H hydroxylation reaction to site-selectively install the oxygen function at the C-7 position of the target molecules (Scheme b).…”

“…Our synthetic route started from the known product 22 , which was prepared on a muti-gram scale in 8 steps for the syntheses of (±)-walsucochin B ( 2 ) and (±)-walsucochinoids M and N ( 13 , 14 ) (Scheme b–c) . The iodide 23 was proposed to be the key intermediate, from which walsucochin A ( 1 ) and walsucochinoids C–F ( 3 – 6 ) could be approached through cross-coupling reactions.…”