Enantioselective Total Synthesis of (+)‐Steenkrotin A and Determination of Its Absolute Configuration

Abstract

The first enantioselective total synthesis of (+)-steenkrotin A has been achieved in 18 steps and 4.2 % overall yield. The key features of the strategy entail a Rh-catalyzed O-H bond insertion followed by an intramolecular carbonyl-ene reaction, two sequential SmI2 -mediated Ueno-Stork and ketyl-olefin cyclizations, and a cascade intramolecular aldol condensation/vinylogous retro-aldol/aldol process with inversion of the relative configuration at the C7 position. The absolute configuration of (+)-steenkrotin A was determined based on the stepwise construction of the stereocenters during the total synthesis.

Total Synthesis of (+)-Aplykurodinone-1

“…After extensive optimization, it was found that, to our delight, when a small amount of water was added to the reaction mixture, aldehyde 5 was obtained as the major product (83%), which, when heated in toluene at 160 °C for 17 h in a sealed tube, provided the desired cyclization product 6 in 90% yield (Scheme ). Other Lewis acids (Me 2 AlCl, Et 2 AlCl, SnCl 4 , Sc­(OTf) 3 ) also induced the carbonyl–ene cyclization but in moderate yields, along with the formation of considerable amounts of epimer 6a . Stereoselective epoxidation of 6 using a catalytic amount of VO­(acac) 2 afforded epoxide 7 (92%) with complete diastereocontrol.…”

Recent advances in the chemistry of ketyl radicals

“…The 2016 enantioselective total synthesis of (+)-steenkrotin ( 205 ) A by Ding et al provides a striking illustration of the differences in behaviour of tin and samarium ketyl radicals ( Scheme 29 ). 51 The synthetic plan relied on a ketyl–olefin cyclisation of aldehyde 198 to build the tetracyclic core of the natural product 199 . Rather than delivering 199 , treatment of 198 with n -Bu 3 SnH in refluxing benzene gave undesired, rearrangement product 200 in 63% yield.…”

Diastereoselective Synthesis of the Hydroperoxide–Keto Form of (±)-Steenkrotin B

“…The unique architectures, potentially important bioactivities, and interesting biogenetic pathways of steenkrotins A and B have prompted us to launch their chemical synthesis. Very recently, we achieved the first asymmetric total synthesis of steenkrotin A in a concise and efficient manner based on a cascade intramolecular aldol/vinylogous retro-aldol/aldol process . Herein, we report a diastereoselective total synthesis of the claimed structure of steenkrotin B in its hydroperoxide–keto form, which calls into question the assigned structure.…”