Enantioselective Total Synthesis of (+)‐Plumisclerin A

Abstract

The first and enantioselective total synthesis of (+)-plumisclerin A, a novel unique complex cytotoxic marine diterpenoid, has been accomplished. Around the central cyclopentane anchorage, a sequential ring-formation protocol was adopted to generate the characteristic tricycle[4.3.1.0 ]decane and trans-fused dihyrdopyran moiety. Scalable enantioselective La -catalyzed Michael reaction, palladium(0)-catalyzed carbonylation and SmI -mediated radical conjugate addition were successfully applied in the synthesis, affording multiple grams of the complex and rigid B/C/D-ring system having six continuous stereogenic centers and two all-carbon quaternary centers. The trans-fused dihyrdopyran moiety with an exo side-chain was furnished in final stage through sequential redox transformations from a lactone precursor, which overcome the largish steric strain of the dense multiring system. The reported total synthesis also confirms the absolute chemistries of natural (+)-plumisclerin A.

Recent advances in the total synthesis of cyclobutane-containing natural products

“…In 2018, Yao and co-workers reported the first total synthesis of (+)-plumisclerin A (26), which proceeded enantioselectively and thus allowed the determination of its absolute configuration (Scheme 4). 17 Their synthesis commenced with the asymmetric conjugate addition of malonate 21 to cyclopentenone 20 catalyzed by (S,S)-La-bis-BINOL 22 (10 mol%), providing 23 with 67% yield and >98% ee on a large scale. The following conversion of 23 to aldehyde 24 was realized in 18% overall yield over ten steps, setting the stage for the subsequent ketyl-olefin radical cyclization.…”

Total syntheses of strained polycyclic terpenes

“…The synthesis of this structurally interesting natural product was first reported 2018 by Yao and co-workers ( Scheme 8 ). 4 …”

Rhodium-catalyzed reductive carbonylation of aryl iodides to arylaldehydes with syngas

“…Rh salts generally play vital roles in the catalytic results. Therefore, we tested 20 different Rh salts and the results are summarized in low yield (Table 1, entries [17][18][19][20]. This strongly implied that not only the valence state of Rh and the species of anions were crucial for the conversion (even if all with halogen anions), but also structural differences (e.g., crystal water, RhCl 3 vs RhCl 3 ·3H 2 O) of analogous Rh salts played an important role in the catalytic synthesis of benzaldehyde.…”

“…In addition, relatively little attention has been paid to carbonylation chemistry using CO in academic research. Also, H 2 as representative clean energy source is far more environmentally friendly than other frequently used hydrogen sources like hydrosilanes [17], tributyltin hydride (Bu 3 SnH) (often used in natural product syntheses) [18][19][20] and hydroboranes [21][22][23], since the only byproduct is water. The production, storage and use of H 2 received much attention and plentiful achievements promoted the application of H 2 into more and more chemistry researches and industrial productions [24][25][26][27].…”