The Enantioselective Synthesis of Eburnamonine, Eucophylline, and 16′‐epi‐Leucophyllidine

Abstract

Supporting information for this article is given via a link at the end of the document.

The Enantioselective Synthesis of Eburnamonine, Eucophylline, and 16′‐epi‐Leucophyllidine

“…36 Acetal cleavage then unmasks the aldehyde, which is homologated with a Peterson olefination. 37 At this point, we obtained X-ray quality crystals of 40 and we were dismayed to find that the reduction had occurred with the undesired stereochemistry to provide 16'-epi-leucophyllidine. Despite this unexpected result, we remained optimistic that the desired stereochemistry could be installed.…”

Total Synthesis of Strempeliopidine and Non-Natural Stereoisomers through a Convergent Petasis Borono–Mannich Reaction

“…49 Applying our previously developed asymmetric decarboxylative alkylation technology, we could access decagrams of enantioenriched lactam (−)-10 in 87% yield and 96% ee using 1.5 mol % of Pd(OAc) 2 and (R)-(CF 3 ) 3 -t-BuPHOX. 29 Using chemistry previously developed in our laboratory, lactam (−)-10 could be converted to iminium salt (−)-20, which we identified as a suitable precursor for both (−)-epi-eburnamonine ((−)-21) and (+)-eburnamonine ((+)-22). Following a procedure outlined by Wenkert, we were able to form the eastern pentacyclic ring system ((−)-21) by treatment of iminium (−)-20 with KOAc.…”

“…To synthesize the requisite eburnamonine vinyl triflate 9, a key Bischler−Napieralski reaction would be employed following trans-selective hydrogenation to afford the trans-20′β, 21′α-ring fusion. 29 Lactam (−)-10 would be derived from δ-valerolactam (11) using our lab's previously established scalable route exploiting a palladium-catalyzed asymmetric decarboxylative alkylation. 49 To access the western fragment 12, we would apply a hydroamination/Pictet−Spengler sequence to build up the pentacyclic framework of dehydro-aspidospermidine derivative (12) from acyl indole 13.…”

Recent Advances in the Construction of Quaternary Stereocenters via Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation

“…In 2021, the Stoltz group disclosed another synthetic approach to the heterodimeric bisindole alkaloid 16′-epileucophyllidine with Pd-catalyzed DAAA as the key step (Scheme 31). 69 The intermediate S1, bearing an all-carbon stereocenter, was generated with (R)-CF 3 -t-BuPHOX L17 as chiral ligand in 91% yield and 92% ee. Moreover, this key intermediate was synthesized on 14 g scale and could be further transformed into eburnamonine and eucophylline in 6 steps and 12 steps, respectively.…”