A new approach to the 8b-azaacenaphthylene ring system

Kamath, Anushree; Fabritius, Charles-Henry; Philouze, Christian; Delair, Philippe

doi:10.1039/c5ob01013f

Cited by 10 publications

(10 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accordingly, lactam had first to be partially reduced to an iminium ion that was then prone to undergo the cyclization. Classical reducing agents such as LiAlH 4 , Red-Al, or DIBAL-H resulted in a mixture of the recovered starting material and over-reduction to completely saturated amine. Moreover, combinations of the well-established activating agent Tf 2 O/2-fluoro pyridine with various reducing agents did not improve the results.…”

Section: Resultsmentioning

confidence: 99%

Short Synthesis of Alkaloid (−)-205B

Tripathy

Schneider

2020

J. Org. Chem.

View full text Add to dashboard Cite

The alkaloid (−)-205B has in the past served as a testing ground for novel approaches in nitrogen heterocycle synthesis. We herein report a highly straightforward synthesis of (−)-205B in just six synthetic steps, making it the shortest route currently known. The central steps of our approach are a vinylogous Mukaiyama–Mannich reaction to establish the first two stereogenic centers with excellent diastereo- and enantiocontrol followed by zinc-mediated Barbier allylation to set the third chiral center with high substrate control. Upon cyclization of the Barbier product to lactam and enolate methylation, the third ring is annulated by a one-pot sequence of lactam reduction and aza-Prins cyclization to directly set the final stereogenic center with complete cis-stereoselectivity. As the iminium ion undergoing the aza-Prins cyclization rapidly isomerized to a planar enamine intermediate, the alkaloid was eventually obtained as a 1:1 mixture of C6 diastereomers, which were readily separated by chromatography. Yet, the target natural product was obtained isomerically pure in an overall yield of 12%, which compares favorably with all previous syntheses.

show abstract

Section: Resultsmentioning

confidence: 99%

Short Synthesis of Alkaloid (−)-205B

Tripathy

Schneider

2020

J. Org. Chem.

View full text Add to dashboard Cite

show abstract

“…A poorly selective diazomethane ring expansion of a cyclobutanone observed many years ago has led to the discovery of effective approaches to a variety of cyclobutane, cyclopentane, γ-butyrolactone, and γ-butyrolactam-derived natural products, with attendant development of considerable new chemistry. Recently, in an extension of the above work, the 8 b -azaacenaphthylene tricyclic scaffold common to the dimeric ladybird alkaloids has been prepared . It is probable that this rich dichlorocyclobutanone-centered research will evolve yet further to provide novel solutions to other problems in organic synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, in an extension of the above work, the 8b-azaacenaphthylene tricyclic scaffold common to the dimeric ladybird alkaloids has been prepared. 51 It is probable that this rich dichlorocyclobutanone-centered research will evolve yet further to provide novel solutions to other problems in organic synthesis.…”

Section: ■ Concluding Remarksmentioning

confidence: 99%

Diverse Natural Products from Dichlorocyclobutanones: An Evolutionary Tale

et al. 2016

Self Cite

View full text Add to dashboard Cite

11-Nor PGE2 was prepared in our laboratory several years ago and used to obtain the corresponding ring-expanded γ-butyrolactam, γ-butyrolactone, and cyclopentanone derivatives. The conversion of a cyclobutanone into a cyclopentanone had relatively little precedent and merited further study. It was soon found that the presence of a single chlorine adjacent to the carbonyl not only greatly accelerated the reaction with ethereal diazomethane, but also substantially enhanced its regioselectivity; not surprisingly, a second chlorine further increased both. The confluence of this finding and the discovery by Krepski and Hassner that the presence of phosphorus oxychloride significantly improved the Zn-mediated dehalogenation procedure for the preparation of α,α-dichlorocyclobutanones from olefins provided the starting point for decades' worth of exciting adventures in natural product synthesis. A wide variety of naturally occurring 5-membered carbocycles (e.g., hirsutanes, cuparenones, bakkanes, guaianolides, azulenes) could thus be prepared by using dichloroketene-olefin cycloaddition, followed by regioselective one-carbon ring expansion with diazomethane. Importantly, it was also found that natural γ-butyrolactones (e.g., β-oxygenated γ-butyrolactones, lactone fatty acids) could be secured through regioselective Baeyer-Villiger oxidation of cycloadducts with m-CPBA and that naturally occurring γ-butyrolactam derivatives (e.g., amino acids, pyrrolidines, pyrrolizidines, indolizidines) could be efficiently obtained by regioselective Beckmann ring expansion of the adducts with O-(mesitylenesulfonyl)hydroxylamine (Tamura's reagent). These 5-membered carbocycles, γ-butyrolactones, and γ-butyrolactam derivatives were generally secured in enantiopure form through the use of either intrinsically chiral olefins or olefins bearing Stericol, a highly effective chiral auxiliary developed specifically for this "three-atom olefin annelation" approach. In addition, considerable useful chemistry has been developed in the context of this synthesis program. This includes new methods for olefin vicinal dicarboxylation, β-methylene-γ-butyrolactonization, γ-butyrolactone and δ-valerolactone α-methylenations, transesterification, angelic ester synthesis, chiral enol and ynol ether preparations, dichloroacetylene synthesis, and trans, trans hydroxy triad introduction. This versatile dichlorocyclobutanone-centered approach to natural product synthesis, together with the attendant new methods that have been developed, forms the basis of this Account, which is presented as an evolutionary tale. It is hoped that the Account will stimulate other research groups to seek to exploit the rich chemistry of dichlorocyclobutanones for possible solutions to problems in organic synthesis.

show abstract

“…In their efforts directed towards the synthesis of alkaloid (–)‐205B ( 165 ), extracted as traces from frog skin, Delair and co‐workers reported a new stereoselective approach to the 8b‐azaacenaphthylene core through a domino partial reduction/aza‐Prins cyclization sequence . The authors prepared lactam 166 , which was subjected to a vinylogous Mannich reaction to afford the pyrrolidine 167 (Scheme ).…”

Section: Synthesis Of Natural Products and Bioactive Moleculesmentioning

confidence: 99%

The Aza‐Prins Reaction in the Synthesis of Natural Products and Analogues

et al. 2017

View full text Add to dashboard Cite

International audienceThe classical Prins cyclization reaction has been one of the most studied reactions during the last two decades and it has found many applications in key steps of natural product syntheses, especially for products containing pyran units and related structures in their core skeletons. The nitrogen-based version of the Prins reaction, aza-Prins cyclization, has found its own relevance in organic synthesis owing to the fact that it gives direct access to piperidines, which are even more widespread in natural products and in drugs. Even though the potential scope of the reaction is vast, and despite it having afforded significant progress in the synthesis of various azaheterocycles, its applications in the field of natural product synthesis is massively underdeveloped in comparison with the classical Prins reaction. A compilation of the applications of azaPrins cyclization in the preparation of natural products and selected analogues, especially compounds of potential biological interest, is presented, with emphasis placed on the key roles of this reaction in the total synthesis of these products

show abstract

A new approach to the 8b-azaacenaphthylene ring system

Abstract: A stereoselective approach to the 8b-azaacenaphthylene ring system is described. This new route features a dichloroketene-enol ether [2 + 2] cycloaddition, a vinylogous Mannich reaction, and an aza-Prins cyclization as key stereoselective transformations.

Cited by 10 publications

References 40 publications

Short Synthesis of Alkaloid (−)-205B

Short Synthesis of Alkaloid (−)-205B

Diverse Natural Products from Dichlorocyclobutanones: An Evolutionary Tale

The Aza‐Prins Reaction in the Synthesis of Natural Products and Analogues

Contact Info

Product

Resources

About