Stereodivergent Synthesis of Piperidine Alkaloids by Ring‐Rearrangement Metathesis/Reductive Lactam Alkylation of Nitroso Diels–Alder Cycloadducts

Vincent, Guillaume; Karila, Delphine; Khalil, Georges; Sancibrao, Pierre; Gori, Davide; Kouklovsky, Cyrille

doi:10.1002/chem.201300836

Cited by 47 publications

(10 citation statements)

References 88 publications

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“…Indirect methods require a preactivation step, which is a transformation of the amide functionality into a more reactive species, for example, an acylamide (DeNinno,3a Suh)3c or thioamide (Murai) 3d. e Direct methods, without the preactivation step, proved possible by using tert ‐formamides (de Meijere,3f Bélanger),3i tert ‐amides (Huang),3g, h, m–o sec ‐amides (Huang),3k and N‐alkoxyamides (Kibayashi,4f Sato and Chida,4a, b Vincent and Kouklovsky,4c, d Helmchen) 4e. However, the chemoselective version of the reaction has remained a formidable challenge because of the use of reactive organometallic reagents such as Grignard reagents and organolithium reagents prohibits functional‐group compatibility with sensitive functional groups 7.…”

Section: Introductionmentioning

confidence: 99%

Chemoselective Reductive Nucleophilic Addition to Tertiary Amides, Secondary Amides, and N‐Methoxyamides

Nakajima

Oda

Wada

et al. 2014

Chemistry A European J

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As the complexity of targeted molecules increases in modern organic synthesis, chemoselectivity is recognized as an important factor in the development of new methodologies. Chemoselective nucleophilic addition to amide carbonyl centers is a challenge because classical methods require harsh reaction conditions to overcome the poor electrophilicity of the amide carbonyl group. We have successfully developed a reductive nucleophilic addition of mild nucleophiles to tertiary amides, secondary amides, and N-methoxyamides that uses the Schwartz reagent [Cp2 ZrHCl]. The reaction took place in a highly chemoselective fashion in the presence of a variety of sensitive functional groups, such as methyl esters, which conventionally require protection prior to nucleophilic addition. The reaction will be applicable to the concise synthesis of complex natural alkaloids from readily available amide groups.

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Section: Introductionmentioning

confidence: 99%

Chemoselective Reductive Nucleophilic Addition to Tertiary Amides, Secondary Amides, and N‐Methoxyamides

Nakajima

Oda

Wada

et al. 2014

Chemistry A European J

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“…Kouklovsky and co-workers [ 62 ] have described a stereoselective synthesis of 2-(2-hydroxyalkyl)piperidine alkaloids by employing a RRM of NDA adduct 293 . The required building block 293 has been prepared via NDA reaction of compound 292 and cyclopentadiene ( 111 ).…”

Section: Reviewmentioning

confidence: 99%

Recent applications of ring-rearrangement metathesis in organic synthesis

Kotha¹,

Meshram²,

Khedkar³

et al. 2015

Beilstein J. Org. Chem.

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SummaryRing-rearrangement metathesis (RRM) involves multiple metathesis processes such as ring-opening metathesis (ROM)/ring-closing metathesis (RCM) in a one-pot operation to generate complex targets. RRM delivers complex frameworks that are difficult to assemble by conventional methods. The noteworthy point about this type of protocol is multi-bond formation and it is an atom economic process. In this review, we have covered literature that appeared during the last seven years (2008–2014).

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“…This stereodivergent procedure has been applied to the formal synthesis of porantheridine 188 and to the asymmetric total synthesis of andrachcinidine,103 and allowed a dramatic simplification of their previous synthesis of porantheridine (Scheme ) 104. In fact, the first synthesis was based on the addition of allylMgBr–NaBH 3 CN to an N ‐benzyl‐protected lactam 186 in analogy to the previously discussed Fowler strategy 55a.…”

Section: Synthesis Of N‐alkoxy Amines and Related Compoundsmentioning

confidence: 99%

Increasing the Reactivity of Amides towards Organometallic Reagents: An Overview

2014

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The nucleophilic addition of carbon nucleophiles to amides has traditionally been a difficult task, both due to reactivity and selectivity problems. When successful, these processes would represent straightforward routes towards carbonyl‐type or amine compounds, depending on the fate of the generated tetrahedral intermediate. The direct addition of nucleophiles to amides for the preparation of ketones has been studied and applied to the syntheses of several natural products. On the other hand, the addition of nucleophiles to amides to obtain substituted amines represented a major challenge, and only scattered applications on particular substrates have appeared. Initial improvements were based on the activation of amides by introduction of particular substituents, such as in N‐methoxy amides (Weinreb amides) or electron‐withdrawing groups able to increase the carbon nucleophilicity. Although these strategies facilitate the introduction of nucleophiles, chemoselectivity issues arise when additional electrophilic moieties (i.e., carbonyls) are present, thus decreasing the versatility of the methods. In recent years, important advancements towards fully chemoselective methods have been realized. The capture of tetrahedral intermediates with acids generates highly electrophilic iminium species able to undergo chemoselective additions of various nucleophiles, thus accessing substituted amines. Alternatively, the in situ generation of an iminium triflate ion allows highly chemoselective additions of nucleophiles, yielding amines, ketones or ketimines. Also thioamides can be used as precursors of ketones or α‐substituted amines. The success of the above methodologies is further showcased by the application in various syntheses of natural products or biologically active molecules.

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Stereodivergent Synthesis of Piperidine Alkaloids by Ring‐Rearrangement Metathesis/Reductive Lactam Alkylation of Nitroso Diels–Alder Cycloadducts

Cited by 47 publications

References 88 publications

Chemoselective Reductive Nucleophilic Addition to Tertiary Amides, Secondary Amides, and N‐Methoxyamides

Chemoselective Reductive Nucleophilic Addition to Tertiary Amides, Secondary Amides, and N‐Methoxyamides

Recent applications of ring-rearrangement metathesis in organic synthesis

Increasing the Reactivity of Amides towards Organometallic Reagents: An Overview

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