Diastereoselective Cationic Tandem Cyclizations to <i>N</i>-Heterocyclic Scaffolds:  Total Synthesis of (−)-Dysibetaine PP

IJzendoorn, Denis R.; Botman, Peter N. M.; Blaauw, Richard H.

doi:10.1021/ol052598r

Cited by 40 publications

(22 citation statements)

References 11 publications

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“…Imidazolidin-4-one is an important structural moiety existed in many natural products [(-)-Dysibetaine PP], [1] pharmaceuticals [Hetacillin], [2] and privileged scaffolds of anticonvulsant compounds [3] and antimalarial agents [4] (Figure 1). Similar imidazolones were also found in both natural products and pharmaceut-icals such as Kottamide, [5] SCH900822, GSK2137305, [6] and Glucagon Receptor Antagonists.…”

mentioning

confidence: 99%

A Decarboxylative C(sp³)−N Bond Forming Reaction to Construct 4‐Imidazolidinones via Post‐Ugi Cascade Sequence in One Pot

Song

Lei

et al. 2020

Adv Synth Catal

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A post-Ugi one-pot cascade was developed to access 4-imidazolidinones through an intramolecular decarboxylative C(sp 3)À N bond forming reaction. The reaction has a broad tolerance for a variety of substituted aldehydes, anilines, isocyanides and glyoxylic acids. The cascade reaction scope was expanded to synthesize spiroimidazolidinone by the replacement of aldehyde with aliphatic ketone in the Ugi reaction. Subsequently, the methodology was applied to synthesize the core structures of pharmaceuticals GSK2137305 and SCH 900822 under the mild and facile conditions with one purification. This cascade reaction generates opportunities for the tailored synthesis of a range of biologically active 4-imidazolidinones through tuneable Ugi inputs.

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confidence: 99%

A Decarboxylative C(sp³)−N Bond Forming Reaction to Construct 4‐Imidazolidinones via Post‐Ugi Cascade Sequence in One Pot

Song

Lei

et al. 2020

Adv Synth Catal

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“…As an example, a diastereoselective cationic domino cyclisation was employed by Blaauw et al as the key step in a total synthesis of the natural product (-)-dysibetaine PP. 51 As shown in Scheme 1.33, treatment of various enantiopure dipeptides by a catalytic amount of 4-toluenesulfonyl (Ts)OH underwent the formation of the corresponding bicyclic N,N-acetals through cascade cationic cyclisations in good yields and diastereoselectivities of up to 88% de in favour of the transisomer. This methodology was applied to a chiral dipeptide derived from L-allysine to give the corresponding amine, which was further converted into (-)-dysibetaine PP.…”

Section: Cationic Sequencesmentioning

confidence: 99%

Asymmetric Domino Reactions Based on the Use of Chiral Substrates

2013

Asymmetric Domino Reactions

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This chapter updates the recent developments in asymmetric one-, two-, and multicomponent domino reactions which involve chiral substrates. It is divided into two sections, dealing successively with one- and two-component domino reactions, and with multicomponent domino reactions. The first section is subdivided into eight sections, describing domino reactions with an anionic primary step, domino reactions based on cationic sequences, domino reactions initiated by a pericyclic primary step, domino reactions based on carbene sequences, palladium-catalysed domino reactions, ruthenium-catalysed domino reactions, gold-catalysed domino reactions, and finally miscellaneous domino reactions. The second section of the chapter is subdivided into 10 sections, dealing with multicomponent reactions initiated by the Michael addition, multicomponent reactions based on the Hantzsch reaction, multicomponent reactions based on the Ugi reaction, multicomponent reactions based on the Strecker reaction, multicomponent reactions based on the Mannich reaction, multicomponent reactions initiated by an allylation reaction, multicomponent reactions based on the Passerini reaction, multicomponent reactions based on the Biginelli reaction, multicomponent reactions based on the Petasis reaction, and finally miscellaneous multicomponent reactions. The power and utility of these reactions are well illustrated by their application in the synthesis of a wide range of structurally diverse and complex chiral molecules.

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“…Although both path A and path B involve a geometrically unfavourable 5-endotrig cyclisation, the observed cyclisations do proceed smoothly when the amide nitrogen atom acts as a nucleophile to add onto an N-acyliminium ion intramolecularly. [24][25][26] Apparently, in the presence of TsOH, compounds 8a-d prefer to cyclise into 11 rather than producing 12 due to the presence of a more extensive p-conjugated system in 11.…”

Section: Scheme 1 Synthesis Of A-amino Acid Based Biaryls 8a-dmentioning

confidence: 99%

Asymmetric Synthesis of Novel Biaryl Analogues with a Fused Chiral Bicyclic Bridge Using α-Amino Acids as Chiral Sources

Zhao¹,

Xiao²,

Cui³

et al. 2011

Synlett

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A series of biaryl anologues with a fused bicyclic bridge were synthesised in a diastereoselectivity of up to 14:86 via an intramolecular cyclisation of an in situ generated N-acyliminium ion. The absolute configuration of products 9b-d and 10b-d was clearly defined by a combination of X-ray crystal-structural analysis, NOE difference, and CD experiments.Axially enantiopure biaryls are highly important molecules and are widely used in asymmetric catalysis, 1,2 medicinal, 3-9 and supramolecular chemistry. 10 It has been documented that the pharmacological properties of bioactive chiral biaryls are mainly governed by the stereogenic configuration of biaryl axes 11,12 and that the catalytic reactivity and stereoselectivity of biaryl catalysts are also significantly affected by the axial chirality. Due to the unique stereochemical characteristics of biaryl compounds, a number of excellent asymmetric methodologies have been developed for the atroposelective synthesis of rotationally hindered biaryl compounds. [13][14][15][16][17][18] In this work, we wish to report a new approach to the synthesis of a series of conformationally restrained biaryls 9 and 10 containing a fused chiral bicyclic bridge (Table 1). Using a-amino acids as chiral sources, the construction of the target molecules was accomplished diastereoselectively via a cascade cyclisation involving the initial formation of a cyclic N-acyliminium ion intermediate, followed by a second diastereoselective intramolecular cyclisation with a nitrogen-based nucleophile. 19The key acyclic precursors 8a-d were synthesised in 83-97% yields based on the strategy developed by us previously (Scheme 1). 20 It was indicated by 1 H NMR spectral data that compounds 8b-d existed as a mixture of two inseparable diastereoisomers in a ratio of about 70:30. The cyclisation reaction of compounds 8b-d were carried out in the presence of TsOH (Table 1). 21 In the cyclisation reactions, compounds 10b-d were obtained as major diastereoisomers and 9b-d as minor diastereoisomers. For example, compound (R)-8b was cyclised to give a 35:65 diastereoisomeric mixture of (2R,12bR,P)-9b and (2R,12bS,M)-10b, and the two diastereoisomers can be readily separated by flash column chromatography on silica gel. For compound (R)-8c, diastereoisomers (2R,12bR,P)-9c and (2R,12bS,M)-10c were obtained in a diastereoisomeric ratio of 14:86. Apparently, the cyclisation of (R)-8c gave the products with higher diastereoselectivity as compared to that of compound (R)-8b. Scheme 1 Synthesis of a-amino acid based biaryls 8a-dIn the case of compound (R)-8d, a diastereoisomeric mixture of (2R,12bR,P)-9d and (2R,12bS,M)-10d was provided in a 15:85 ratio. Accordingly, compounds (R)-8c and (R)-8d exhibited a similar degree of diastereoselectivity in the cyclisation reactions. Obviously, the diastereoselectivities of the products from the antipodal (S)-8b-d were the same as those of (R)-8b-d. It should be pointed out toluene 110 °C Pd(PPh 3 ) 4 CuBr, THF reflux TsOH, benzene 80 °C EtOH, r.t. H 2 , PtO 2 1 NO 2 Br NO ...

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Diastereoselective Cationic Tandem Cyclizations to N-Heterocyclic Scaffolds: Total Synthesis of (−)-Dysibetaine PP

Cited by 40 publications

References 11 publications

A Decarboxylative C(sp³)−N Bond Forming Reaction to Construct 4‐Imidazolidinones via Post‐Ugi Cascade Sequence in One Pot

A Decarboxylative C(sp³)−N Bond Forming Reaction to Construct 4‐Imidazolidinones via Post‐Ugi Cascade Sequence in One Pot

Asymmetric Domino Reactions Based on the Use of Chiral Substrates

Asymmetric Synthesis of Novel Biaryl Analogues with a Fused Chiral Bicyclic Bridge Using α-Amino Acids as Chiral Sources

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Diastereoselective Cationic Tandem Cyclizations to N-Heterocyclic Scaffolds: Total Synthesis of (−)-Dysibetaine PP

Cited by 40 publications

References 11 publications

A Decarboxylative C(sp3)−N Bond Forming Reaction to Construct 4‐Imidazolidinones via Post‐Ugi Cascade Sequence in One Pot

A Decarboxylative C(sp3)−N Bond Forming Reaction to Construct 4‐Imidazolidinones via Post‐Ugi Cascade Sequence in One Pot

Asymmetric Domino Reactions Based on the Use of Chiral Substrates

Asymmetric Synthesis of Novel Biaryl Analogues with a Fused Chiral Bicyclic Bridge Using α-Amino Acids as Chiral Sources

Contact Info

Product

Resources

About

A Decarboxylative C(sp³)−N Bond Forming Reaction to Construct 4‐Imidazolidinones via Post‐Ugi Cascade Sequence in One Pot

A Decarboxylative C(sp³)−N Bond Forming Reaction to Construct 4‐Imidazolidinones via Post‐Ugi Cascade Sequence in One Pot