ChemInform Abstract: Stereoselective Syntheses of Heterocycles with Lithiated Methoxyallene

Reißig, Hans‐Ulrich; Hormuth, Stephan; Schade, Wolfgang; Amombo, Marlyse Okala; Watanabe, Tetsu; Pulz, Robert; Hausherr, Arndt; Zimmer, Reinhold

doi:10.1002/chin.200039259

Cited by 4 publications

(8 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Treatment of 274 with Pd(II) reagents in the absence of an alkenyl component gave only traces of the Δ 1 -carbapenem 276 . More successful was a similar palladium-catalyzed cyclization of a methoxyallene derivative, which formed the dihydropyrrole 277 74 …”

Section: Reactions Of Allenes With Heteroatom Nucleophilesmentioning

confidence: 99%

Palladium-Catalyzed Reactions of Allenes

et al. 2000

Self Cite

View full text Add to dashboard Cite

Section: Reactions Of Allenes With Heteroatom Nucleophilesmentioning

confidence: 99%

Palladium-Catalyzed Reactions of Allenes

et al. 2000

Self Cite

View full text Add to dashboard Cite

“…4 Lithiated methoxyallene 2 is an extremely valuable building block for the synthesis of oxygen and nitrogen heterocycles. 5 With carbonyl compounds it provides furan derivatives after cyclization, 6 whereas its reaction with nitrones leads to 1,2-oxazines. 7 Surprisingly, no additions to simple imines have been reported, 8 which should furnish pyrrole derivatives.…”

mentioning

confidence: 99%

An Expedient Synthesis of Pyrrole Derivatives by Reaction of Lithiated Methoxyallenes with Imines

Amombo¹,

Hausherr²,

Reißig³

1999

Synlett

Self Cite

View full text Add to dashboard Cite

Addition of lithiated methoxyallene 2 to imines provided the expected allenyl amines in good yield. These could be cyclized with base or with silver nitrate to a variety of 2,5-dihydropyrrole derivatives. Selected examples describe their conversion to pyrrolidin-3-ones or 3-methoxypyrroles. Most importantly, this [3+2] cyclization method could also be applied to the synthesis of 2,5-disubstituted derivatives such as 26-28 and also to the preparation of the enantiopure compound 23.Syntheses of pyrrole derivatives are of great importance due to their presence in numerous biologically active compounds. 2 Therefore, many routes leading to this class of heterocycles have been developed. 3 In addition, certain electron-rich pyrrole derivatives are of interest because of their redox behaviour and their ability to provide polypyrroles. 4 Lithiated methoxyallene 2 is an extremely valuable building block for the synthesis of oxygen and nitrogen heterocycles. 5 With carbonyl compounds it provides furan derivatives after cyclization, 6 whereas its reaction with nitrones leads to 1,2-oxazines. 7 Surprisingly, no additions to simple imines have been reported, 8 which should furnish pyrrole derivatives. A recent publication describing reactions of 2 with SAMP-hydrazones providing enantiopure 3-methoxy-2,5-dihydropyrrole derivatives 9 prompts us to report our results with various imines. 10 Lithiated methoxyallene 2 was generated by the standard procedure employing n-butyllithium at -40°C, and after addition of N-tosylimine 1 11 followed by aqueous workup and purification the primary adduct 3 was obtained in 67% yield (Scheme 1). This intermediate could be hydrolyzed with acid to afford an a,ß-unsaturated ketone 10 or, more interestingly, converted into a-amino ester 4 by ozonolysis. 12In analogy to the behaviour of the carbonyl adducts 6 cyclization of 3 employing 0.15 equivalents of potassium tert-butoxide in DMSO furnished the desired pyrrole derivative 6 in 84% yield. Since an excess of base converts 6 into 5, the isomerization 3AE6 is better performed by using of 0.27 equivalents of silver nitrate in acetone 13 which gave a yield of 93%. 14 Cyclization of 3 and elimination of toluene sulfinate from intermediate 6 proceeded by use of 1.5 equivalents of KOtBu and furnished 3-methoxy-2-phenylpyrrole (5) in 71% yield. This compound was also formed by heating the primarily obtained lithium salt of 3 in DMSO. An obvious subsequent transformation of 2,5-dihydropyrrole derivative 6 is the hydrolysis of its enol ether moiety; treatment of 6 with 2N aqueous sulfuric acid provided pyrrolidinone 7 in 96% yield. Analogous experiments were successfully performed with N-tosyl imines derived from pivalaldehyde and cinnamyl aldehyde. Having established that highly reactive imines such as 1 behave similarly to carbonyl compounds, we studied less reactive N-aryl and N-alkyl imines. Scheme 2 presents selected examples of the additions of 2 to readily available imines 8, 10, 12, 15, and 17. Cyclization either with silver nitrate or under basic ...

show abstract

“…All the examples collected here show the potential of this approach to highly functionalized heterocycles, furnishing compounds with a very high degree of structural diversity that should be of interest in drug synthesis or material science. The versatility of alkoxyallenes [ 11 – 20 65 – 66 ] as easily available C 3 building blocks is key for this prosperousness.…”

Section: Discussionmentioning

confidence: 99%

“…Not surprisingly, simple or functionalized allenes have also been used in multicomponent processes and – dependent on the substitution pattern of the allene – a remarkable variety of reactions and product types are known using the three-carbon backbone of these reactive compounds [ 10 ]. During the exploration of alkoxyallene chemistry [ 11 – 20 ] we accidently discovered a new three-component reaction leading to β-ketoenamides that are uniquely functionalized alkenes and suitable for a variety of subsequent reactions, in particular in heterocyclic synthesis.…”

Section: Introductionmentioning

confidence: 99%

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

Lechel

Kumar

Bera

et al. 2019

Beilstein J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

The LANCA three-component reaction of lithiated alkoxyallenes LA, nitriles N and carboxylic acids CA leads to β-ketoenamides KE in good to excellent yields. The scope of this reaction is very broad and almost all types of nitriles and carboxylic acids have successfully been used. The alkoxy group introduced via the allene component is also variable and hence the subsequent transformation of this substituent into a hydroxy group can be performed under different conditions. Enantiopure nitriles or carboxylic acids can also be employed leading to chiral KE with high enantiopurity and dinitriles or dicarboxylic acids also lead to the expected bis-β-ketoenamides. β-Ketoenamides incorporate a unique combination of functional groups and hence a manifold of subsequent reactions to highly substituted heterocyclic compounds is possible. An intramolecular aldol-type condensation reaction efficiently furnishes pyridin-4-ols PY that can be further modified by palladium-catalyzed reactions, e.g., to specifically substituted furopyridine derivatives. Condensations of β-ketoenamides with ammonium salts or with hydroxylamine hydrochloride afford pyrimidines PM or pyrimidine N-oxides PO with a highly flexible substitution pattern in good yields. The functional groups of these heterocycles also allow a variety of subsequent reactions to various pyrimidine derivatives. On the other hand, acid-labile alkoxy substituents such as a 2-(trimethylsilyl)ethoxy group are required for the conversion of β-ketoenamides into 5-acetyl-substituted oxazoles OX, again compounds with high potential for subsequent functional group transformations. For acid labile β-ketoenamides bearing bulky substituents the acid treatment leads to acylamido-substituted 1,2-diketones DK that could be converted into quinoxalines QU. All classes of heterocycles accessed through the key β-ketoenamides show a unique substitution pattern – not easily accomplishable by alternative methods – and therefore many subsequent reactions are possible.

show abstract

ChemInform Abstract: Stereoselective Syntheses of Heterocycles with Lithiated Methoxyallene

Cited by 4 publications

References 1 publication

Palladium-Catalyzed Reactions of Allenes

Palladium-Catalyzed Reactions of Allenes

An Expedient Synthesis of Pyrrole Derivatives by Reaction of Lithiated Methoxyallenes with Imines

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

Contact Info

Product

Resources

About