Reactions of Levulinic Acid with Norbornane/ene Amino Acids and Diamines

We report a one-pot methodology for the synthesis of N-alkylated 2-substituted azetidin-3-ones based on a tandem nucleophilic substitution followed by intramolecular Michael reaction of primary amines with alkyl 5-bromo-4-oxopent-2-enoates, obtained in turn in three steps from levulinic acid. IntroductionSince the azetidin-3-one core has been used as a precursor for the synthesis of the natural sphingosine-type alkaloids penaresidines A and B and penazetidin A, [1] or as an intermediate in the synthesis of polyoxin antibiotics, [2,3] a number of different methodologies to obtain these fourmembered heterocycles have previously been described. [4] Cyclisation based on rhodium carbenoid intramolecular NH insertion has been developed by Seebach for the preparation of some azetidine-containing amino alcohol and amino acid derivatives [5] and by Vederas et al. for the synthesis of keto-glutamine analogues, [6] while De Kimpe has recently reported the synthesis of 4-alkyl-1-benzhydryl-2-(methoxymethyl)azetidin-3-ol as the result of stereoselective alkylation at the C-4 position of the corresponding azetidin-3-one obtained through a high-temperature reaction of an N-(diphenylmethylidene)-3-bromoamine precursor. [7] Azetidin-3-ones could also be obtained from the corresponding azetidin-3-ol precursors by use of pyridinium dichromate or Swern-type oxidation conditions. [8] As part of a recently started program aiming at the transformation of non-food/non-feed agricultural products, byproducts and waste materials into commodity chemicals we were interested in fine chemistry application of polyfunctionalised building blocks. One such derivative is 4-oxopentanoic acid or levulinic acid (LA; 1), traditionally obtained through the controlled degradation of hexose sugars by mineral acids.[9] The increasing number of patents directed towards the production of levulinic acid demonstrates its potential as an important basic chemical that could now be cost-efficiently produced from raw materials such as wood, [a] 2440A mechanistic interpretation of these reactions and an attempted enantioselective approach are also described. Germany, 2006) starch, cellulose-containing waste materials, recycled paper, or agricultural residues.[10]Beside its conversion into methyltetrahydrofuran, a fuel extender, or into δ-aminolevulinic acid, a biodegradable broad spectrum herbicide, [11] levulinic acid (1) also offers a great number of other synthetic transformations, [12] such as the synthesis of fused heterocycles prepared from norbornane amino acids and diamines [13] or the synthesis of the antibiotic lissoclinolide. [14] For a recent synthetic endeavour we needed ethyl 5-bromo-4-oxopent-2-enoate (3a) as key intermediate. This levulinic acid derivative appeared to be an even more versatile intermediate for further transformations such as Diels-Alder reactions, coupling reactions, nucleophilic substitutions and conjugate additions, and it was speculated that nucleophilic substitution combined with intramolecular Michael reaction should ope...

show abstract

“…In the 13 C NMR spectra, ketone and ester carbonyl signals were found at δ = 210-212 and 170-172 ppm, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…1 H NMR (300 MHz) and 13 C NMR (75 MHz) spectra were acquired on a Bruker AC 300 spectrometer in CDCl 3 , with TMS as internal standard.…”

Section: Methodsmentioning

confidence: 99%

A New Approach to the Synthesis of N‐Alkylated 2‐Substituted Azetidin‐3‐ones

2006

View full text Add to dashboard Cite

show abstract

“…[11] These products suggest some differences in the reactions of di-endo-and di-exo-norbornaneamino acids, resulting in elimination products such as 5, 6, 8, and 9, or in aza keto acetals similar to 7 and 10.…”

Section: Resultsmentioning

confidence: 99%

Indoloquinolines, Indolobenzoxazines and Quinazolophthalazines Prepared from Norbornane/eneamino Acids and Hydrazides

et al. 2005

Self Cite

View full text Add to dashboard Cite

Keywords: Indoloquinolines / Indolobenzoxazines / Quinazolophthalazines / NMR spectroscopy / DIFFNOE / X-ray diffractionThe reactions of di-endo-and di-exo-aminonorbornane/enecarboxylic acids 1-4 with ethyl 2-(2-oxocyclohexyl)acetate afforded methanoindoloquinolines 5, 6, 8, and 9, the oxo ester participating as a two-membered sp 2 building block. In the cases of di-exo-and di-endo-aminonorbornenecarboxylic acids 2 and 4, methanoindolobenzoxazinediones 7 and 10 were also formed; compound 7 was also isolated from the mother liquor of 10. The reactions of ethyl 2-(2-oxocy-

show abstract

“…The only exception is reaction of amino acids 31a/32a and 31b/32b or derivatives thereof with 1,4-dicarbonyl compounds like levullinic acid, leading to the (predominant) formation of products of the type 59 and 60, respectively. 49,50 The polycyclic compounds like those shown in Table 1 might remain just fanciful structures if their retro-Diels − Alder degradation was not discovered. The reaction was characteristic for the products derived from unsaturated amino acids 31/33, and virtually in all cases studied -from 31a,b (the exo isomers requiring milder conditions) (Scheme 16).…”

Section: Scheme 12mentioning

confidence: 99%

Bicyclic β-amino acids

Grygorenko

2015

Tetrahedron

View full text Add to dashboard Cite

Reactions of Levulinic Acid with Norbornane/ene Amino Acids and Diamines

Cited by 9 publications

References 23 publications

A New Approach to the Synthesis of N‐Alkylated 2‐Substituted Azetidin‐3‐ones

A New Approach to the Synthesis of N‐Alkylated 2‐Substituted Azetidin‐3‐ones

Indoloquinolines, Indolobenzoxazines and Quinazolophthalazines Prepared from Norbornane/eneamino Acids and Hydrazides

Bicyclic β-amino acids

Contact Info

Product

Resources

About