ChemInform Abstract: Preparation of Enantiopure β‐Amino Acids from α‐Amino Acids Using the Arndt‐Eistert Homologation

The synthesis of 3,4-dihydro-1,2-oxazepin-5(2H)-ones and 2,3-dihydropyridin-4(1H)-ones from β-substituted β-hydroxyaminoaldehydes is reported. The β-hydroxyaminoaldehydes were prepared by enantioselective organocatalytic 1,4-addition of N-tert-butyl (tert-butyldimethylsilyl)oxycarbamate to α,β-unsaturated aldehydes (MacMillan protocol). Alkyne addition to the aldehydes followed by alcohol oxidation furnished N-Boc O-TBS-protected β-aminoynones. Removal of the TBS protecting group initiated a 7-endo-dig cyclization to yield previously unknown 3,4-dihydro-1,2-oxazepin-5(2H)-ones. Reductive cleavage of the N–O bond of the oxazepinones and Boc-deprotection provided 2-substituted 2,3-dihydropyridin-4(1H)-ones via 6-endo-trig cyclization. 2,3-Dihydropyridin-4(1H)-ones are versatile intermediates that have been used for the synthesis of many alkaloids. The new protocol allows the synthesis of 3-dihydropyridin-4(1H)-ones carrying an array of substituents at C2 that cannot be prepared from commercial β-amino acids or by one-carbon homologation of proteinogenic amino acids. The use of readily available β-hydroxylaminoaldehydes expands the utility of our previously reported method to prepare 2,3-dihydropyridin-4(1H)-ones from β-amino acids as the source of diversity and chirality. A broad substrate scope is possible because β-aminoaldehydes can be prepared from α,β-unsaturated aldehydes by an enantioselective organocatalytic process.

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“…In the case of the Arndt–Eistert homologation, the handling of explosive diazomethane reagent is required. 45 − 47 …”

Section: Resultsmentioning

confidence: 99%

Enantioselective Synthesis of 3,4-Dihydro-1,2-oxazepin-5(2H)-ones and 2,3-Dihydropyridin-4(1H)-ones from β-Substituted β-Hydroxyaminoaldehydes

Ranade

Georg

2014

J. Org. Chem.

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“…For more details we refer to the list of references and to some review articles by us [10,40,44,50,65,67] and others [68][69][70], the latter ones also covering work on ß-peptides consisting of or containing cyclic ß-amino-acid residues, peptide analogs with N-N, N-O bonds or urea moieties incorporated in the backbone, or non-peptidic chains folding and turning.…”

Section: Resultsmentioning

confidence: 99%

“…As can be seen, they are available by classical organic name reactions. The β 3 - [50] and the y 4 -amino acid [51] derivatives are prepared from the natural α-amino acid precursors, while for the ß 2 -analogs enantioselective routes to substituted succinic acid esters [34,52] or enantioselective Mannich reactions [12] have to be employed. -peptides derived from proteinogenic L-amino acids (top).…”

Section: ß-And γ-Peptides -A Different Worldmentioning

confidence: 99%

Homologs of Amino Acids and Explorations into the Worlds of β‐ and γ‐Peptides

Seebàch

2002

Chemistry of Crop Protection

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In 1982 we have first become aware of the existence of the biopolymer PHB, consisting of (^)-3-hydroxybutanoates (HB), which we used as a source of readily available chiral building block for syntheses of natural products, such as elaiophylidin [I]. We then learned that short-chain PHB (ca. 150 HB units) is found in small amounts in all living cells and tissues, where it has been looked for (Figure 1), including plants, for instance O R [θ R or^^O· *-J Microbial storage material (s-PHB), R = Me, n ca. ΊΟ 4 BIOPOL®, R = Me/Et, n ca. 10 4 PHB in genetically modified plants , R = Me, n ca. 10 4 cPHB ( CaPPi complex; Ca-channel), R = Me, n ca. 150 E. CoIi: inner cell membrane when genetically competent (caused by Ca 2+ )Eukaryotic organisms: highest concentration in mitochondria Ca 2+ concentration mitochondrion/cytosol/extracellular 4 : 1 : 10 3 Human blood serum: 5-15 μg/ml, mainly bound to albumin which is the transport system for lipids and which is also binding ca. 40% of the serum Ca 2+ content Figure 1. The ubiquitous high-and low-molecular-weight biopolymer PHB is a microbial storage material (carbon and reductase equivalents, cf. Figure 2) and is found as part of ion-transporting systems in procaryotic and eucaryotic organisms, respectively [2].

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“…-Several diastereoselective methods to give b 2 -amino acids are described in the literature [20] [21]. One strategy for the synthesis of such building blocks is the highly diastereoselective aminoalkylation of N-acyloxazolidinone-derived titanium enolates with suitable electrophiles [22 -24].…”

mentioning

confidence: 99%

Benzyl N‐[(Benzyloxy)methyl]carbamate: An Improved Aminomethylation Electrophile for the Synthesis of (Benzyloxy)carbonyl (Cbz)‐Protected Chiral β²‐Amino Acids

Brocklehurst

Furegati

Müller-Hartwieg

et al. 2010

Helvetica Chimica Acta

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a-Aminomethylation of (R)-DIOZ-alkylated (DIOZ ¼ 4-isopropyl-5,5-diphenyloxazolidin-2-one) substrates is a key step in the asymmetric synthesis of b 2 -amino acids, but it is unfortunately often accompanied by formation of transcarbamation by-products. Aminomethylation was tested using a range of electrophiles, and the amount of by-product formation was assessed in each case. Benzyl N-[(benzyloxy)methyl]carbamate electrophile 3d is unable to form this by-product due to its inherent benzyl substitution. Use of electrophile 3d showed an improved impurity profile in aminomethylation, thus leading to easier intermediate purification.

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ChemInform Abstract: Preparation of Enantiopure β‐Amino Acids from α‐Amino Acids Using the Arndt‐Eistert Homologation

Cited by 8 publications

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Enantioselective Synthesis of 3,4-Dihydro-1,2-oxazepin-5(2H)-ones and 2,3-Dihydropyridin-4(1H)-ones from β-Substituted β-Hydroxyaminoaldehydes

Enantioselective Synthesis of 3,4-Dihydro-1,2-oxazepin-5(2H)-ones and 2,3-Dihydropyridin-4(1H)-ones from β-Substituted β-Hydroxyaminoaldehydes

Homologs of Amino Acids and Explorations into the Worlds of β‐ and γ‐Peptides

Benzyl N‐[(Benzyloxy)methyl]carbamate: An Improved Aminomethylation Electrophile for the Synthesis of (Benzyloxy)carbonyl (Cbz)‐Protected Chiral β²‐Amino Acids

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ChemInform Abstract: Preparation of Enantiopure β‐Amino Acids from α‐Amino Acids Using the Arndt‐Eistert Homologation

Cited by 8 publications

References 0 publications

Enantioselective Synthesis of 3,4-Dihydro-1,2-oxazepin-5(2H)-ones and 2,3-Dihydropyridin-4(1H)-ones from β-Substituted β-Hydroxyaminoaldehydes

Enantioselective Synthesis of 3,4-Dihydro-1,2-oxazepin-5(2H)-ones and 2,3-Dihydropyridin-4(1H)-ones from β-Substituted β-Hydroxyaminoaldehydes

Homologs of Amino Acids and Explorations into the Worlds of β‐ and γ‐Peptides

Benzyl N‐[(Benzyloxy)methyl]carbamate: An Improved Aminomethylation Electrophile for the Synthesis of (Benzyloxy)carbonyl (Cbz)‐Protected Chiral β2‐Amino Acids

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Benzyl N‐[(Benzyloxy)methyl]carbamate: An Improved Aminomethylation Electrophile for the Synthesis of (Benzyloxy)carbonyl (Cbz)‐Protected Chiral β²‐Amino Acids