Limits...
Pd-catalysed ligand-enabled carboxylate-directed highly regioselective arylation of aliphatic acids

View Article: PubMed Central - PubMed

ABSTRACT

α-amino acids bearing aromatic side chains are important synthetic units in the synthesis of peptides and natural products. Although various β-C-H arylation methodologies for amino acid derivatives involving the assistance of directing groups have been extensively developed, syntheses that directly employ N-protected amino acids as starting materials remain rare. Herein, we report an N-acetylglycine-enabled Pd-catalysed carboxylate-directed β-C(sp3)-H arylation of aliphatic acids. In this way, various non-natural amino acids can be directly prepared from phthaloylalanine in one step in good to excellent yields. Furthermore, a series of aliphatic acids have been shown to be amenable to this transformation, affording β-arylated propionic acid derivatives in moderate to good yields. More importantly, this ligand-enabled direct β-C(sp3)-H arylation could be easily scaled-up to 10 g under reflux conditions, highlighting the potential utility of this synthetic method.

No MeSH data available.


Ten gram scale reaction in one step.Arylation of N-phthaloyl-phenylalanine (1a) on a 10 g scale.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5384235&req=5

f4: Ten gram scale reaction in one step.Arylation of N-phthaloyl-phenylalanine (1a) on a 10 g scale.

Mentions: Considering the importance of the generated non-natural amino acids, if this newly developed carboxylate-assisted directed C(sp3)-H arylation could be performed on a 10 g scale, it would provide a very attractive and convenient approach for the synthesis of phenylalanine derivatives in the laboratory. To our delight, 10 g scale reactions proceeded well with a range of aryl iodides (Fig. 4, 3a, 10.56 g; 3h, 10.97 g; 3o, 12.88 g) by employing a slightly longer reaction time, even under reflux conditions.


Pd-catalysed ligand-enabled carboxylate-directed highly regioselective arylation of aliphatic acids
Ten gram scale reaction in one step.Arylation of N-phthaloyl-phenylalanine (1a) on a 10 g scale.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5384235&req=5

f4: Ten gram scale reaction in one step.Arylation of N-phthaloyl-phenylalanine (1a) on a 10 g scale.
Mentions: Considering the importance of the generated non-natural amino acids, if this newly developed carboxylate-assisted directed C(sp3)-H arylation could be performed on a 10 g scale, it would provide a very attractive and convenient approach for the synthesis of phenylalanine derivatives in the laboratory. To our delight, 10 g scale reactions proceeded well with a range of aryl iodides (Fig. 4, 3a, 10.56 g; 3h, 10.97 g; 3o, 12.88 g) by employing a slightly longer reaction time, even under reflux conditions.

View Article: PubMed Central - PubMed

ABSTRACT

α-amino acids bearing aromatic side chains are important synthetic units in the synthesis of peptides and natural products. Although various β-C-H arylation methodologies for amino acid derivatives involving the assistance of directing groups have been extensively developed, syntheses that directly employ N-protected amino acids as starting materials remain rare. Herein, we report an N-acetylglycine-enabled Pd-catalysed carboxylate-directed β-C(sp3)-H arylation of aliphatic acids. In this way, various non-natural amino acids can be directly prepared from phthaloylalanine in one step in good to excellent yields. Furthermore, a series of aliphatic acids have been shown to be amenable to this transformation, affording β-arylated propionic acid derivatives in moderate to good yields. More importantly, this ligand-enabled direct β-C(sp3)-H arylation could be easily scaled-up to 10 g under reflux conditions, highlighting the potential utility of this synthetic method.

No MeSH data available.