Ethyl N-(Diphenylmethylene)-2-acetoxyglycinate

(R = Et)

[97611-55-7]  · C19H19NO4  · Ethyl N-(Diphenylmethylene)-2-acetoxyglycinate  · (MW 325.36) (R = Me)

[130551-77-8]  · C18H17NO4  · Methyl N-(Diphenylmethylene)-2-acetoxyglycinate  · (MW 311.34) (R = Bn)

[130946-34-8]  · C24H21NO4  · Benzyl N-(Diphenylmethylene)-2-acetoxyglycinate  · (MW 387.43)

(glycine cation equivalent for amino acid synthesis)

Alternate Names: ethyl a-acetoxyglycinate benzophenone imine; O'Donnell's Schiff base.

Physical Data: R = Me, mp 102-103 °C; R = Et, mp 62-65 °C; R = Bn, mp 63-64 °C.

Preparative Methods: by bromination of ethyl N-(diphenylmethylene)glycinate in the presence of acetate (NBS, NaOAc, DMF).1 The crude product can be purified by recrystalization. (Et2O/hexane).

Handling, Storage, and Precautions: although stable at room temperature, the compound is normally stored under argon in the freezer. The hydrolysis product, benzophenone, can be detected either by TLC (EtOAc/hexane) or by NMR.

Complementary Synthons for Amino Acid Chemistry.

The acetate Schiff base ester can react as a glycine cation equivalent with a variety of nucleophiles to replace the acetate group. The resulting products are often difficult to prepare using the complementary anionic glycine equivalent (see Ethyl N-(Diphenylmethylene)glycinate) (eq 1).

Reaction with Heteroatom Nucleophiles.

Reaction with alcohols (methyl, primary, secondary) or thiophenol replaces the acetoxy group with a new a-heteroatom group (eq 2). These products can themselves be used as cationic glycinates for further reaction with nucleophiles.1

Reaction with Carbon Nucleophiles.

Reaction with higher order mixed cuprates results in a,b carbon-carbon bond formation (eq 3). This provides preparations of aryl and heteroaryl glycine derivatives as well as a-monosubstituted amino acids containing a b-quaternary center (e.g. t-butylglycine).2

Neutral carbon nucleophiles such as activated aromatics or organosilicon reagents react in the presence of Titanium(IV) Chloride to yield aryl and heteroaryl glycines as well as g,d-unsaturated or g-keto amino acid derivatives (eq 4).3

Reaction with organoboranes allows for effective appendage of the amino acid substructure onto structures that can be converted into organoboranes (e.g. alkenes, organolithium reagents, aryl halides, hydrocarbons, etc.) (eq 5).4

Reaction of the methyl ester acetate Schiff base with anions of active methylene compounds (soft nucleophiles) in the presence of a Pd0 catalyst results in carbon-carbon bond formation (eq 6). The reaction likely occurs through a 2-aza-p-allyl palladium complex.5

Related Reagents.

Benzophenone Imine; Methyl 2-Bromo-N-(t-butoxycarbonyl)glycinate; N-(Diphenylmethylene)aminoacetonitrile; Ethyl N-(Diphenylmethylene)glycinate; Methyl Glyoxylate; 8-Phenylmenthyl Glyoxylate.

1. O'Donnell, M. J.; Bennett, W. D.; Polt, R. L. TL 1985, 26, 695.
2. O'Donnell, M. J.; Falmagne, J.-B. TL 1985, 26, 699.
3. O'Donnell, M. J.; Bennett, W. D. T 1988, 44, 5389.
4. O'Donnell, M. J.; Falmagne, J.-B. CC 1985, 1168.
5. O'Donnell, M. J.; Yang, X.; Li, M. TL 1990, 31, 5135.

Martin J. O'Donnell

Indiana University-Purdue University at Indianapolis, IN, USA

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