Amino Acid Homologation by the Blaise Reaction: A New Entry into Nitrogen Heterocycles

Abstract

A general strategy for the amino acid homologation via Blaise reaction and subsequent reduction is presented. This strategy involves the preparation of protected alpha-amino nitriles from the corresponding amino acids, followed by the zinc-mediated condensation of tert-butyl bromoacetate, to give the imidazolidones after iminozincate cyclization. Reduction gave the saturated imidazolidinones with cis or trans stereochemistry, depending on the reduction conditions. This strategy was applied to nonfunctionalized amino acids and to functionalized amino acids such as serine and aspartic acid. Additionally, acidic hydrolysis of cis or trans imidazolidinones to the corresponding chiral 4-aminopyrrolidones is described.

Highly Functionalized 1,2–Diamino Compounds through Reductive Amination of Amino Acid-Derived β–Keto Esters

“…These cyclic compounds can illustrate one example of the application of the described diamino esters in the creation of diverse heterocyclic scaffolds of interest. Related pyrrolidinone derivatives, having an unsubstituted 4-amino group, have been prepared through the Zinc-mediated homologation of α-aminonitriles and subsequent acidic hydrolysis [37]. The J 4,5 in derivatives 7a , 7c and 8a (∼6.5 Hz) was higher than in their corresponding distereoisomers 7b and 8b (∼4.5 ppm).…”

Interactions of Aromatic Radicals with Water

“…[9] Matrix Isolation Matrix isolation experiments were performed by standard techniques using an APD HC-4 closed cycle helium compressor for cooling to 10 K. For studies in the mid IR range (400 and 4000 cm À1 ), matrices were deposited on CsI spectroscopic windows, and the spectra recorded on FTIR spectrometers with a standard resolution of 0.5 cm À1 . Benzyl iodide 8 was synthesized according to a literature procedure (Scheme 2).…”

Acyclic and Cyclic Ureas (Update 2013)

“…[164] A multistep sequence for the preparation of imidazolidin-2-ones involves zinc-mediated condensation of carbamate-protected a-amino nitriles, obtained from the corresponding a-amino acids, with tert-butyl bromoacetate followed by cyclization. [165] for references see p 301…”