Dihydropyrrole-2-carboxylic acids

The synthesis of )-A -BOC-2-hydroxymethyl-2,5-dihydropyrrole )-923 with ee up to 98% was achieved by its irreversible acetylation catalyzed by Pseudomonas fluorescens lipase (Scheme 179) <1998TA403>. Precursor ( )-922 for compound 923 can be easily prepared from commercially available pyrrole-2-carboxylic acid 921 by Birch reduction, followed by esterification and reduction according to literature procedure <1996JOC7664>. 

It is evident that this addition/ring enlargement sequence has to be tested with other heterocumulenes too. So far only phenylthioisocyanate has been used, but completely analogous to CS2 dihydropyrrole derivatives 227 are now generated, which are either isolated or directly aromatized to pyrrole-3-carboxylates 228 after acid treatment (Eq. 93)97). 

Birch reduction of pyrrole carboxylic esters and tertiary amides gives dihydro-derivatives the presence of an electron-withdrawing gronp on the nitrogen serves both to remove the acidic iV-hydrogen and also to rednce the electron density on the ring. Quenching the immediate reduced species - an enolate - with an alkyl halide produces alkylated dihydropyrroles. ... 

These compounds were first introduced in Chapter 5 (Section 5.6) and many are key units in important pharmaceuticals. Compounds 47-50 are secondary amines and they react as bases in the presence of a suitable acid. One important compound that contains reduced heterocyclic rings is mitomycin C (51), an important drug used to treat cancer. In contains both an aziridine ring and dihydropyrrole units. 2-Azetidinecarboxylic acid (52) shows growth inhibitory activity on cultures of Escherichia coli. Several important compounds contain a pyrrolidine ring, including proline (53), which is a common amino acid (see Chapter 27). Nicotine (54) is found in tobacco, and the carboxylate salt of kainic acid (55) is a neurotoxin. 

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