Highly diastereoselective alkylation of aziridine-2-carboxylate esters: enantioselective synthesis of LFA-1 antagonist BIRT-377.

doi:10.1002/ANIE.200500923

Paper

Highly diastereoselective alkylation of aziridine-2-carboxylate esters: enantioselective synthesis of LFA-1 antagonist BIRT-377.

Published Sep 26, 2005 · A. Patwardhan, V. R. Pulgam, Yuzhang

Angewandte Chemie

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Abstract

Aziridines are important synthons in organic chemistry as they provide convenient entry to optically pure amines, aamino acids, amino alcohols, diamines, and a variety of other amino compounds that are useful both in industrial and academic endeavors. In the past, most optically pure aziridines were derived from acyclic members of the chiral pool, however, methods are emerging for the direct synthesis of optically pure aziridines through catalytic asymmetric reactions. We have developed a process for the catalytic asymmetric synthesis of aziridines from the reaction of benzhydryl imines with diazo compounds mediated by a chiral boron Lewis acid prepared from the VAPOL and VANOL ligands. This asymmetric aziridination (AZ) proved general for a range imines including those prepared from a variety of aryl aldehydes and also from primary, secondary, and tertiary aliphatic aldehydes (90–99% ee). Much lower enantioselectivities were observed with Nbenzyl imines. a-Amino acids which are tetrasubstituted at the a-carbon are very popular tools that are used to control conformation in peptides, and hence their biological and pharmaceutical properties. A large number of methods have been developed for the synthesis of tetrasubstituted a-amino acids, and this subject has been reviewed. Interestingly, aziridines have rarely been used for the synthesis of tetrasubstituted a-amino acids and this may be partly due to the fact that the alkylation of aziridine-2-carboxylates is virtually an unknown reaction. Typically, attempts to alkylate aziridine-2-carboxylate esters leads to either ring opening or to self-condensation. The only known examples involve the use of either thioesters of aziridine-2-carboxylates or the use of a nitrogen substituent on the aziridine that can chelate a metal enolate. A direct application of the AZ reaction to the synthesis of tetrasubstituted a-amino acids could be envisioned through the asymmetric aziridination of imine 1 with diazo compound

Study Snapshot

This study developed a catalytic asymmetric synthesis of aziridines from benzhydryl imines with diazo compounds, potentially enabling the synthesis of tetrasubstituted a-amino acids.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Highly diastereoselective alkylation of aziridine-2-carboxylate esters: enantioselective synthesis of LFA-1 antagonist BIRT-377.

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References

Total synthesis of LFA-1 antagonist BIRT-377 via organocatalytic asymmetric construction of a quaternary stereocenter.

The enantioselective total synthesis of LFA-1 antagonist BIRT-377 can be achieved through organocatalytic asymmetric construction of a quaternary stereocenter, with a one-pot trifluoro acetylation/selective benzyloxy

Synthesis of asymmetric iron–pybox complexes and their application to aziridine forming reactions

Asymmetric iron-pybox complexes can catalyze aziridine formation, producing 47% of cis-aziridine with a majority of side products consisting of trans-isomer and -amino-,-unsaturated esters.

The Brønsted acid-catalyzed direct aza-Darzens synthesis of N-alkyl cis-aziridines.

This method for synthesis of N-alkyl cis-aziridines using Brnsted acid is a mild, rapid, and environmentally friendly method with high stereocontrol.

Monomeric rhodium(II) catalysts for the preparation of aziridines and enantioselective formation of cyclopropanes from ethyl diazoacetate at room temperature.

Monomeric rhodium(II) catalysts provide excellent yields (66-94%) and enantioselectivity for cis product isomers in cyclopropanation of olefins by ethyl diazoacetate, with a preference for

LiClO4-catalyzed highly diastereoselective synthesis of cis-aziridine carboxylates

LiClO4-catalyzed synthesis of cis-aziridine carboxylates in high yields with high diastereoselectivity in mild and neutral conditions.

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