Elsevier

Tetrahedron

Volume 65, Issue 4, 24 January 2009, Pages 831-843
Tetrahedron

The asymmetric aminohydroxylation route to GABOB and homoserine derivatives

https://doi.org/10.1016/j.tet.2008.11.037Get rights and content

Abstract

The 4-nitrophenyl ether is an efficient directing group in the asymmetric aminohydroxylation reaction of homoallylic ether derivatives. Either regioisomeric product can be obtained with useful levels of enantioselectivity allowing for the short enantioselective synthesis of GABOB and homoserine derivatives. A model based on substrate-catalyst interactions is presented to explain the regio- and enantioselectivity of the aminohydroxylation reactions.

Introduction

The osmium-catalysed asymmetric aminohydroxylation (AA) of alkenes has become a powerful tool for the synthesis of the vicinal amino alcohol functional array and has been applied to the construction of numerous biologically important targets.1, 1(a), 1(b), 1(c), 1(d), 1(e), 1(f), 1(g), 1(h), 1(i), 1(j), 1(k), 1(l), 1(m), 1(n), 1(o), 1(p), 1(q) Despite this success, the levels of regio- and enantioselectivity obtained for some alkene substitution patterns are not always synthetically useful.

Research within our laboratory2, 3, 4 and by other groups5, 6, 7 has shown that the interaction of substrate and catalyst plays a pivotal role in controlling selectivity in the AA reaction. In a previous study3 we demonstrated that the AA reaction of the 4-nitrophenyl ether of but-3-en-1-ol granted selective access to either regioisomeric product, providing synthetic access to the unusual amino acids, (3R)-(−)-4-amino-3-hydroxybutyric acid (GABOB) 1 and homoserine 2 in protected form (Scheme 1). In this paper we provide complete experimental details of this work and extend this study to propose an explanation based on substrate-catalyst interactions for the observed changes in AA regioselectivity.

Section snippets

Synthesis of GABOB in protected form

Our initial goal was the synthesis of the unusual amino acid GABOB 1, which has been identified as a key fragment of the microsclerodermins, a family of marine cyclic peptides possessing anti-tumour and anti-fungal activity.8, 8(a), 8(b), 8(c) It is also an agonist of the γ-amino-butyric acid (GABA) receptor and is used in the treatment of epilepsy and hypertension.9

The proposed synthesis required aminohydroxylation of protected but-3-en-1-ol 3ag to give the terminal amine regioisomers 4ag (

Conclusion

In conclusion this work demonstrates that the 4-nitrophenyl ether is an efficient directing group in the asymmetric aminohydroxylation reaction of homoallylic ether derivatives, providing either regioisomeric product with useful levels of enantioselectivity. This finding has been applied to the short enantioselective synthesis of protected GABOB 10 and homoserine 13. The substrate-catalyst interactions responsible for the observed regio- and enantioselectivity of the AA reactions have been

General details

Melting points were determined using a Reichert heating stage with microscope and are uncorrected. Infrared absorption spectra were obtained using a Perkin–Elmer 1600 Fourier Transform Infrared spectrometer as a thin film between 0.5 cm sodium chloride plates. Absorption maxima are expressed in wavenumbers (cm−1) and the appearance of bands are expressed as s=strong, m=medium, w=weak and br=broad. 1H Nuclear magnetic resonance spectra were recorded using a Bruker AC200 (200.1 MHz), Bruker AVANCE

Acknowledgements

Dr. Kelvin Picker, School of Chemistry, University of Sydney, is acknowledged for assistance with HPLC. We thank the Australian Research Council (DP0342590), the Australian National University and The University of Sydney for financial support.

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