Elsevier

Tetrahedron Letters

Volume 51, Issue 1, 6 January 2010, Pages 60-63
Tetrahedron Letters

Synthesis of new β- and γ-aminopyrrolidinephosphonates via 1,3-dipolar cycloaddition of substituted vinylphosphonates

https://doi.org/10.1016/j.tetlet.2009.10.087Get rights and content

Abstract

Synthesis of α- and β-(aminomethyl)vinylphosphonates was achieved from vinyl bromide via a cross-coupling reaction with triethyl phosphite and by cross-metathesis of allyl bromide and vinylphosphonate, respectively. The 1,3-dipolar cycloaddition of these vinylphosphonates with a dipole in the presence of trifluoroacetic acid afforded selectively the β-aminopyrrolidinephosphonates. Syntheses of cis- and trans-γ-aminopyrrolidinephosphonates are also described.

Introduction

Vinylphosphonates have been known for several decades1 and constitute a very important class of building blocks for the synthesis of complex structures,2 including biologically active molecules.3 The β-aminovinylphosphonates, although rarely described,4 have been used for the synthesis of β-aminophosphonic acid derivatives5 that display interesting biological properties such as antibiotics,6 enzyme inhibitors,7and anti-HIV agents.8 However, synthesis of heterocyclic β-aminophosphonates, in particular pyrrolidine analogues, remains a challenge.

Syntheses of substituted pyrrolidines are largely reported by cycloaddition of a 1,3-dipole with vinyl derivatives.9 To the best of our knowledge, only one 1,3-dipolar cycloaddition reaction has been reported between a 1,3-dipole and an unsubstituted vinylphosphonate to provide a heterocyclopentylphosphonate.10 On the contrary, the 1,3-dipolar cycloaddition reaction with substituted vinylphosphonate is still unknown.

In continuation of our work on the development of new methodology for the synthesis of heterocyclic aminophosphonic acids,11 and considering the importance of heterocyclic aminophosphonates in synthetic, agrochemical, and medicinal chemistry,12 we decided to investigate the 1,3-dipolar cycloaddition of α- and β-substituted vinylphosphonates with azomethine ylides to access a range of pyrrolidines, for phosphonopeptide construction (Fig. 1).

In this Letter, we report the synthesis of the first members of a new class of β- and γ-aminophosphoryl pyrrolidines.

Section snippets

Results and discussion

Synthesis of β-aminovinylphosphonates 1 was achieved by the SN2 displacement of the allylic bromide 2 by oxazolidinone or amide 3 in the presence of a base (Cs2CO3 or NaH). Then, vinyl bromide 4 was coupled with triethyl phosphite at 150 °C in the presence of a catalytic amount of nickel bromide.13 The resulting vinylphosphonates 1 were obtained in good yields (Scheme 1, Table 1).14

It is noteworthy that the preparation of 1b from oxazolidinone (±)-3b by chloromethylation [(CH2O)n/TMSCl] to

Conclusion

In summary, an easy and efficient synthesis of new β- and γ-aminopyrrolidinephosphonates involving a 1,3-dipolar cycloaddition of the corresponding vinyl phosphonates with a dipole in the presence of TFA has been described. Furthermore, new synthetic routes to vinylphosphonates have been developed via a cross-coupling reaction of vinyl bromide with triethyl phosphite to afford α-(amino-methyl)vinylphosphonates and via a cross-metathesis to provide a trans-β-(aminomethyl) analogue, in good

Acknowledgments

The authors thank Mr. M. Decoux and R. Blareau for technical assistance and Dr. Jason Martin for proofreading the manuscript.

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