Palladium-Catalysed Cyclisation
of α-Hydroxy Allylic Acetates: A Formal Synthesis of (±)-Swainsonine

Roderick W. Bates; Mark R. Dewey; Chi H. Tang; Shahidah bte Safii; Yanhan Hong; Jolyn Ke Hui Hsieh; Pei Shan Siah

doi:10.1055/s-0030-1260952

LETTER

Palladium-Catalysed Cyclisation of α-Hydroxy Allylic Acetates: A Formal Synthesis of (±)-Swainsonine

Roderick W. Bates*, Mark R. Dewey, Chi H. Tang, Shahidah bte Safii, Yanhan Hong, Jolyn Ke Hui Hsieh, Pei Shan Siah
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 637371, Singapore, Singapore
Fax: +6567911961; e-Mail: roderick@ntu.edu.sg;

Abstract

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Abstract

A hydroxy group in the allylic position directed the stereochemistry of cyclisation of allylic acetates to form nitrogen heterocycles, giving the trans isomer for the piperidine and the cis isomer for the pyrrolidine. A formal synthesis of (±)-swainsonine was achieved.

Key words

piperidine - palladium - pyrrolidine - alkaloid - cyclisation

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References

References and Notes

<A NAME="RD12711ST-1">1</A> Bates RW. Dewey MR. Org. Lett. 2009, 11: 3706

<A NAME="RD12711ST-2">2</A> Bates RW. Ng PS. Tetrahedron Lett. 2011, 52: 2696

<A NAME="RD12711ST-3">3</A> Hyland C. Tetrahedron 2005, 61: 3457

For reviews of swainsonine synthesis, see:

<A NAME="RD12711ST-4A">4a</A> El Nemr A. Tetrahedron 2000, 56: 8579

<A NAME="RD12711ST-4B">4b</A> Pyne SG. Curr. Org. Synth. 2005, 2: 39

For a recent synthesis, see:

<A NAME="RD12711ST-4C">4c</A> Kwon HY. Park CM. Lee SB. Youn JH. Kang SH. Chem. Eur. J. 2008, 14: 1023

<A NAME="RD12711ST-5">5</A> Washenfelder A. Bussmann DA. Grubbs RH. J. Am. Chem. Soc. 2000, 122: 58

<A NAME="RD12711ST-6">6</A> Fukuyama T. Jow C.-K. Cheung M. Tetrahedron Lett. 1995, 36: 6373

A solution of allylic acetate 9 (389 mg, 1.05 mmol), tetrakis(triphenylphosphine)palladium(0) (60 mg, 5 mol%), and tetramethyl guanidine (131 µL, 1.05 mmol) in THF (5 mL) under nitrogen was stirred at r.t. for 4 h. The mixture was then concentrated in vacuo, and the residue was purified by flash chromatography (silica gel, 30% EtOAc-hexane) to give piperidine 10 (mixture of isomers) as a colourless oil. Major isomer: ^¹H NMR (400 MHz, CDCl₃): δ = 8.12-8.05 (1 H, m), 7.71-7.62 (3 H, m), 5.75 (1 H, ddd, J = 17, 11, 5 Hz), 5.24 (1 H, ddd, J = 11, 2, 1 Hz), 5.23 (1 H, ddd, J = 17, 2, 1 Hz), 4.51 (1 H, m), 3.95 (1 H, m), 3.83 (1 H, br d, J = 13 Hz), 3.24 (1 H, dt, J = 13, 3 Hz), 1.98-1.85 (1 H, m), 1.78-1.63 (2 H, m), 1.49 (1 H, m). ^¹³C NMR (100 MHz, CDCl₃): δ = 148.0, 133.7, 133.4, 132.0, 131.8, 131.1, 124.3, 124.1, 118.9, 67.5, 61.6, 41.9, 25.6, 19.0.

The corresponding t-Boc and aloc-protected substrates failed to cyclise under these conditions.

<A NAME="RD12711ST-9">9</A> Lindsay KB. Pyne SG. J. Org. Chem. 2002, 67: 7774

<A NAME="RD12711ST-10">10</A> Buschmann N. Rückert A. Blechert S. J. Org. Chem. 2002, 67: 4325

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<A NAME="RD12711ST-12">12</A> Poon KWC. Dudley G. J. Org. Chem. 2006, 71: 3923

Details have been deposited with the Cambridge Crystallographic Database, CCDC 819544, and may be obtained at http://www.ccdc.cam.ac.uk.

<A NAME="RD12711ST-14">14</A> Bates RW. Lu Y. Org. Lett. 2010, 12: 3938 ; and references therein

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<A NAME="RD12711ST-15B">15b</A> Thaning M. Wistrand LG. J. Org. Chem. 1990, 55: 1406

<A NAME="RD12711ST-15C">15c</A> Carretero JC. Arrayás RG. de Cracia IS. Tetrahedron Lett. 1996, 37: 3379

Details have been deposited with the Cambridge Crystallographic Database, CCDC 819546, and may be obtained at http://www.ccdc.cam.ac.uk.