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

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

References and Notes

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• 2 Bates RW. Ng PS. Tetrahedron Lett.  2011,  52:  2696 
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• For reviews of swainsonine synthesis, see:
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• 4b Pyne SG. Curr. Org. Synth.  2005,  2:  39 
• For a recent synthesis, see:
• 4c Kwon HY. Park CM. Lee SB. Youn JH. Kang SH. Chem. Eur. J.  2008,  14:  1023 
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7

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.

8

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

13

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

16

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