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Synlett 2004(13): 2311-2314  
DOI: 10.1055/s-2004-832804
LETTER
© Georg Thieme Verlag Stuttgart · New York

Hg(II) Reagent-Controlled Stereoselective Synthesis of 2,5-cis- and 2,5-trans-Polyhydroxylated Pyrrolidines

Dinesh Chikkanna, Hyunsoo Han*
Department of Chemistry, The University of Texas at San Antonio, 6900 N. Loop 1604 West, San Antonio, TX 78249, USA
Fax: +1(210)4584958; e-Mail: hhan@utsa.edu;
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Publication History

Received 18 July 2004
Publication Date:
03 September 2004 (online)

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Abstract

Stereoselectivity in the intramolecular amidomercuration reaction of 11, which could form 2,5-cis- and 2,5-trans-polyhydroxylated pyrrolidines, was found to be dependent on the nature of the Hg(II) salts used as well as on the stereochemistry and protection state of the hydroxyl group at the allylic carbon. Thus, the amidomercuration reaction of 11 with Hg(CF3CO2)2 led to the predominant formation of the 2,5-cis-polyhydroxylated pyrrolidine 16, while use of Hg(CF3SO3)2 generated the corresponding 2,5-trans isomer 17. Isomers 16 and 17 were further elaborated to stereoselectively synthesize 2,5-dideoxy 2,5-imino-d-altritol and 2,5-dideoxy 2,5-imino-d-galactitol (for 20 and 21), which are known to be potent d-galactosidase inhibitors.

Key words

carbohydrate - glycosidase inhibitor - polyhydroxylated pyrrolidine - regioselective asymmetric aminohydroxylation reaction - intramolecular amidomercuration reaction

6

The compound I was prepared from the reaction of ethyl 4-bromocrotonate with p-methoxyphenol in the presence of K2CO3 and a catalytic amount of 18-crown-6 in MeCN at r.t. (yield: 80%).

13

Compound 14: [α]D +20.0 (c 1.0, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 7.35-7.25 (5 H, m), 6.82-6.75 (4 H, m), 4.77-4.64 (1 H, m), 4.60-4.55 (2 H, m), 4.25 and 3.84 (1 H, br s), 4.20-4.02 (5 H, m), 3.75 (3 H, s), 2.30 and 2.11 (1 H, m,) 1.59 and 1.30 (1 H, t, J = 10.5 Hz), 1.44 and 1.40 (9 H, s). 13C NMR (125 MHz, CDCl3): δ = 154.0, 153.9, 152.8, 137.4, 128.6, 128.2, 127.8, 115.9, 114.6, 81.3, 80.9, 73.4, 71.6, 65.4, 56.7, 55.6, 55.3, 30.3, 28.4, minor peaks due to rotational isomer(s): 81.0, 80.4, 73.7, 71.6, 70.8, 65.4, 64.1, 58.9, 54.6. Compound 16: [α]D +50.0 (c 1.0, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 7.35-7.28 (5 H, m), 6.93 (2 H, d, J = 9.0 Hz), 6.83 (2 H, d, J = 9.0 Hz), 4.71 (1 H, d, J = 11.5 Hz), 4.67 (1 H, d, J = 11.5 Hz), 4.25-4.12 (6 H, m), 3.78-3.70 (1 H, m), 3.77 (3 H, s), 2.25 (1 H, dd, J = 11.5 and 6.0 Hz), 2.17 (1 H, dd, J = 11.5 and 4.5 Hz), 1.48 (9 H, s). 13C NMR (125 MHz, CDCl3): δ = 155.1, 154.5, 151.9, 137.3, 128.5, 128.1, 127.9, 116.2, 114.7, 81.2, 77.1, 72.6, 70.9, 66.7, 60.1, 59.1, 55.7, 34.0, 28.5. Compound 17: [α]D +19.0 (c 1.0, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 7.40-7.20 (5 H, m), 6.85-6.70 (4 H, m), 4.72 (1 H, d, J = 11.5 Hz), 4.51 (1 H, d, J = 11.5 Hz), 4.50-4.35 (2 H, m), 4.25-4.10 (3 H, m), 4.00 (1 H, br s), 3.71 (3 H, s), 1.91 (1 H, d, J = 12.0 Hz), 1.48 (1 H, d, J = 12.0 Hz), 1.32 (9 H, s). 13C NMR (75 MHz, CDCl3): δ = 154.8, 154.1, 152.0, 137.3, 128.5, 128.0, 127.7, 116.8, 114.6, 81.6, 75.9, 75.8, 71.4, 65.5, 65.4, 58.3, 55.6, 35.0, 28.4.