New Synthetic Approach to C5-Hydroxymethyl-Substituted Polyhydroxylated Pyrrolizidines

Daniela Beňadiková; Michal Medvecký; Alexandra Filipová; Ján Moncoľ; Milan Gembický; Naďa Prónayová; Robert Fischer

doi:10.1055/s-0033-1339123

Synlett, Table of Contents

Synlett 2014; 25(11): 1616-1620
DOI: 10.1055/s-0033-1339123

letter

New Synthetic Approach to C5-Hydroxymethyl-Substituted Polyhydroxylated Pyrrolizidines

Authors

Daniela Beňadiková

^aInstitute of Organic Chemistry, Catalysis and Petrochemistry, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovak Republic Email: robert.fischer@stuba.sk
Michal Medvecký

^aInstitute of Organic Chemistry, Catalysis and Petrochemistry, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovak Republic Email: robert.fischer@stuba.sk
Alexandra Filipová

^aInstitute of Organic Chemistry, Catalysis and Petrochemistry, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovak Republic Email: robert.fischer@stuba.sk
Ján Moncoľ

^bInstitute of Inorganic Chemistry, Technology and Materials, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovak Republic
Milan Gembický

^cBruker AXS Inc., 5465 East Cheryl Parkway, Madison, WI 53711-5373, USA
Naďa Prónayová

^dInstitute of Analytical Chemistry, Department of NMR Spectroscopy and Mass Spectrometry, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovak Republic
Robert Fischer*

^aInstitute of Organic Chemistry, Catalysis and Petrochemistry, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovak Republic Email: robert.fischer@stuba.sk

Abstract

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Abstract

A new approach to C5-hydroxymethyl-substituted pyrrolizidines involving 1,3-dipolar cycloaddition of a d-mannose-derived cyclic nitrone and the S_N-reaction of a silyl ketene acetal is presented. The synthesis shows good stereoselectivity as a result of the presence of a dioxolane substituent at C5 of the nitrone, the bulkiness of the silyl ketene acetal, and the shape of the pyrrolizidinylium intermediate formed during intramolecular reductive amination. This approach provides access to pyrrolizidines with the same relative configuration as that found in hyacinthacines C₂ and C₃, and in (+)-pochonicine.

Key words

carbohydrates - heterocycles - nitrones - pyrrolizidines - stereoselective synthesis

Full Text

References

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17 Crystallographic Data Collection and Refinement X-ray data were collected on a Bruker Kappa APEX Ultra diffractometer with mirror-monochromated Cu Kα radiation with a rotating anode Nonius FR951 at 100 K. The structure was solved by direct methods using SHELXS-97 [see ref. 20a], refined by a full-matrix least-squares procedure with CRYSTALS [ver. 14.43; see ref. 20b], and drawn with the OLEX2 package [see ref. 20c]. The chirality of carbon atoms was confirmed by using the PLATON program [see ref. 20d] for C1(S), C3(S), C4(R), C5(S), C6(S), and C7(S). X-ray Data for C₁₆H₂₅NO₇ (8a) Monoclinic, space group, P2₁, a = 8.6080(5), b = 9.8526(6), c = 10.6718(6) Å, β = 103.018(2)°, V = 881.83(9) Å³, Z = 2; final R = 0.0255, R _w = 0.0657, S = 1.004, Flack parameter –0.03(12); maximum and minimum residual densities 0.15 and –0.15 eÅ^–3, respectively. Crystallographic data for compound 8a have been deposited with accession number CCDC 883297, and can be obtained free of charge from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44(1223)336033; E-mail: deposit@ccdc.cam.ac.uk; Web site: www.ccdc.cam.ac.uk/conts/retrieving.html.
18 Methyl {(3aS,4S,7S,8aS,8bR)-4-[(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl]-2,2-dimethylhexahydro[1,3]dioxolo[3,4]-pyrrolo[1,2-b]isoxazol-7-yl}(dimethoxy)acetate (9) Colorless oil; yield: 430 mg (69%); [α]_D ²⁰ +59.80 (c 0.99, CHCl₃). ¹H NMR (600 MHz, CDCl₃): δ = 1.29 (s, 6 H, 2 × CH₃), 1.34 (s, 3 H, CH₃), 1.47 (s, 3 H, CH₃), 2.62 (ddd, J = 12.8, 8.9, 1.3 Hz, 1 H, H-3_a), 2.81 (ddd, J = 13.0, 8.3, 5.5 Hz, 1 H, H-3_b), 3.30 (s, 3 H, OCH₃), 3.40 (s, 3 H, OCH₃), 3.77–3.68 (m, 2 H, H-6, H-3a), 3.82 (s, 3 H, OCH₃), 3.96 (d, J = 7.1 Hz, 2 H, H-5′_a,b), 4.24 (td, J = 7.1, 2.8 Hz, 1 H, H-4′), 4.42 (dd, J = 8.9, 5.5 Hz, 1 H, H-2), 4.66 (dd, J = 5.4, 6.1 Hz, 1 H, H-4), 4.82 (dd, J = 6.3, 1.4 Hz, 1 H, H-5). ¹³C NMR (150.1 MHz, CDCl₃): δ = 24.4, 25.0, 26.0, 26.5, 31.0, 50.3, 50.7, 52.9, 66.2, 69.6, 71.7, 76.4, 77.1, 83.1, 86.1, 101.8, 109.5, 112.9, 167.6.
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