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Synlett 2007(4): 0559-0562  
DOI: 10.1055/s-2007-970743
LETTER
© Georg Thieme Verlag Stuttgart · New York

Rh(II)-Catalyzed Intramolecular N-H Insertion of d-Glucose-Derived δ-Amino α-Diazo β-Ketoester: Synthesis of Pyrrolidine Iminosugars

Vinod P. Vyavaharea, Subrata Chattopadhyayb, Vedavati G. Puranikc, Dilip D. Dhavale*a
a Garware Research Centre, Department of Chemistry, University of Pune, Pune 411007, India
b Bio-Organic Division, Bhaba Atomic Research Centre, Mumbai 400085, India
c Center for Materials Characterization, National Chemical Laboratory, Pune 411008, India
Fax: +91(20)25691728; e-Mail: ddd@chem.unipune.ernet.in;
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Publication History

Received 3 November 2006
Publication Date:
21 February 2007 (online)

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Abstract

The rhodium acetate catalyzed reaction of d-glucose-derived δ-amino α-diazo β-ketoester allows a stereoselective β-facial intramolecular N-H insertion reaction that leads to formation of the bicyclic pyrrolidinone ring skeleton in high yield. The sugar-sub­stituted pyrrolidinone thus obtained was elaborated to allow the synthesis of promising glycosidase inhibitors, namely, 2,5-dideoxy-2,5-imino-l-glycero-α-d-galactoheptitol and 2,5-dideoxy-2,5-imino-d-galactitol.

Key words

alkaloids - azasugars - carbohydrates - pyrrolidines - rhodium carbenoid - N-H insertion

19

The synthesis of α-d-ribopentodialdose is known, however that of α-d-xylopentodialdose is unknown.

20

The formation of 10 as a major product in 94% yield could be explained on the basis of the hydride delivery in LiAlH4, reducing from the convex face; the concave face attack of hydride afforded the corresponding C-5 epimeric compound in 6% yield as a minor product as evident from the 1H and 13C NMR spectral data.

21

Perbenzylation at room temperature under a variety of reaction conditions for prolonged time afforded a mixture of mono-, di- and tribenzylated products.

22

The NaBH4 (2.5 equiv) reduction of an anomeric mixture of hemiacetal was sluggish and led to only 50% conversion into the corresponding alcohol. Use of an excess amount of NaBH4 did not improve the yield of the product.

24

All new compounds have been characterized by 1H NMR, 13C NMR, IR, and elemental analysis. Ethyl-3,6-dideoxy-3-benzyloxycarbonylamino-1,2- O -isopropylidene-α- d -xylohept-5-ulofuranuronate ( 7): viscous liquid; R f 0.65 (n-hexane-EtOAc, 5:1); [α]D +3.33 (c = 0.60, CHCl3). IR (neat): 3150-3400(br), 1730, 1650 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.26 (t, J = 7.4 Hz, 3 H), 1.30 (s, 3 H), 1.50 (s, 3 H), 3.40 (d, J = 16.0 Hz, 1 H), 3.75 (d, J = 16.0 Hz, 1 H), 4.18 (q, J = 7.4 Hz, 2 H), 4.50-4.62 (br m, 2 H), 4.89 (d, J = 3.3 Hz, 1 H), 5.08 (AB quartet, J = 12.0 Hz, 2 H), 5.86 (d, J = 3.6 Hz, 1 H), 5.89 (d, J = 3.3 Hz, 1 H), 7.20-7.40 (br s, 5 H). 13C NMR (75 MHz, CDCl3): δ = 14.0, 26.1, 26.7, 46.8, 58.0, 61.7, 66.9, 83.5, 84.3, 104.7, 112.5, 127.8, 127.9, 128.3, 128.4, 135.9, 155.5, 167.3, 199.4. The 1H and 13C NMR spectrum showed additional signals (<5%) corresponding to the enol form of the β-ketoester. Anal. Calcd for C20H25NO8 (407.41): C, 58.96; H, 6.18. Found: C, 58.82; H, 6.12.
Ethyl-3,6-dideoxy-6-diazo-3-benzyloxycarbonylamino-1,2- O -isopropylidene-α- d -xylohept-5-ulofuranuronate ( 8): yield: 87%; viscous liquid; R f 0.60 (n-hexane-EtOAc, 5:1); [α]D +44.00 (c = 0.5, CHCl3). IR (neat): 3150-3330, 2146, 1716, 1658 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.38 (t, J = 6.9 Hz, 3 H), 1.35 (s, 3 H), 1.59 (s, 3 H), 4.32 (q, J = 6.9 Hz, 2 H), 4.57 (d, J = 3.3 Hz, 1 H), 4.67 [(dd, J = 3.6, 8.7 Hz, 1 H); on D2O exchange became (d, J = 3.6 Hz)], 5.05 (s, 2 H), 5.22 (br d, J = 8.7 Hz, 1 H, exchanges with D2O), 5.69 (d, J = 3.6 Hz, 1 H), 5.97 (d, J = 3.3 Hz, 1 H), 7.20-7.40 (m, 5 H). 13C NMR (75 MHz, CDCl3): δ = 14.6, 26.6, 27.1, 58.3, 62.4, 67.2, 80.0, 84.8, 104.6, 112.8, 128.1, 128.3, 128.7, 136.2, 155.6, 160.5, 186.1. In the 13C NMR the C5 carbon did not appear due to the presence of C=N2. This is analogous to the earlier observation reported by Davis. [2] Anal. Calcd for C20H23N3O8 (433.15): C, 55.42; H, 5.35. Found: C, 55.32; H, 5.32.
Preparation of Ethyl-3,6-dideoxy-3,6-benzyloxy-carbonylamino-1,2- O -isopropylidine-α- d -xylohept-5-ulofuranuronate ( 9): To the solution of the diazo com-pound 8 (1.00 g, 2.30 mmol) in anhyd benzene (5 mL) was added Rh2(OAc)4 (0.03g, 0.04 mmol) under nitrogen atmosphere and the solution was refluxed for 20 min. On cooling, the reaction mixture was directly loaded on a silica gel column and eluted (n-hexane-EtOAc, 7:3) to give 9 as a viscous liquid (0.73 g, 78%); R f 0.50 (n-hexane-EtOAc, 3:2); [α]D +10.00 (c = 0.8, CHCl3). IR (neat): 3150-3421 (br), 1750, 1660 cm-1. Anal. Calcd for C20H23NO8 (405):
C, 59.25; H, 5.72. Found: C, 59.27; H, 5.68. The 1H and 13C NMR spectra of this compound showed complex patterns due to keto-enol tautomerism and doubling of signals associated with the NCbz functionality.
3,6-Dideoxy-3,6-( N -benzylamino)-5,7-di- O -benzyl-1,2- O -isopropylidene-α- d -glycero-d-glucohepto-1,4-furanose ( 10): yield: 68%; white solid; mp 96-97 °C; R f 0.70 (n-hexane-EtOAc, 19:1); [α]D +48.57 (c = 0.7, CHCl3). IR (KBr): 1452, 1369, 1124, 1074, 698 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.23 (s, 3 H), 1.45 (s, 3 H), 3.21 (ddd, app q, J = 5.7, 6.3, 6.6 Hz, 1 H), 3.39 (d, J = 5.4 Hz, 1 H), 3.55 (dd, J = 6.3, 9.3 Hz, 1 H), 3.80 (dd, J = 5.7, 9.3 Hz, 1 H), 3.83 (d, J = 14.0 Hz, 1 H), 3.93 (dd, J = 4.8, 6.6 Hz, 1 H), 4.00 (d, J = 14.0 Hz, 1 H), 4.15 (d, J = 3.6 Hz, 1 H), 4.45 (AB q, J = 12.0 Hz, 2 H), 4.53 (d, J = 12.0 Hz, 1 H), 4.75 (d, J = 12.0 Hz, 1 H), 4.78 (dd, J = 4.8, 5.4 Hz, 1 H), 5.85 (d, J = 3.6 Hz, 1 H), 7.20-7.40 (m, 15 H). 13C NMR (75 MHz, CDCl3): δ = 26.6, 27.5, 57.7, 65.0, 70.8, 71.3, 72.7, 73.2, 78.0, 82.3, 84.8, 107.2, 112.0, 127.0, 127.3, 127.5, 127.7, 128.1, 129.2, 137.7, 138.0, 138.3. Anal. Calcd for C31H35NO5 (501.61): C, 74.23; H, 7.03. Found: C, 74.22; H, 7.00.
2,5-Dideoxy-2,5-imino-1,3-di- O -benzyl-l-glycero-α- d -galactoheptitol ( 11): yield: 81%; viscous liquid; R f 0.40 (n-hexane-EtOAc, 9:1); [α]D +3.07 (c = 0.65, CHCl3). IR (neat): 3100-3550, 1639, 1456, 1369 cm-1. 1H NMR (300 MHz, CDCl3 + D2O): δ = 3.02-3.12 (m, 2 H, H-3), 3.16 (ddd, J = 2.1, 4.2, 8.1 Hz, 1 H), 3.36 (dd, J = 2.7, 9.3 Hz, 1 H), 3.58 (d, J = 13.5 Hz, 1 H), 3.66 (dd, J = 4.5, 11.4 Hz, 1 H), 3.77 (dd, J = 4.5, 11.4 Hz, 1 H), 3.96 (ddd, app q, J = 4.5, 4.8, 9.6 Hz, 1 H), 4.01 (d, J = 13.5 Hz, 1 H), 4.05 (dd, J = 4.8, 8.1 Hz, 1 H), 4.22 (dd, J = 4.8, 5.1 Hz, 1 H), 4.44 (AB q, J = 12.0 Hz, 2 H), 4.45 (d, J = 11.7 Hz, 1 H), 4.68 (d, J = 11.7 Hz, 1 H), 7.20-7.40 (m, 15 H). 13C NMR (75 MHz, CDCl3 + D2O): δ = 60.3, 63.3, 64.8, 67.1, 68.4, 69.4, 69.9, 71.9, 73.5, 77.7, 127.2, 127.5, 127.6, 127.7, 128.3, 129.7, 137.0, 137.7, 138.5. Anal. Calcd for C28H33NO5 (463.57): C, 72.55; H, 7.18. Found: C, 72.49; H, 7.15.
2,5-Dideoxy-2,5-imino-l-glycero-α- d -galactoheptitol ( 12): yield: 85%; viscous liquid; R f 0.10 (MeOH);
[α]D -86.66 (c = 0.6, H2O). IR (nujol): 3200-3600(br) cm-1. 1H NMR (300 MHz, D2O): δ = 3.27 (dd, J = 5.7, 6.0 Hz, 1 H), 3.46 (ddd, app q, J = 5.8, 6.4, 6.6 Hz, 1 H), 3.63 (dd, J = 6.6, 12.0 Hz, 1 H), 3.72-3.78 (m, 2 H, H-7b), 3.83 (dd, J = 5.1, 11.4 Hz, 1 H), 3.97 (ddd, J = 3.3, 6.3, 9.9 Hz, 1 H), 4.29 (dd, J = 4.8, 5.7 Hz, 1 H), 4.35 (dd, J = 4.8, 6.6 Hz, 1 H). 13C NMR (75 MHz, D2O): δ = 62.1, 62.3, 62.4, 65.8, 71.9, 73.7, 73.7. Anal. Calcd for C7H15NO5 (193.2): C, 43.52; H, 7.83. Found: C, 43.50; H, 7.81.
2,5-Dideoxy-2,5-imino- d -galactitol ( 14): yield: 83%; viscous liquid; R f 0.10 (MeOH). IR (nujol): 3200-3600(br) cm-1. 1H NMR (300 MHz, D2O): δ = 3.75-3.83 (m, 2 H, H-2), 3.92 (dd, J = 8.4, 12.3 Hz, 2 H), 4.01 (dd, J = 5.1, 12.3 Hz, 2 H) 4.50 (dd, J = 1.5, 4.5 Hz, 2 H). 13C NMR (75 MHz, D2O): δ = 60.2, 63.8, 72.3. Anal. Calcd for C6H13NO4 (163): C, 44.16; H, 8.03. Found: C, 44.17; H, 8.05.
2,5-Dideoxy-2,5-imino- d -galactitol Hydrochloride ( 15): yield: 89%; semi solid. IR (nujol): 3200-3600(br) cm-1. 1H NMR (300 MHz, D2O): δ = 3.73-3.81 (m, 2 H), 3.90 (dd, J = 8.1, 12.0 Hz, 2 H), 4.01 (dd, J = 4.8, 12.0 Hz, 2 H), 4.48 (d, J = 5.1 Hz, 2 H). 13C NMR (75 MHz, D2O): δ = 57.8, 61.4, 70.0. Anal. Calcd for C6H14NO4Cl (199.5): C, 36.10; H, 7.07. Found: C, 36.12; H, 7.07.