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DOI: 10.1055/s-0031-1290342
Unactivated Norbornenes in [3+2] Cycloadditions: Remarkably Stereo-controlled Entry into Norbornane-Fused Spirooxindolopyrrolidines, Spiro-1,3-indandionolylpyrrolidines, and Spirooxindolopyrrolizidines
Publikationsverlauf
Publikationsdatum:
08. Februar 2012 (online)
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Abstract
1,3-dipolar cycloaddition reactions of azomethine ylides with unactivated norbornene dipolarophiles and a highly diastereoselective synthesis of the novel norbornane-fused spirooxindolopyrrolidines, spiroacenaphthylenolylpyrrolidines, spiro-1,3-indan-dionolylpyrrolidines, and spirooxindolopyrrolizidines having an array of stereocenters are reported. The stereoselective synthesis of spirooxindolopyrrolizidines with eight stereocenters was demonstrated. Single-crystal X-ray structural analyses were performed to unambiguously establish the structure and stereochemistry of the key products.
Key words
1,3-dipolar cycloaddition - oxindoles - spiro compounds - stereoselective synthesis - ylides
- Supporting Information for this article is available online:
- Supporting Information
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References and Notes
Crystallographic data of all X-ray
crystal structures reported in this work have been deposited with
the Cambridge Crystallographic Data Centre under the following deposition numbers:
CCDC 847073 (13), CCDC 847074 (14), CCDC 847075 (22),
CCDC 847076 (30a), CCDC 847077 (31a), CCDC 847078 (33),
CCDC 847079 (34), CCDC 847080 (36), CCDC 847081 (37),
CCDC 847082 (43), and CCDC 847083 (46b).
Typical
Experimental Procedure
A dry flask containing N-methylisatin (5a,
161 mg, 1 mmol), sarcosine (6, 98 mg, 1.1
mmol), and the norbornene dipolarophile 7a (213
mg, 1 mmol) in EtOH (3 mL) was heated at 80 ˚C
for 20 h under an inert atmosphere. After completion of the reaction
(TLC monitoring), the flask containing the reaction mixture was
cooled to r.t., and the solvent was evaporated under vacuum. Purification
of the resulting crude reaction mixture by column chromatography on
neutral alumina (EtOAc-hexanes = 60:40)
gave the product 13 (220 mg, 55%).
Spectral Data for Compound 13
Colorless
solid; mp 223-225 ˚C (MeOH-hexanes = 1:1).
IR (KBr): 2948, 2906, 1750, 1717, 1606, 1467, 1437 cm-¹. ¹H NMR
(400 MHz, CDCl3): δ = 7.56 (d, 1 H, J = 7.6 Hz),
7.34 (t, 1 H, J = 7.6
Hz), 7.11 (t, 1 H, J = 7.6
Hz), 6.85 (d, 1 H, J = 7.6
Hz), 4.88 (s, 1 H), 4.56 (s, 1 H), 3.68 (s, 3 H), 3.60 (s, 3 H),
3.47 (t, 1 H, J = 8.2
Hz), 3.20 (s, 3 H), 3.08 (d, 1 H, J = 9.6
Hz), 3.01-2.98 (m, 1 H), 2.87 (d, 1 H, J = 9.6
Hz), 2.89-2.85 (m, 1 H), 2.65 (d, 1 H, J = 8.2
Hz), 1.96 (s, 3 H). ¹³C NMR (100 MHz,
CDCl3): δ = 178.2, 171.1, 144.0, 129.4, 127.8,
126.1, 122.7, 108.3, 82.1, 80.4, 74.2, 58.4, 55.8, 52.2, 52.1, 51.5,
50.7, 47.5, 35.1, 26.3. MS (CI): m/z (%) = 402 (100) [M + 2]+,
401 (30) [M + 1]+ 195
(8), 175 (7), 111 (30), 79 (15). ESI-HRMS: m/z calcd
for C21H24N2O6Na [M + Na]+:
423.1532; found: 423.1532 [M + Na]+.