Studies on the Base-Catalysed Addition of Amines to Alkynes and Allenes: A Novel Cascade Sequence for the Construction of Spirocyclic Aminals

 

 Buy Article Permissions and Reprints All articles of this category

Abstract

Indoles can be prepared by the intramolecular addition of resin bound amides to allenyl sulfoxides. Amino alkynols have been converted into spirocyclic aminals in one synthetic operation re­presenting an enormous increase in molecular complexity.

References and Notes

• 1 Knight J. Parsons PJ. J. Chem. Soc., Perkin Trans. 1  1987,  1237 
  CrossrefGoogle Scholar
• 2 Lathbury DC. Parsons PJ. Pinto ILS. J. Chem. Soc., Chem. Commun.  1988,  81 
  CrossrefGoogle Scholar
• 3 Parsons PJ. Angell R. Naylor A. Tyrell E. J. Chem. Soc., Chem. Commun.  1993,  366 
  CrossrefGoogle Scholar
• 4 Jenkinson J. Parsons PJ. Eyley SC. Synlett  1993,  679 
  Google Scholar
• 5 Gray M. Parsons PJ. Neary A. Synlett  1993,  281 
  Article in Thieme ConnectGoogle Scholar
• 6a Crowley JI. Rapoport H. J. Am. Chem. Soc.  1970,  92:  6363 
  Article in Thieme ConnectGoogle Scholar
• 6b Crowley JI. Rapoport H. Acc. Chem. Res.  1976,  9:  135 
  Article in Thieme ConnectGoogle Scholar
• 6c Zikos CC. Ferderigos NG. Tetrahedron Lett.  1995,  36:  3741 
  Article in Thieme ConnectGoogle Scholar
• 6d Ajayaghosh A. Pillai VNR. Tetrahedron Lett.  1995,  36:  777 
  Article in Thieme ConnectGoogle Scholar
• 6e Meutermans WDF. Alewood PF. Tetrahedron Lett.  1995,  36:  7709 
  Article in Thieme ConnectGoogle Scholar
• 6f Yu KL. Deshpande MS. Vyas D. Tetrahedron Lett.  1994,  35:  8919 
  Article in Thieme ConnectGoogle Scholar
• 6g Deshpande MS. Tetrahedron Lett.  1994,  35:  5613 
  Article in Thieme ConnectGoogle Scholar
• 6h Frenette R. Friesen RW. Tetrahedron Lett.  1994,  35:  9177 
  Article in Thieme ConnectGoogle Scholar
• 6i Ritter H. Sperber R. Macromolecules  1994,  27:  5919 
  Article in Thieme ConnectGoogle Scholar
• 6j Beebe X. Schore NE. Kurth MJ. J. Am. Chem. Soc.  1992,  114:  10061 
  Article in Thieme ConnectGoogle Scholar
• 6k Beebe X. Schore NE. Kurth MJ. J. Org. Chem.  1995,  60:  4196 
  Article in Thieme ConnectGoogle Scholar
• 6l Ley SV. Mynett DM. Koot W.-J. Synlett  1995,  1017 
  Article in Thieme ConnectGoogle Scholar
• 7 Zhang H.-C. Ye H. Moretto AF. Brumfield KK. Maryanoff BE. Org. Lett.  2000,  89 
  CrossrefGoogle Scholar
• 9 Beer RJS. Donavanik T. Robertsen A. J. Chem. Soc.  1954,  4139 
  Google Scholar
• 10 Kershaw JW. Taylor A. J. Chem. Soc.  1964,  4320 
  Google Scholar
• 11 Berti G. Settimo AD. Colo GD. Nanniperi E. J. Chem. Soc. C  1969,  2703 
  CrossrefGoogle Scholar
• 12 Dave V. Warnhoff EW. Can. J. Chem.  1976,  54:  1015 ; and references cited therein
  Google Scholar
• 13 McLean S. Donitrienko GI. Can. J. Chem.  1971,  49:  3642 
  Google Scholar
• 14 Li J. Marks TJ. J. Am. Chem. Soc.  1996,  118:  9259 ; and references cited therein
  Google Scholar
• 15 Jacobi PA. Brielmann HL. Hauck SI. J. Org. Chem.  1996,  61:  5013 
  CrossrefGoogle Scholar
• 16 Jacobi PA. Liu H. J. Am. Chem. Soc.  1999,  121:  1958 
  CrossrefGoogle Scholar

Typical Experimental Procedure for 3a,4,8b-Tetra-hydro-3′,3a,8b-trimethylspiro{2 H -furo[3,2b]indole-2,2′-indoline}-3′-ol.
A mixture of N-[2-(1-hydroxy-1-methylprop-2-ynyl)phen-yl]acetamide (1, 406 mg, 2 mmol) in MeOH (60 mL), K₂CO₃ (1.104 g, 8 mmol) and H₂O (4 mL) was heated under reflux for 3 h. After removal of MeOH under reduced pressure the residue was taken up in CH₂Cl₂ (5 mL) and the solution was washed with H₂O (5 × 30 mL). The combined organic layers were dried over MgSO₄ and concentrated under reduced pressure. The reaction solution was concentrated and subsequently re-dissolved in CH₂Cl₂. Removal of the solvent under reduced pressure and subsequent dissolution in CH₂Cl₂ was repeated five times until the analysis showed complete conversion of the intermediate. The crude product was purified by column chromatography on silica gel with a mixture of Et₂O and PE (1:1) as the eluent to give 534 mg (83%) of,3a,4,8b-tetrahydro-3′,3a,8b-trimethylspiro{2H-furo[3,2b]indole-2,2′-indoline}-3′-ol (9) as a white solid.
Analytical data: ¹ H NMR (300 MHz, acetone-d ₆): δ = 7.13-7.03 (3 H, m, ArH), 6.85 (1 H, m, ArH), 6.55-6.68 (3 H, m, ArH), 6.32 (1 H, d, ArH, J = 7.7 Hz), 5.41 (1 H, br s, NH), 5.35 (1 H, br s, NH), 3.49 (1 H, s, OH), 2.41 (2 H, s, CH₂, H-10), 1.46 (3 H, s, CH₃), 1.26 (6 H, s, 2 × CH₃). ¹³C NMR (75 MHz, CDCl₃): δ = 149.30 (q, ArC), 147.09 (q, ArC), 134.48 (q, ArC), 131.60 (q, ArC), 130.25 (ArCH), 128.84 (ArCH), 124.72 (ArCH), 123.01 (ArCH), 119.78 (ArCH), 119.67 (ArCH), 110.78 (ArCH), 110.06 (ArCH), 106.16 (q), 91.99 (q), 79.02 (q), 74.59 (q), 42.43 (CH₂, C-1), 24.56 (CH₃, C-14), 22.25 (CH₃, C-8), 20.16 (CH₃, C-13). IR (KBr disc): ν_max = 3502 (s, O-H), 3389 (s), 3347 (s, N-H), 3026 (m), 3042 (m), 3074 (m, ArC-H), 2976 (s), 2959 (m), 2932 (m), 2875 (m, C-H), 1611 (s, ArC=C), 1480 (s), 1461 (s, CH₃ def.), 766 (s), 753 (s, ArC-H bend., o-disubst.). MS (EI): m/z (%) = 322 (62)[M⁺], 177 (14), 158 (33), 145 (100), 91 (16), 65 (9), 43 (20). HRMS (MH⁺): m/z calcd for C₂₀H₂₃N₂O₂: 323.1754; found: 323.1760. R _f (TLC, silica) = 0.39 (Et₂O-PE, 1:1); mp 211 °C (Lit.¹¹ 222-224 °C).