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

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.

Key words

cascade - amine - alkyne - allene sulfoxide - combinatorial chemistry - spirocyclic

References and Notes

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

8

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).