Synthesis of 4-Aminocyclohex-1-enecarboxylates from Danishefsky’s Diene

Abstract

An efficient BF₃·Et₂O mediated conversion of Diels-Alder adduct 1 of Danishefsky’s diene and methyl acrylate yielded cyclohexenones 2 and 3. Subsequent reductive amination with several amines using NaBH(OAc)₃ in acetic acid medium gave 4-alkylaminocyclohex-1-enecarboxylate derivatives (4a-e) in a concise form.

Key words

aminations - Diels-Alder reactions - enones - reductions - Danishefsky’s diene

References and Notes

• 1 Quirante J. Escolano C. Massot M. Bonjoch J. Tetrahedron  1997,  53:  1391 
• For recent Diels-Alder approaches to functionalized aminocyclohexenes, see:
• 2a Huang Y. Iwama T. Rawal VH. J. Am. Chem. Soc.  2000,  122:  7843 , and references cited therein
• 2b Wipf P. Wang X. Tetrahedron Lett.  2000,  41:  8747 
• 3a Danishefsky S. Kitahara T. J. Org. Chem.  1975,  40:  538 
• 3b Danishefsky S. Kitahara T. Yan CF. Morris J. J. Am. Chem. Soc.  1979,  101:  6996 
• 4a Archer RA. Blanchard WB. Day WA. Johnson DW. Lavagnino ER. Ryan CW. Baldwin JE. J. Org. Chem.  1977,  42:  2277 
• 4b Lemmens JM. Thijs L. Zwanenburg B. Tetrahedron  1984,  40:  3331 
• 4c Moore BS. Cho H. Casati R. Kennedy E. Reynolds KA. Mocek U. Beale JM. Floss HG. J. Am. Chem. Soc.  1993,  115:  5254 
• 5 Jung ME. Rayle HL. Synth. Commun.  1994,  24:  197 
• 6 Spino C. Crawford J. Cui Y. Gugelchuk M. J. Chem. Soc., Perkin Trans. 2  1998,  1499 
• 7a Carter MJ. Fleming I. Percival A. J. Chem. Soc., Perkin Trans. 1  1981,  2415 
• 7b Kosugi H. Hoshino K. Uda H. Chem. Lett.  1991,  1577 
• 8 Potman RP. Janssen NJML. Scheeren JW. Nivard RJF. J. Org. Chem.  1984,  49:  3628 
• 9 Audrain H. Skrydstrup T. Ulibarri G. Riche C. Chiaroni A. Grierson DS. Tetrahedron  1994,  50:  1469 
• 10 It is assumed that methanol is eliminated concurrently with the cleavage of the silyl enol ether to the ketone.3b For an interesting study in this field, see: Vorndam PE. J. Org. Chem.  1990,  55:  3693 
• 11 Conversion of the carboxylic Diels-Alder adducts of Danishefsky’s diene to cyclohexenones has been recently reported using acid catalysts such as Yb(OTf)₃, although upon some substrates amounts of the corresponding methoxylated derivatives were also obtained: Inokuchi T. Okano M. Miyamoto T. Madon HB. Takagi M. Synlett  2000,  1549 
• 12 Abdel-Magid AF. Carson KG. Harris BD. Maryanoff CA. Shah RD. J. Org. Chem.  1996,  61:  3849 
• 13 McGill JM. Labell ES. Williams M. Tetrahedron Lett.  1996,  37:  3977 
• 15 Compounds of this type have recently been used to synthesise 2-iodoanilines: Hegde SG. Kassim AM. Kennedy AI. Tetrahedron  2001,  57:  1689 
• 16 Danishefsky D. Kitahara T. Schuda PF. Org. Synth.  1983,  61:  147 

14

¹H NMR (CDCl₃, 300 MHz): δ = 1.09-1.28 (m, 2 H, H-2_ax, H-6_ax), 1.46 (qd, 2 H, J = 13, 3.5 Hz, H-3_ax, H-5_ax), 2.02 (m, 4 H, H-3, H-5), 2.28 (tt, 1 H, J = 12, 3.5 Hz, H-1), 2.51 (tt, 1 H, J = 11, 3.5 Hz, H-4), 3.66 (s, 3 H, OCH₃), 3.82 (s, 2 H, CH₂Ar), 7.20-7.40 (m, 5 H, Ar-H); ¹³C NMR (CDCl₃, 75 MHz): δ = 27.7 (C-6, C-2), 32.3 (C-5, C-3), 42.9 (C-1), 51.0 (CH₂Ar), 51.6 (OCH₃), 55.5 (C-4), 126.9, 128.1, 128.4, 140.2 (Ar), 176.2 (CO).