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.

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

References and Notes

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For recent Diels-Alder approaches to functionalized aminocyclohexenes, see:

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<A NAME="RT02701SS-11">11</A> 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 

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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).

<A NAME="RT02701SS-15">15</A> Compounds of this type have recently been used to synthesise 2-iodoanilines: Hegde SG. Kassim AM. Kennedy AI. Tetrahedron  2001,  57:  1689 

<A NAME="RT02701SS-16">16</A> Danishefsky D. Kitahara T. Schuda PF. Org. Synth.  1983,  61:  147