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Synlett 2003(13): 1989-1992  
DOI: 10.1055/s-2003-42055
LETTER
© Georg Thieme Verlag Stuttgart · New York

Tin Triflate Catalysed Selective Synthesis of N,N′-Unsymmetrically Substituted N-(Hydroxyclovanyl)-N′-aryl Acetamidines

Antonio J. Macías-Sánchez, Carlos F. D. Amigo, Isidro G. Collado*
Departamento de Química Orgánica, Facultad de Ciencias,, Universidad de Cádiz, Apartado 40, 11510 Puerto Real, Cádiz, Spain
Fax: +34(95)6016193; e-Mail: isidro.gonzalez@uca.es;
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Publication History

Received 24 June 2003
Publication Date:
08 October 2003 (online)

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Abstract

The unsymmetrically substituted amidines 6a-d have been prepared in one step from caryophyllene oxide (2), aromatic amines (4a-c, 5), and tin triflate as catalyst, in refluxing MeCN.

Key words

natural products - cyclization - epoxides - Lewis acids - amidines

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Typical Experimental Procedure: To a magnetically stirred solution of caryophyllene oxide (2) (450 mg, 2.045 mmol) and aniline (4a) (353 mg, 8.18 mmol) in anhyd MeCN (8 mL), Sn(OTf)2 (351 mg, 0.51 mmol) was added and the reaction mixture was heated to 80 °C. After 24 h., once compound 2 was consumed (TLC), the solvent was evaporated under reduced pressure and the crude reaction mixture was purified by column chromatography on silica gel to yield the amidine 6a (340 mg, 47%) and the amine 7a (36 mg, 5%).

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Selected physical data for compound 6a: [α]D +16.6 (c 9.2 mg/mL, MeOH). Selected physical and spectroscopic data for compound 6b: [α]D -3.2 (c 43.3 mg/mL, MeOH). 1H NMR (400 MHz, CD3OD): δ = 0.86 (s, 3 H, H3-15′), 0.89 (s, 3 H, H3-13′α), 1.01 (s, 3 H, H3-14′β), 1.20 (d, J 12 ′ a-12 ′ b = 11.0 Hz, 1 H, H-12′a), 1.42 (d, J 12 ′ b-12 ′ a = 11.0 Hz, 1 H, H-12′b), 1.62 (dd, J 3 ′ α - 2 ′ α = 6.6 Hz, J 3 ′ α - 3 ′ β = 11.4 Hz, 1 H, H-3′α), 1.70 (t, J 3 ′ β - 2 ′ α = J 3 ′ β - 3 ′ α = 11.4 Hz, 1 H, H-3′β), 1.94 (m, 1 H, H-10′b), 2.04 (s, 3 H, H3-2), 3.16 (br s, 1 H, H-9′β), 3.72 (s, 3 H, H3-1′′′), 4.04 (dd, J 2 ′ α -3 ′ β = 11.40 Hz, J 2 ′ α -3 ′ α = 6.6 Hz, 1 H, H-2′α), 6.92 (d, J 3 ′′ - 2 ′′ = J 5 ′′ - 6 ′′ = 9.0 Hz, 2 H, H-3′′, H-5′′), 7.19 (d, J 2 ′′ - 3 ′′ = J 6 ′′ - 5 ′′ = 9.0 Hz, 2 H, H-2′′, H-6′′). 13C NMR (100 MHz, CD3OD): δ = 18.60 (c, C-2), 21.56 (t, C-6′), 24.62 (c, C-13′), 26.54 (t, C-10′), 28.79 (t, C-11′), 29.01 (c, C-15′), 30.91 (c, C-14′), 33.92 (t, C-7′), 36.01 (s, C-8′), 36.62 (t, C-12′), 39.07 (s, C-4′), 45.29 (t, C-3′), 47.03 (s, C-1′), 51.91 (d, C-5′), 56.07 (c, C-1′′′), 61.97 (d, C-2′), 75.13 (d, C-9′), 115.92 (2C, d, C-3′′, C-5′′), 128.65 (s, C-1′′), 129.50 (2C, d, C-2′′, C-6′′), 161.34 (s, C-4′′), 165.71 (s, C-1). MS (EI): m/z (rel. int.) = 384 (87) [M+], 369 (22) [M - 15]+, 325 (41), 262 (33). Compound 6c: [α]D +12.9 (c 20 mg/mL, MeOH). 1H NMR (400 MHz, CD3OD): δ 0.92 (s, 3 H, H3-15′), 0.94 (s, 3 H, H3-13′α), 1.05 (s, 3 H, H3-14′β), 1.74 (m, 1 H, H-12′b), 1.77 (s, 3 H, H3-2), 2.00 (m, 1 H, H-10′b), 3.22 (br s, 1 H, H-9′β), 4.29 (m, 1 H, H-2′α), 6.70 (d, J 2 ′′ -3 ′′ = J 6 ′′ -5 ′′ = 8.4 Hz, 2 H, H-2′′, H-6′′), 7.33 (d, J 3 ′′ -2 ′′ = J 5 ′′ - 6 ′′ = 8.4 Hz, 2 H, H-3′′, H-5′′). 13C NMR (100 MHz, CD3OD): δ = 18.08 (c, C-2), 21.76 (t, C-6′), 25.02 (c, C-13′), 26.79 (t, C-10′), 29.04 (t, C-11′), 29.18 (c, C-15′), 31.31 (c, C-14′), 34.46 (t, C-7′), 35.93 (s, C-8′), 37.19 (t, C-12′), 38.40 (s, C-4′), 45.74 (t, C-3′), 46.68 (s, C-1′), 52.11 (d, C-5′), 59.40 (d, C-2′), 75.78 (d, C-9′), 115.64 (s, C-4′′), 126.18 (d, 2 C, C-2′′, C-6′′), 132.63 (d, C-3′′, C-5′′), 152.51 (s, C-1′′), 159.51 (s, C-1). MS (EI): m/z (rel. int.) = 434(48) [M + 2]+, 432 (47) (M+), 375 (23), 373 (22), 353 (41) [M - 79]+, 292 (27), 262(46). Compound 6d: [α]D +98.4 (c = 17 mg/mL, MeOH). 1H NMR (400 MHz, CD3OD): δ = 0.96 (s, 3 H, H3-15′), 1.00 (s, 3 H, H3-13′), 1.14 (s, 3 H, H3-14′), 1.86 (2 H, H-3′α, H-3′α), 2.08 (m, 1 H, H-10′b), 2.59 (m, 3 H, H3-2), 3.25 (sa, 1 H, H-9′β), 4.02 (dd, J 2 ′ α -3 ′ β = 11.1 Hz, J 2 ′ α -3 ′ α = 6.3 Hz, 1 H, H-2′α), 7.40 (t, J 4 ′′ -3 ′′ = J 4 ′′ - 5 ′′ = 5.0 Hz, 1 H, H-4′′), 8.81 (d, J 3 ′′ - 4 ′′ = J 5 ′′ - 4 ′′ = 5.0 Hz, 2 H, H-3′′, H-5′′). 13C NMR (100 MHz, CD3OD): δ = 17.81 (c, C-2), 21.60 (t, C-6′), 24.77 (c, C-13′), 26.64 (t, C-10′), 28.89 (c, C-15′), 29.01 (t, C-11′), 30.91 (c, C-14′), 33.83 (t, C-7′), 36.03 (s, C-8′), 36.46 (t, C-12′), 39.49 (s, C-4′), 46.34 (t, C-3′), 46.61 (s, C-1′), 51.87 (d, C-5′), 65.85 (d, C-2′), 75.14 (d, C-9′), 119.82 (d, C-4′′), 159.16 (s, C-1′′), 159.69 (d, 2 C, C-3′′, C-5′′), 165.96 (s, C-1). HMBC cross peaks (selected): C-1 → H-2′α, H3-2. MS (EI): m/z (rel. int.) = 357 (27) [M + 1]+, 339 (40) [M + 1 - 18]+, 263(24)

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Selected physical and spectroscopic data for compound 8: [α]D +14.0 (c 2.2 mg/mL, MeOH). 1H NMR (400 MHz, CDCl3): δ = 0.92 (s, 3 H, H3-13′α), 0.95 (s, 3 H, H3-15′), 1.06 (s, 3 H, H3-14′β), 1.66 (dd, J = 10.8, 11.6 Hz, 1 H, H-3′β), 1.76 (m, 1 H, H-11′b), 1.77 (s, 3 H, H3-2), 2.00 (m, 1 H, H-10′b), 3.24 (s, 3 H, H3-1′′′), 3.31 (br s,1 H, H-9′β), 3.46 (dd, J = 6.0, 10.8 Hz, 1 H, H-2′α), 7.08 (d, J = 7.6 Hz, 2 H, H-2′′, H-6′′), 7.17 (t, J = 7.6 Hz, 1 H, H-4′′), 7.32 (d, J = 7.6 Hz, 2 H, H-3′′, H-5′′). 13C NMR (75 MHz, CDCl3): δ = 15.06 (q, C-2), 21.02 (t, C-6′), 25.51 (q, C-13′α), 26.45 (t, C-10′), 28.12 (t, C-11′), 28.50 (q, C-15′), 31.38 (q, C-14′β), 33.45 (t, C-7′), 34.95 (s, C-8′*), 36.76 (t, C-12′), 38.62 (s, C-1′*), 39.67 (q, C-1′′′), 46.09 (s, C-4′*), 47.46 (t, C-3′), 50.75 (d, C-5′), 67.55 (d, C-2′), 75.41 (d, C-9′), 125.41 (d, C-4′′), 126.75 (d, 2 C, C-2′′, C-6′′), 129.15 (d, 2 C, C-3′′, C-5′′), 147.17 (s, C-1′′), 156.02 (s, C-1). HMBC cross peaks(selected): C-1 → H3-1′′′, H-2′α, H3-2; C-1′′ → H3-1′′′, H-3′′, H-5′′. MS (EI): m/z (rel. int.) = 368 [M]+(10), 353 [M - 15]+(5), 262 (20).