Cyclohepta[de]naphthalenes and the Rearranged Abietane Framework of Microstegiol via Nicholas Reaction Chemistry

Abstract

Nicholas reactions on 2,7-dioxygenated naphthalenes give C-1 monosubstitution and C-1/C-8 disubstitution in most ­cases. From γ-carbonyl cation monocondensation product 3b or alkyne-unsubstituted dicondensation product 4a, cyclohepta[de]naphthalenes bearing no substituents, gem-dimethyl substituents, and a ketone function, and the rearranged abietane framework of microstegiol may be prepared.

Key words

carbocations - alkyne complexes - transition metals - electrophilic aromatic substitution - ring closure - tautomerism

References and Notes

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• 1b Patel MM. Green JR. Chem. Commun.  1999,  509 
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• 1d Green JR. Synlett  2001,  353 
• 1e Ding Y. Green JR. Synlett  2005,  271 
• 1f Djurdjevic S. Green JR. Org. Lett.  2007,  9:  5505 
• For recent reviews on the Nicholas reaction, see:
• 2a Diaz DD. Betancort JM. Martin VS. Synlett  2007,  343 
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• For γ-carbonyl cation equivalents by way of iron allyl cations, see:
• 4a Green JR. Carroll MK. Tetrahedron Lett.  1991,  32:  1141 
• 4b Zhou T. Green JR. Tetrahedron Lett.  1993,  34:  4497 
• 4c Charlton MA. Green JR. Can. J. Chem.  1997,  75:  965 
• 4d Enders D. Jandeleit B. Von Berg S. Synlett  1997,  421 ; and references therein
• For γ-carbonyl cation equivalents by way of π-allyl-palladium complexes, see:
• 5a Nemoto T. Fukuda T. Matsumoto T. Hitomi T. Hamada Y. Adv. Synth. Catal.  2005,  347:  1504 
• 5b Nemoto T. Fukuda T. Hamada Y. Tetrahedron Lett.  2006,  47:  4365 ; and references therein
• For γ-carbonyl cation equivalents by way of carbonyl-substituted cyclopropanes, see:
• 6a Lifchits O. Alberico D. Zakharian I. Charette AB. J. Org. Chem.  2008,  73:  6838 ; and references therein
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13

To a solution of 2,7-dimethoxynaphthalene(1) in CH₂Cl₂ (0.05 M) at 0 ˚C was added propargyl alcohol complex 2 (1.1 equiv for monocondensations, 2.2 equiv for dicondensations) and BF₃˙OEt₂ (3 equiv). After 3 h of stirring at 0 ˚C, aq NH₄Cl was added, and the mixture subjected to a conventional extractive workup. Purification by flash chromatography afforded 3 (monocondensation) or 4 and 5 (dicondensation).

14

Analytical Data for Selected Compounds Compound 3a: IR (KBr): ν_max = 3003, 2960, 2090, 2055
cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 7.71 (d, J = 8.9 Hz, 1 H), 7.70 (d, J = 8.9 Hz, 1 H), 7.22 (d, J = 2.4 Hz, 1 H), 7.10 (d, J = 8.9 Hz, 1 H), 7.04 (dd, J = 8.9, 2.4 Hz, 1 H), 5.95 (s, 1 H), 4.60 (s, 2 H), 3.97 (s, 3 H), 3.94 (s, 3 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 199.6, 158.4, 154.7, 133.9, 130.2, 128.6, 124.6, 120.1, 116.1, 109.7, 101.6, 96.1, 73.5, 55.4, 55.1, 29.5. MS: m/e = 484 [M⁺ - CO], 456 [M⁺ - 2 CO], 428 [M⁺ - 3 CO], 372 [M⁺ - 5 CO]. HRMS: m/e calcd for C₂₁H₁₄Co₂O₈ [M⁺ - 2 CO]: 455.9454; found: 455.9441.
Compound 3b: IR (KBr): ν_max = 3003, 2951, 2097, 2063, 2028, 1708 cm^-¹. ^¹H NMR (500 MHz, CDCl₃ ): δ = 7.72 (d, J = 8.9 Hz, 1 H), 7.68 (d, J = 8.9 Hz, 1 H), 7.18 (d, J = 2.3 Hz, 1 H), 7.10 (d, J = 8.9 Hz, 1 H), 7.02 (dd, J = 8.9, 2.3 Hz, 1 H), 4.64 (s, 2 H), 3.96 (s, 3 H), 3.95 (s, 3 H), 3.53 (s, 3 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 198.4, 171.7, 158.5, 154.7, 133.9, 130.1, 128.8, 124.4, 119.1, 116.2, 109.3, 101.1, 99.4, 79.3, 55.2, 54.9, 52.4, 29.0. MS: m/e = 570 [M⁺], 542 [M⁺ - 1 CO], 514 [M⁺ -2 CO], 486 [M⁺ - 3 CO], 458 [M⁺ - 4 CO], 430 [M⁺ - 5 CO], 402 [M⁺ - 6 CO]. HRMS: m/e calcd for C₂₃H₁₆Co₂O₁₀ [M⁺ - CO]: 541.9458; found: 541.9455.

15

However, substitution at the propargylic site in 2 resulted in condensation reactions at C-3 in preference to C-1.

16

Analytical Data for Selected Compounds Compound 4a: IR (KBr): ν_max = 2917, 2090, 2051, 2021
cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 7.70 (d, J = 8.9 Hz, 2 H), 7.12 (d, J = 8.9 Hz, 2 H), 5.83 (s, 2 H), 5.22 (d, J = 16.4 Hz, 2 H), 4.50 (d, J = 16.4 Hz, 2 H), 3.99 (s, 6 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 199.6, 156.1, 131.9, 130.7, 126.5, 121.3, 110.1, 97.5, 73.8, 55.9, 30.6. MS: m/e = 808 [M⁺ - 1 CO], 780 [M⁺ - 2 CO], 752 [M⁺ - 3 CO], 724 [M⁺ - 4 CO], 696 [M⁺ - 5 CO], 668 [M⁺ - 6 CO], 640 [M⁺ - 7 CO], 612 [M⁺ - 8 CO]. HRMS: m/e calcd for C₃₀H₁₆Co₄O₁₄ [M⁺ - CO]: 807.7917; found: 807.7904.
Compound 4b: IR (KBr): ν_max = 3004, 2950, 2097, 2067, 1710 cm^-¹. ^¹H NMR (500 MHz, CDCl₃ ): δ = 7.71 (d, J = 9.0 Hz, 2 H), 7.10 (d, J = 9.0 Hz, 2 H), 5.19 (d, J = 16.5 Hz, 2 H), 4.69 (d, J = 16.5 Hz, 2 H), 3.40 (s, 6 H), 3.46 (s, 6 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 198.2, 170.6, 156.1, 132.1, 131.0, 126.3, 120.3, 109.8, 99.9, 80.3, 55.7, 52.4, 30.9. MS: m/e = 896 [M⁺ - 2 CO], 840 [M⁺ - 4 CO], 784 [M⁺ -6 CO], 728 [M⁺ - 8 CO], 700 [M⁺ - 9 CO].

17

Compound 6: IR (KBr): ν_max = 3291, 2932, 2107, 1618
cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 7.72 (d, J = 9.0 Hz, 2 H), 7.18 (d, J = 9.0 Hz, 2 H), 4.31 (d, J = 2.6 Hz, 4 H), 4.03 (s, 6 H), 2.16 (t, J = 2.6 Hz, 2 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 156.7, 133.5, 130.1, 126.2, 117.3, 111.0, 84.7, 69.1, 56.9, 17.3. MS: m/e = 264 [M⁺]. HRMS: m/e calcd for C₁₈H₁₆O₂ [M⁺] = 264.1150; found: 264.1153.
Compound 7: IR (KBr): ν_max = 3077, 2934, 1614 cm^-¹. ^¹H NMR (300 MHz, CDCl₃ ): δ = 7.72 (d, J = 8.9 Hz, 2 H), 7.18 (d, J = 8.9 Hz, 2 H), 6.23 (m, 2 H), 5.09 (dd J = 10.3, 1.9 Hz, 2 H), 4.84 (dd, J = 17.3, 1.9 Hz, 2 H), 3.93 (s, 6 H), 3.91 (m, 4 H). ^¹³C NMR (75 MHz, CDCl₃ ): δ = 156.7, 139.0, 134.9, 129.4, 126.3, 120.4, 114.5, 111.0, 56.8, 30.9. MS: m/e = 268 [M⁺]. HRMS: m/e calcd for C₁₈H₂₀O₂ [M⁺]: 268.1463; found: 268.1466.
Compound 8: IR (KBr): ν_max = 3033, 2934, 1616 cm^-¹. ^¹H NMR (500 MHz, CDCl₃ ): δ = 7.59 (d, J = 9.0 Hz, 2 H), 7.11 (d, J = 9.0 Hz, 2 H), 6.19 (m, 2 H), 4.02 (d, J = 5.6 Hz, 4 H), 3.92 (s, 6 H). ^¹³C NMR (125 MHz, CDCl₃ ): δ = 153.9, 134.8, 130.9, 128.3, 126.8, 120.2, 111.9, 57.2, 24.2. MS: m/e = 240 [M⁺]. HRMS: m/e calcd for C₁₆H₁₆O₂ [M⁺]: 240.1150; found: 240.1150.

19

Analytical Data for Selected Compounds Compound 10: IR (KBr): ν_max = 2956, 2233, 1712, 1628
cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 7.72 (d, J = 9.0 Hz, 1 H), 7.69 (d, J = 8.9 Hz, 1 H), 7.22 (d, J = 2.4 Hz, 1 H), 7.11 (d, J = 9.0 Hz, 1 H), 7.05 (dd, J = 8.9, 2.4 Hz, 1 H), 4.11 (s, 2 H), 3.97 (s, 3 H), 3.96 (s, 3 H), 3.70 (s, 3 H). ^¹³C NMR (125 MHz, CDCl₃ ): δ = 158.4, 154.6, 154.0, 133.7, 129.9, 128.9, 124.3, 116.1, 113.6, 110.1, 101.2, 87.7, 71.9, 56.1, 55.0, 52.2, 14.5. MS: m/e = 284 [M⁺]. HRMS: m/e calcd for C₁₇H₁₆O₄ [M⁺]: 284.1049; found: 284.1033.
Compound 11: IR (KBr): ν_max = 2954, 1740, 1628 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 7.69 (d, J = 8.9 Hz, 1 H), 7.66 (d, J = 8.9 Hz, 1 H), 7.32 (d, J = 2.0 Hz, 1 H), 7.12 (d, J = 8.9 Hz, 1 H), 7.03 (dd, J = 8.9, 2.0 Hz, 1 H), 3.98 (s, 3 H), 3.93 (s, 3 H), 3.70 (s, 3 H), 3.11 (t, J = 7.6 Hz, 2 H), 2.44 (t, J = 7.1 Hz, 2 H), 2.00 (m, 2 H). ^¹³C NMR (75 MHz, CDCl₃ ): δ = 174.0, 158.1, 154.8, 134.1, 129.8, 127.3, 124.5, 121.2, 115.7, 110.2, 101.6, 55.9, 55.1, 51.2, 33.4, 24.2, 24.1. MS: m/e = 288 [M⁺]. HRMS: m/e calcd for C₁₇H₂₀O₄ [M⁺]: 288.1362; found: 288.1360.
Compound 13: IR (KBr): ν_max = 3422 (br), 2966, 1627 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 7.70 (d, J = 8.9 Hz, 1 H), 7.66 (d, J = 8.9 Hz, 1 H), 7.24 (d, J = 2.3 Hz, 1 H), 7.13 (d, J = 8.9 Hz, 1 H), 7.05 (dd, J = 8.9, 2.3 Hz, 1 H), 3.952 (s, 3 H), 3.945 (s, 3 H), 3.09 (t, J = 7.6 Hz, 2 H), 1.75 (m, 2 H), 1.69 (m, 2 H) 1.38 (br s, 1 H), 1.23 (s, 6 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 158.0, 154.8, 134.1, 130.0, 127.1, 124.7, 122.6, 115.5, 110.8, 102.0, 70.9, 56.3, 55.1, 43.8, 29.1, 25.4, 24.4. MS: m/e = 288 [M⁺]. HRMS: m/e calcd for C₁₈H₂₄O₃ [M⁺]: 288.1725; found: 288.1713.
Compound 9: IR (KBr): ν_max = 2929, 1612 cm^-¹. ^¹H NMR (500 MHz, CDCl₃ ): δ = 7.54 (d, J = 8.9 Hz, 1 H), 7.52 (d, J = 8.8 Hz, 1 H), 7.09 (d, J = 8.9 Hz, 1 H), 7.07 (d, J = 8.8 Hz, 1 H), 3.95 (s, 3 H), 3.92 (s, 3 H), 3.00 (br m, 2 H), 1.96 (m, 2 H), 1.70 (m, 2 H), 1.52 (s, 6 H). ^¹³C NMR (125 MHz, CDCl₃ ): δ = 158.8, 154.5, 137.6, 131.7, 127.3, 126.9, 125.4, 122.9, 112.1, 111.6, 84.6, 57.4, 56.0, 41.1, 39.4, 25.5, 22.1. MS: m/e = 270 [M⁺]. HRMS: m/e calcd for C₁₈H₂₂O₂ [M⁺]: 270.1620; found: 270.1614.

20

Analytical Data for Selected Compounds Compound 17: IR (KBr): ν_max = 3004, 2952, 2099, 2063, 2029,1765, 1709 cm^-¹. ^¹H NMR (500 MHz, CDCl₃ ): δ = 7.82 (d, J = 9.0 Hz, 1 H), 7.81 (d, J = 8.8 Hz, 1 H) 7.61 (d, J = 2.2 Hz, 1 H), 7.26 (d, J = 9.0 Hz, 1 H), 7.11 (dd, J = 8.8, 2.2 Hz, 1 H), 4.60 (s, 2 H), 3.96 (s, 3 H), 3.75 (s, 3 H), 2.33 (s, 3 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 198.0, 170.5, 169.4, 154.7, 149.3, 133.2, 130.0, 128.8, 126.8, 120.0, 118.6, 114.1, 111.8, 98.5, 93.9, 55.2, 52.5, 28.2, 20.8. MS: m/e = 542 [M⁺ - 2 CO], 514 [M⁺ - 3 CO], 486 [M⁺ - 4 CO], 458 [M⁺ - 5 CO], 430 [M⁺ - 6 CO]. HRMS: m/e calcd for C₂₄H₁₆Co₂O₁₁ [M⁺ - 3 CO]: 513.9509; found: 513.9511.
Compound 18: IR (KBr). ν_max = 2917, 2234, 1761, 1712 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 7.81 (d, J = 8.9 Hz, 2 H), 7.62 (d, J = 2.1 Hz, 1 H), 7.26 (d, J = 8.9 Hz, 1 H), 7.15 (dd. J = 8.8, 2.1 Hz, 1 H), 4.08 (s, 2 H), 3.99 (s, 3 H), 3.71 (s, 3 H), 2.38 (s, 3 H). ^¹³C NMR (75 MHz, CDCl₃ ): δ = 169.4, 154.7, 154.0, 149.4, 133.1, 129.9, 129.2, 126.9, 118.8, 114.8, 113.7, 112.7, 87.4, 72.0, 56.3, 52.3, 21.0, 14.6. MS: m/e = 312 [M⁺]. HRMS: m/e calcd for C₁₈H₁₆O₅ [M⁺]: 312.0998; found: 312.0991.
Compound 19: IR (KBr): ν_max 3067, 2950, 1759, 1734 cm^-¹. ^¹H NMR (500 MHz, CDCl₃ ): δ = 7.75 (d, J = 8.8 Hz, 1 H), 7.67 (d, J = 1.9 Hz, 1 H), 7.65 (d, J = 9.0 Hz, 1 H), 7.16 (d, J = 9.0 Hz, 1 H), 7.09 (dd, J = 8.8, 1.9 Hz, 1 H), 3.85 (s, 3 H), 3.64 (s, 3 H), 3.08 (t, J = 17.6 Hz, 2 H), 2.39 (t, J = 7.4 Hz, 2 H), 2.33 (s, 3 H), 1.99 (m, 2 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 173.9, 169.5, 154.9, 149.1, 133.6, 129.9, 127.6, 127.1, 122.3, 118.4, 114.0, 112.7, 56.1, 51.2, 33.5, 24.7, 24.0, 21.1. MS: m/e = 316 [M⁺]. HRMS: m/e calcd for C₁₈H₂₀O₅ [M⁺]: 316.1311; found: 316.1316.
Compound 20: IR (KBr): ν_max = 3385 (br), 2924, 1703, 1626 cm^-¹. ^¹H NMR (500 MHz, acetone-d ₆): δ = 7.63 (d, J = 8.8 Hz, 1 H), 7.62 (d, J = 9.0 Hz, 1 H), 7.28 (br s, 1 H), 7.11 (d, J = 9.0 Hz, 1 H), 6.93 (dd, J = 8.8, 2.1 Hz, 1 H), 3.87 (s, 3 H), 2.99 (t, J = 7.7 Hz, 2 H), 2.35 (m, 2 H), 1.85 (m, 2 H). ^¹³C NMR (125 MHz, acetone-d ₆): δ = 174.5, 156.0, 155.1, 134.8, 130.2, 127.7, 124.5, 120.7, 115.7, 110.3, 104.8, 55.8, 33.3, 24.8, 24.1. MS: m/e = 260 [M⁺]. HRMS: m/e calcd for C₁₅H₁₆O₄ [M⁺]: 260.1049; found: 260.1045.
Compound 15: IR (KBr): ν_max = 3009, 2970, 1616 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 12.73 (s, 1 H), 7.71 (d, J = 8.9 Hz, 1 H), 7.63 (d, J = 8.8 Hz, 1 H), 7.12 (d, J = 8.8 Hz, 1 H), 6.93 (d, J = 8.9 Hz, 1 H), 3.95 (s, 3 H), 3.01 (t, J = 7.1 Hz, 2 H), 2.71 (t, J = 7.4 Hz, 2 H), 2.39 (m, 2 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 207.4, 162.5, 157.3, 136.2, 135.7, 128.6, 123.2, 122.3, 116.5, 115.2, 110.3, 56.2, 42.3, 29.5, 25.4. MS: m/e = 242 [M⁺]. HRMS: m/e calcd for C₁₅H₁₄O₃ [M⁺]: 242.0943; found: 242.0931.

22

Analytical Data for Selected Compounds Compound 21: IR (KBr): ν_max = 3358, 2967 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 8.10 (br s, 1 H), 7.65 (d, J = 8.8 Hz, 1 H), 7.61 (d, J = 8.9 Hz, 1 H), 7.33 (d, J = 2.2 Hz, 1 H), 7.08 (d, J = 8.9 Hz, 1 H), 7.01 (dd, J = 8.8, 2.2 Hz, 1 H), 3.91 (s, 3 H), 2.95 (br t, J = 7.0 Hz, 2 H), 2.60 (br s, 1 H), 1.65 (m,
4 H), 1.21 (s, 6 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 154.6, 154.5, 134.4, 130.3, 127.3, 124.5, 122.1, 115.6, 110.7, 105.3, 72.0, 56.4, 43.5, 29.1, 25.4, 24.3. MS: m/e = 274 [M⁺]. HRMS: m/e calcd for C₁₇H₂₂O₃: 274.1569; found: 274.1574.
Compound 22: IR (KBr): ν_max = 2934, 1653, 1615 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 7.29 (d, J = 9.7 Hz, 1 H), 7.13 (d, J = 8.4 Hz, 1 H), 6.79 (d, J = 8.4 Hz, 1 H), 5.97 (d, J = 9.7 Hz, 1 H), 3.84 (s, 3 H), 3.63 (s, 1 H), 3.36 (m, 1 H), 2.42 (m, 1 H), 1.84 (m, 1 H), 1.51 (m, 1 H), 1.38 (m, 1 H), 1.27 (m, 1 H), 1.17 (s, 3 H), 0.66 (s, 3 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 203.2, 157.7, 145.5, 140.8, 129.4, 127.9, 124.4, 123.5, 108.9, 58.3, 55.7, 43.2, 37.0, 27.4, 24.2, 21.5, 20.2. MS: m/e 256 [M⁺]. HRMS: m/e calcd for C₁₇H₂₀O₂: 256.1463; found: 256.1457.