An Unexpected Double-Bond Isomerization Catalyzed by Crabtree’s Iridium(I) Catalyst

Abstract

The first iridium-catalyzed isomerization of an exocyclic into an endocyclic double bond is described. A mechanism is proposed for this reaction. Crabtree’s catalyst thus allows the migration of a double bond that does not occur under classical conditions.

iridium - catalysis - isomerization - olefination - aldol-like reaction

References

1 Hoveyda AH. Evans DA. Fu GC. Chem. Rev.  1993,  93:  1307 ; and references therein

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8

Representative Procedures for the Synthesis of 3 and 1.1-(5-Methoxy-1-methyl-2-methylene-1,2,3,4-tetrahydronaphthalen-1-yl)ethanol ( 3).
To a solution of aldehyde 12 (83 mg, 0.38 mmol) in THF was added methyllithium (1.6 N solution in hexane, 0.53 mL, 0.85 mmol) at -78 °C. The solution was stirred at
-78 °C for 2 h. The reaction mixture was quenched with aq sat. NaHCO₃ at -78 °C and extracted with CH₂Cl₂. The combined organic layers were washed with H₂O, brine, and dried (Na₂SO₄), and the solvent was evaporated. Chromatography on preparative TLC (elution with heptane-EtOAc, 85:15) of the residue afforded 3 (77 mg, 87%) as a colorless oil. ¹H NMR (300 MHz, CDCl₃): δ = 7.19 (t, J = 7.9 Hz, 1 H, H7), 6.98 (d, J = 8,0 Hz, 1 H, H6), 6.73 (d, J = 8,0 Hz, 1 H, H8), 5.13 (s, 1 H, 15%, H14α), 5.11 (s, 1 H, 85%, H14α), 5.00 (s, 1 H, 85%, H14β), 4.91 (s, 1 H, 15%, H14β), 4.13 (q, J = 7.1 Hz, 1 H, 15%, H13), 4.06 (quad, J = 6.5 Hz, 1 H, 85%, H13), 3.83 (s, 3 H, H11), 3.10-2.95 (m, 1 H, H4α), 2.69-2.36 (m, 3 H, H4β-H3), 1.48 (s, 3 H, H12), 1.69 (d, J = 6.3 Hz, 3 H, 15%, H15), 1.02 (d, J = 6.4 Hz, 3 H, 85%, H15) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 157.5 (C5), 151.0 (C2), 144.5 (C9), 127.2 (C7), 126.9 (C10), 119.6 (C8), 111.2 (C15), 108.1 (C6), 74.1 (C13), 56.1 (C11), 48.9 (C1), 32.7 (C3), 23.1 (C12), 19.5 (C14) ppm. IR (CHCl₃): ν = 1577, 1461, 1251, 1047 cm^-1. HRMS (ESI): m/z calcd for C₁₅H₂₀O₂: 232.1463; found: 255.1374 [M + Na].
1-(5-Methoxy-1,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)ethanol ( 1). A solution of alcohol 3 (28 mg, 0.12 mmol) in 2 mL of CH₂Cl₂ in a Schlenk apparatus was cooled at -180 °C and degassed under vacuum then filled with argon. Crabtree’s catalyst (10 mg, 0.012 mmol) was added and the solution degassed again under vacuum and filled with argon. The mixture was allowed to warm to r.t. and the Schlenk tube was linked to an hydrogenation apparatus. The system was flushed ten times with hydrogen and stirred 12 h at r.t. under an atmospheric pressure of hydrogen. The solvent was then removed under vacuum and the resulting slurry dissolved in Et₂O and filtered on a short silica pad. Chromatography on preparative TLC (elution with heptane-EtOAc, 85:15) of the residue afforded 1 (26 mg, 92%) as a colorless oil. H NMR (300 MHz, CDCl₃): δ = 7.19 (t, J = 7.9 Hz, 1 H, H7), 6.98 (d, J = 8.0 Hz, 1 H, H6), 6.73 (d, J = 8.0 Hz, 1 H, H8), 5.13 (s, 1 H, 15%, H14α), 5.11 (s, 1 H, 85%, H14α), 5.00 (s, 1 H, 85%, H14β), 4.91 (s, 1 H, 15%, H14β), 4.13 (quad, J = 7.1 Hz, 1 H, 15%, H13), 4.06 (quad, J = 6.5 Hz, 1 H, 85%, H13), 3.83 (s, 3 H, H11), 3.10-2.95 (m, 1 H, H4α), 2.69-2.36 (m, 3 H, H4β-H3), 1.48 (s, 3 H, H12), 1.69 (d, J = 6.3 Hz, 3 H, 15%, H15), 1.02 (d, J = 6.4 Hz, 3 H, H15) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 157.5 (C5), 151.0 (C2), 144.5 (C9), 127.2 (C7), 16.9 (C10), 119.6 (C8), 111.2 (C15), 108.1 (C6), 74.1 (C13), 56.1 (C11), 48.9 (C1), 32.7 (C3), 25.1 (C4), 23.1 (C12), 19.5 (C14) ppm. IR (CHCl₃): ν = 3453, 1579, 1459, 1254, 1062 cm^-1. HRMS (ESI): m/z calcd for C₁₅H₂₂O₂: 234.1620; found: 257.1492 [M + Na].

9

When this reaction was conducted in the same conditions with shorter time (1 h) no isomerization of 3 was observed.

10

Representative Procedures for the Synthesis of 13, 14, 4 and 15.1-(1,4-Dimethoxybutyl)-5-methoxy-1-methyl-3,4-dihydro-1 H -naphthalen-2-one ( 13).
To a solution of 9 (68 mg, 0.26 mmol) in CH₂Cl₂ 580 mL was added 1,1,4-trimethoxybutane (3.8 g, 26.2 mmol) at
-78 °C. The solution was stirred at -78 °C for 10 min then BF₃·OEt₂ (2.94 mL, 23.2 mmol) was added. The reaction mixture was stirred for 6 h at -78 °C. The residue was diluted with CH₂Cl₂ and washed with sat. aq NaHCO₃. The combined organic layers were washed with H₂O, brine, and dried (Na₂SO₄), and the solvent was evaporated. Flash chromatography on silica gel (elution with heptane-EtOAc, 90:10) of the residue afforded 13 (3.63 g, 76%) and 14 (907 mg, 19%) as white solids.
Compound 13: ¹H NMR (300 MHz, CDCl₃): δ = 7.21 (t, J = 8.0 Hz, 1 H, H7), 6.91 (d, J = 8.0 Hz, 1 H, H8), 6.80 (d, J = 8.1 Hz, 1 H, H6), 3.85 (s, 3 H, H11), 3.66 (dd, J = 10.4, 2.2 Hz, 1 H, H13), 3.33-3.15 (m, 3 H, H16-H4α), 3.31 (s, 3 H, H17), 3.17 (s, 3 H, H18), 2.94 (ddd, J = 16.1, 11.8, 5.5 Hz, 1 H, H4β), 2.73 (ddd, J = 16.2, 5.3, 3.3 Hz, 1 H, H3α), 2.44 (ddd, J = 16.2, 11.7, 6.9 Hz, 1 H, H3β), 1.70-1.45 (m, 2 H, H14), 1.43 (s, 3 H, H12), 1.35-1.20 (m, 2 H, H15) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 213.9 (C2), 156.0 (C5), 142.2 (C9), 127.1 (C7), 125.1 (C10), 120.1 (C8), 107.8 (C6), 88.4 (C13), 72.7 (C16), 61.7 (C18), 58.5 (C17), 56.2 (C1), 55.4 (C11), 37.9 (C3), 29.5 (C14), 27.0 (C15), 23.4 (C12), 21.6 (C12) ppm. IR (CHCl₃): ν = 3155, 2985, 2255, 1805, 1794, 1643, 1470, 1382, 1167, 1096, 926 cm^-1. HRMS (ESI): m/z calcd for C₁₈H₂₆O₄: 306.3966; found: 329.1734 [M + Na]. Anal. Calcd for C₁₈H₂₆O₄ (%): C, 69.54; H, 7.30; O, 23.16. Found: C, 69.48; H, 7.37; O, 23.15.
Compound 14: ¹H NMR (300 MHz, CDCl₃): δ = 7.21 (t, J = 8.0 Hz, 1 H, H7), 6.91 (d, J = 8.0 Hz, 1 H, H8), 6.80 (d, J = 8.1 Hz, 1 H, H6), 3.85 (s, 3 H, H11), 3.66 (dd, J = 10.4, 2.2 Hz, 1 H, H13), 3.33-3.15 (m, 3 H, H16, H4α), 3.31 (s, 3 H, H17), 3.17 (s, 3 H, H18), 2.94 (ddd, J = 16.1, 11.8, 5.5 Hz, 1 H, H4β), 2.73 (ddd, J = 16.2, 5.3, 3.3 Hz, 1 H, H3α), 2.44 (ddd, J = 16.2, 11.7, 6.9 Hz, 1 H, H3β), 1.70-1.45 (m, 2 H, H14), 1.43 (s, 3 H, H12), 1.35-1.20 (m, 2 H, H15) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 215.2 (C2), 156.1 (C5), 140.4 (C9), 126.6 (C7), 125.5 (C10), 120.6 (C8), 108.3 (C6), 88.5 (C13), 72.7 (C16), 61.2 (C18), 58.6 (C17), 56.3 (C1), 55.4 (C11), 37.8 (C3), 28.4 (C14), 26.9 (C15), 20.3 (C4), 20.2 (C12) ppm. IR (CHCl₃): ν = 3155, 2984, 2254, 1794, 1706, 1642, 1469, 1382, 1261, 1167, 1096 cm^-1.
1-(1,4-Dimethoxybutyl)-5-methoxy-1-methyl-2-methylene-1,2,3,4-tetrahydronaphthalene ( 4).
To a solution of ketone 12 (3.3 g, 10.7 mmol) in THF were successively added at r.t. methyltriphenylphosphonium bromide (19.1g, 54 mmol) and potassium tert-butoxide (6 g, 54 mmol). The reaction mixture was stirred at r.t. for 48 h. The reaction mixture was diluted with Et₂O and washed with sat. aq NaHCO₃. The combined organic layers were washed with H₂O, brine, and dried (Na₂SO₄), and the solvent was evaporated. Flash chromatography on silica gel (elution with heptane-EtOAc, 90:10) of the residue afforded 4 (3.17g, 97%) as a white solid. ¹H NMR (300 MHz, CDCl₃): δ = 7.22-7.15 (m, 2 H, H7, H8), 6.69 (dd, J = 7.3, 1.8 Hz, 1 H, H6), 5.03 (q, J = 1.3 Hz, 1 H, H19α), 4.85 (d, J = 1.3 Hz, 1 H, H19β), 3.82 (s, 3 H, H11), 3.39 (dd, J = 10.2, 2.0 Hz, 1 H, H13), 3.34 (t, J = 6.7 Hz, 2 H, H16), 3.31 (s, 3 H, H18), 3.17 (s, 3 H, H18), 2.95-2.80 (m, 1 H, H4α), 2.80-2.55 (m, 2 H, H3α, H4β), 2.50-2.40 (m, 1 H, H3β), 1.85-1.70 (m, 2 H, H15), 1.44 (s, 3 H, H12), 1.35-1.15 (m, 2 H, H14) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 156.3 (C5), 151.8 (C2), 143.6 (C9), 127.2 (C10), 125.9 (C7), 119.9 (C8), 109.1 (C9), 107.0 (C6), 90.8 (C13), 73.0 (C16), 61.5 (C18), 58.5 (C17), 55.4 (C11), 48.1 (C1), 32.7 (C3), 28.2 (C14), 27.2 (C15), 26.2 (C12), 24.6 (C4) ppm. Anal. Calcd for C₁₉H₂₈O₃ (%): C, 74.96; H, 9.27; O, 15.77. Found: C, 74.75; H, 9.09; O, 16.01. IR (CHCl₃): ν = 1577, 1461, 1433, 1367, 1254, 1047 cm^-1. HRMS (ESI): m/z calcd for C₁₉H₂₈O₃: 304.2038; found: 327.1894 [M + Na].
1-(1,4-Dimethoxybutyl)-5-methoxy-1,2-dimethyl-1,4-dihydronaphthalene ( 15).
A solution of alkene 4 (98 mg, 0.32 mmol) in 3 mL of CH₂Cl₂ in a Schlenk apparatus was cooled at -180 °C and degassed under vacuum then filled with argon. Crabtree’s catalyst (11 mg, 0.012 mmol) was added and the solution degassed again under vacuum and filled with argon. The mixture was allowed to warm to r.t. and the Schlenk tube was linked to an hydrogenation apparatus. The system was flushed ten times with hydrogen and stirred 12 h at r.t. under an atmospheric pressure of hydrogen. The solvent was then removed under vacuum and the resulting slurry dissolved in Et₂O and filtered on a short silica pad. Chromatography on preparative TLC (elution with heptane-EtOAc, 85:15) of the residue afforded 1 (90 mg, 92%) as a colorless oil. ¹H NMR (300 MHz, CDCl₃): δ = 7.27 (dd, J = 8.0, 1.1 Hz, 1 H, H8), 7.17 (t, J = 8.0 Hz, 1 H, H7), 6.71 (dd, J = 7.9, 1.0 Hz, 1 H, H6), 5.59 (dqd, J = 2.7, 1.7, 0.6 Hz, 1 H, H3), 3.83 (s, 3 H, H11), 3.51 (s, 3 H, H18), 3.26 (s, 3 H, H18), 3.30-3.20 (m, 4 H, H4α, H13, H16), 3.08 (dq, J = 22.4, 2.6 Hz, 1 H, H4β), 1.88 (dd, J = 2.6, 1.7 Hz, 3 H, H19), 1.65-1.60 (m, 2 H, H14), 1.55 (s, 3 H, H12), 1.45-1.38 (m, 1 H, H15), 1.00-0.90 (m, 1 H, H15) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 155.9 (C5), 141.3 (C9), 136.2 (C2), 125.9 (C7), 124.0 (C10), 122.6 (C3), 120.5 (C8), 106.9 (C6), 88.4 (C13), 73.1 (C16), 61.8 (C18), 58.5 (C17), 55.2 (C11), 47.1 (C1), 28.9 (C15), 27.2 (C14), 25.1 (C4), 23.3 (C12), 20.5 (C19). IR (CHCl₃): ν = 1582, 1462, 1423. HRMS (ESI): m/z calcd for C₁₉H₂₈O₃: 304.2038; found: 327.1950 [M + Na].

11 For isomerization of allylamides see: Neugnot B. Cintrat JC. Rousseau B. Tetrahedron  2004,  60:  3575 

For the isomerization of allyl ethers see:

12a Nelson SG. Bungard CJ. Wang K. J. Am. Chem. Soc.  2003,  125:  13000 

12b Ohmura T. Yamamoto YY. Miyaura N. Organometallics  1999,  18:  413 ; and references therein