Ruthenium-Mediated Isomerization and Ring-Closing Metathesis: Versatile Syntheses of 6-, 7- and 8-Membered Benzo-Fused Heterocycles

Abstract

Ruthenium-mediated isomerization and ring-closing metathesis (RCM) were the key steps used to convert a simple substrate, 2-allyl-3-isopropoxy-4-methoxybenzaldehyde, into a variety of 6-, 7- and 8-membered nitrogen- and oxygen-containing benzo-fused heterocycles.

ruthenium catalysts - metathesis - ring closure - isomerizations

References

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23

Taken from the ongoing PhD of Rakhi Pathak.

24

To a degassed solution of N-allyl-N-(2-allyl-3-isopropoxy-4-methoxybenzyl)-4-methylbenzenesulfonamide (4b) (120 mg) in toluene (10 cm³) was added [RuClH(CO)(PPh₃)₃] (0.5 mol%). The reaction mixture was heated at 110 °C for 2 h under a N₂ atmosphere. Grubbs’ catalyst 1 (5 mol%) was added and the reaction mixture was stirred for another 3 h at 110 °C under N₂. After cooling the mixture, the toluene was evaporated under reduced pressure and the organic residue was then subjected to silica gel column chromatography (5-20% EtOAc-hexane) to afford the desired product, 5-isopropoxy-2-[(4-methylphenyl)sulfonyl]-1,2-dihydro-6-isoquinolinylmethyl ether (7) as a brown oil (0.079 g, 76%). Found: M⁺, 373.1348. C₂₀H₂₃NSO₄ requires M⁺, 373.1348. IR (CHCl₃): ν_max = 1625 and 1597 (ArC=C) and 1167 (NSO₂) cm^-1. ¹H NMR (300 MHz, CDCl₃, Me₄Si): δ = 1.21 [6 H, d, J = 6.2 Hz, CH(CH ₃)₂], 2.37 (3 H, s, ArCH₃), 3.77 (3 H, s, OCH₃), 4.35 {1 H, sept, J = 6.2 Hz, [CH(CH₃)₂]}, 4.48 (2 H, s, NCH₂), 6.22 (1 H, d, J = 7.9 Hz, ArCH=CH), 6.64 (2 H, s, 7-ArH and 8-ArH), 6.74 (1 H, d, J = 7.9 Hz, NCH=CHAr), 7.25 (2 H, d, J = 8.1 Hz, 2 × ArH), 7.67 (2 H, d, J = 8.1 Hz, 2 × ArH). ¹³C NMR (75 MHz, CDCl₃): δ = 21.4 (ArCH₃), 22.4 [CH(CH₃)₂], 46.8 (NCH₂), 55.7 (OCH₃), 75.2 [CH(CH₃)₂], 106.3 (CH), 110.7 (CH), 120.4 (CH), 120.7 (C), 125.3 (C), 126.1 (CH), 126.9 (C), 127.1 (2 × CH), 129.2 (C), 129.7 (2 × CH), 143.9 (C), 152.4 (C). MS:
m/z (%) = 374 (24), 373 (90) [M⁺], 218 (18), 176 (100),
175 (89), 161 (35), 144 (45), 132 (30) and 91 (43).

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