Synthesis of 7,8-Benzo-4-hydroxy-1,9-diazabicyclo[3.3.1]non-3-enes by Cyclization of 1,3-Bis(silyl enol ethers) with Quinazoline

Abstract

Functionalized 7,8-benzo-4-hydroxy-1,9-diazabicyclo[3.3.1]non-3-enes were prepared by one-pot cyclization of 1,3-bis(silyl enol ethers) with quinazolines.

cyclizations - N-heterocycles - iminium salts - quinazolines - silyl enol ethers

References and Notes

1 Scriven EFV. Pyridines and their Benzo Derivatives:(ii) Reactivity at Ring Atoms, In Comprehensive Heterocyclic Chemistry   Vol. 2, Part 2A:  Boulton AJ. McKillop A. Katritzky AR. Rees CW. Elsevier Science; Oxford: 1984.  Chapt. 2.05. p.165 

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5 Albrecht U. Armbrust H. Langer P. Synlett  2004,  143 

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7a Schmidt A. Gütlein J.-P. Preuss A. Albrecht U. Reinke H. Langer P. Synlett  2005,  2489 

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General Procedure for the Cyclization of Quinazolines with 1,3-Bis(silyl enol ethers) To a CH₂Cl₂ soln (40 mL) of quinazoline (0.521 g, 4.0 mmol) was added the 1,3-bis(silyl enol ether) (5.6 mmol) and methyl chloroformate (1.512 g, 16.0 mmol) at 0 °C. The solution was stirred for 2 h at 0 °C and for 12 h at 20 °C. The solvent was removed in vacuo. The residue was purified by chromatography (silica gel, heptane → heptane-EtOAc = 2:1).
Synthesis of 3a
Starting from quinazoline (0.521 g, 4.0 mmol), 2a (1.460 g, 5.6 mmol) and methyl chloroformate (1.512 g, 16.0 mmol), 3a was obtained as a colorless solid (0.750 g, 52%). ¹H NMR (250 MHz, CDCl₃): δ = 2.41 (dd, ² J = 17.5 Hz, ³ J = 1.5 Hz, 1 H, CH₂), 2.99 (br dd, 1 H, CH₂), 3.76 (s, 3 H, OCH₃), 3.80 (s, 3 H, OCH₃), 3.87 (s, 3 H, OCH₃), 5.40 (br, 1 H, NCHCH₂), 7.03-7.13 (m, 2 H, CH, Ar), 7.20-7.26 (m, 1 H, CH, Ar), 7.38 (br, 1 H, NCH), 7.75 (br, 1 H, CH, Ar), 12.26 (s, 1 H, OH). ¹³C NMR (75.5 MHz, CDCl₃): δ = 38.0 (CH₂), 48.7 (br, NCHCH₂), 52.0, 53.2, 53.3 (OCH₃), 58.9 (NCH), 98.0 (CCO₂CH₃), 124.2, 124.4, 126.8, 127.6 (CH, Ar), 126.3, 134.4 (br, C, Ar), 153.4, 154.0 (NCO), 170.6 (COO), 173.2 (br, COH). IR (mull): 3080 (w), 1707 (s), 1652 (m), 1613 (m), 1494 (m), 1335 (m), 1287 (s), 1263 (m), 1230 (s), 1196 (m), 1142 (m), 1111 (m), 1064 (m), 1039 (m), 1008 (m), 954 (w), 873 (w), 824 (w), 778 (m), 737 (w) cm^-1. MS (EI, 70 eV): m/z (%) = 362 (10) [M⁺], 303 (100), 271 (36), 212 (23), 180 (21), 239 (13). Anal. Calcd for C₁₇H₁₈N₂O₇ (362.33): C, 56.35; H, 5.01; N, 7.73. Found: C, 56.35; H, 5.13; N, 7.46.

10 Chilin A. Marzaro G. Zanatta S. Barbieri V. Pastorini G. Manzini P. Guiotto A. Tetrahedron  2006,  62:  12351 

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