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.

Key words

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 
• 2 Yadav JS. Reddy BVS. Gupta MK. Prabhakar A. Jagadeesh B. Chem. Commun.  2004,  2124 
• 3 Rudler H. Denise B. Parlier A. Daran J.-C. Eur. J. Org. Chem.  2005,  3724 
• 4 Ullah E. Rotzoll S. Schmidt A. Michalik D. Langer P. Tetrahedron Lett.  2005,  46:  8997 
• 5 Albrecht U. Armbrust H. Langer P. Synlett  2004,  143 
• 6 Review: Langer P. Synthesis  2002,  441 
• 7a Schmidt A. Gütlein J.-P. Preuss A. Albrecht U. Reinke H. Langer P. Synlett  2005,  2489 
• 7b Schmidt A. Gütlein J.-P. Langer P. Tetrahedron Lett.  2007,  48:  2067 
• 8a Chan T.-H. Brownbridge P. J. Am. Chem. Soc.  1980,  102:  3534 
• 8b Molander GA. Cameron KO. J. Am. Chem. Soc.  1993,  115:  830 
• 8c Krägeloh K. Simchen G. Synthesis  1981,  30 
• 10 Chilin A. Marzaro G. Zanatta S. Barbieri V. Pastorini G. Manzini P. Guiotto A. Tetrahedron  2006,  62:  12351 

9

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.

11

CCDC-617334 contains all crystallographic details of this publication and is available free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html or can be ordered from the following address: Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB21EZ, UK; fax: [phone]; or [e-mail].