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Synlett 2007(17): 2728-2732  
DOI: 10.1055/s-2007-991053
LETTER
© Georg Thieme Verlag Stuttgart · New York

Microwave-Assisted, Palladium-Catalyzed Intramolecular Direct Arylation for the Synthesis of Novel Fused Heterocycles

Jinlong Wua, Liang Niea, Jialu Luoa, Wei-Min Dai*a,b
a Laboratory of Asymmetric Catalysis and Synthesis, Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. of China
Fax: +86(571)87953128; e-Mail: chdai@zju.edu.cn;
b Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, P. R. of China
Fax: +85223581594; e-Mail: chdai@ust.hk;
Further Information

Publication History

Received 20 July 2007
Publication Date:
25 September 2007 (online)

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Abstract

An efficient synthesis of novel fused heterocycles has been established via microwave-assisted palladium-catalyzed intramolecular direct arylation. The acyclic aryl bromides are readily available from microwave-assisted one-pot annulation of N-(2-bromobenzyl)-2-aminophenols and ethyl 2-bromoalkanoates. The intramolecular direct arylation is then performed in the presence of palladium(II) acetate and dppf (10 mol% each) in toluene using potassium carbonate (2 equiv) as the base under microwave heating (150 °C, 1 h) to afford the products in 43-99% yields. Steric effect is observed for Ar-Ar bond formation, giving a substantial amount of the debromination byproduct.

Key words

3,4-dihydro-3-oxo-2H-1,4-benzoxazine - direct arylation - heterocycles - microwave - palladium

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General Procedure for Pd-Catalyzed Direct Arylation: A 10 mL pressurized process vial was charged with the bromide 8 (0.50 mmol), Pd(OAc)2 (0.05 mmol), dppf (0.05 mmol), and K2CO3 (1.00 mmol) and it was sealed with a cap containing a silicon septum. The vial was then evacuated and backfilled with N2 (repeated for several times) through the cap using a needle. To the degassed vial was added degassed anhyd toluene (3 mL) through the cap using a syringe. The loaded vial was then placed into the microwave reactor cavity and was heated at 150 °C for 1 h. After cooled to r.t. H2O (5 mL) was added to the reaction vial. The resultant mixture was then extracted with EtOAc (3 × 10 mL). The combined organic layer was washed with brine, dried over anhyd Na2SO4, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel to furnish the product (see Table [3] and Scheme [4] for details). Spectroscopic data for 7e: IR (KBr): 1672, 1236 cm-1. 1H NMR (400 MHz, CDCl3): d = 8.49 (d, J = 7.6 Hz, 1 H), 7.43-7.32 (m, 3 H), 7.16 (d, J = 8.4 Hz, 1 H), 6.89 (d, J = 8.8 Hz, 1 H), 5.13 and 4.61 (ABq, J = 14.8 Hz, 2 H), 4.54 (q, J = 6.8 Hz, 1 H), 1.57 (d, J = 6.8 Hz, 3 H). 13C NMR (100 MHz, CDCl3): d = 164.6, 143.9, 132.2, 129.0, 128.5, 127.6, 127.5, 127.2, 126.8, 126.6, 124.4, 122.8, 116.2, 73.4, 42.6, 15.5. MS (ESI+): m/z (%) = 308 (100) [M + Na+]. Anal. Calcd for C16H12ClNO2: C, 67.26; H, 4.23; N, 4.90. Found: C, 67.28; H, 4.22; N, 4.88. The 1H NMR and 13C NMR of 7a-f and 16 can be obtained from the authors upon request.