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
References and Notes
1a </A>
Hoshino O. In
The Alkaloids
Vol. 51:
Cordell GA.
Academic Press;
San Diego:
1998.
p.323
1b </A>
Lewis JR.
Nat. Prod. Rep.
2000,
17:
57
1c </A>
Lewis JR.
Nat. Prod. Rep.
1998,
15:
107
2a </A>
Ríos JL.
Máñez S.
Giner RM.
Recio MC. In The Alkaloids
Vol. 53:
Cordell GA.
Academic Press;
New York:
2000.
p.57
2b </A>
Guinaudeau H.
Leboeaf M.
Cavé A.
J. Nat. Prod.
1994,
57:
1033 ; and references cited therein
3a </A>
Alberico D.
Scott ME.
Lautens M.
Chem. Rev.
2007,
107:
174
3b </A>
Campeau
L.-C.
Fagnou K.
Chem. Commun.
2006,
1253
3c </A>
Echavarren AM.
Gómez-Lor B.
González JJ.
de Frutos Ó.
Synlett
2003,
585
4a </A>
Harayama T.
Hori A.
Abe H.
Takeuchi Y.
Tetrahedron
2004,
60:
1611
4b </A>
Torres JC.
Pinto AC.
Garden SJ.
Tetrahedron
2004,
60:
9889
<A NAME="RW13407ST-5">5 </A>
Echavarren AM.
Gómez-Lor B.
Org. Lett.
2004,
6:
2993
6a </A>
Cuny GD.
Tetrahedron Lett.
2003,
44:
8149
6b </A>
Cuny GD.
Tetrahedron Lett.
2004,
45:
5167
7a </A>
Lafrance M.
Blaquière N.
Fagnou K.
Chem. Commun.
2004,
2874
7b </A> For synthesis of 9-arylphenanthrenes, see:
García-Cuadrado D.
de Mendoza P.
Braga AAC.
Maseras F.
Echavarren AM.
J. Am. Chem. Soc.
2007,
129:
6880
8a </A>
Cuny G.
Bois-Choussy M.
Zhu J.
Angew. Chem. Int. Ed.
2003,
42:
4774
8b </A>
Cuny G.
Bois-Choussy M.
Zhu J.
J. Am. Chem. Soc.
2004,
126:
14475
9a </A>
Tan KL.
Vasudevan A.
Bergman RG.
Ellman JA.
Souers AJ.
Org. Lett.
2003,
5:
2131
9b </A>
Lewis JC.
Wu JY.
Bergman RG.
Ellman JA.
Angew. Chem. Int. Ed.
2006,
45:
1589
9c </A> Using palladium catalyst, see:
Sridharan V.
Martín MA.
Menendez JC.
Synlett
2006,
2375
9d </A> Using nickel catalyst, see:
Cioffi EA.
Bell RH.
Le B.
Tetrahedron: Asymmetry
2005,
16:
471
9e </A>
Larhed M.
Moberg C.
Hallberg A.
Acc. Chem. Res.
2002,
35:
717
9f </A>
Roberts BA.
Strauss CR.
Acc. Chem. Res.
2005,
38:
653
10a </A>
Nüchter M.
Ondruschka B.
Bonrath W.
Gum A.
Green Chem.
2004,
43:
128
10b </A>
Kappe CO.
Angew. Chem. Int. Ed.
2004,
43:
6250
10c </A>
Kappe CO.
Stadler A.
Microwaves in Organic and Medicinal Chemistry
Wiley-VCH;
Weinheim:
2005.
10d </A>
Microwaves in Organic Synthesis
Vol. 1 and 2:
Loupy A.
Wiley-VCH;
Weinheim:
2006.
11a </A>
Dai W.-M.
Guo D.-S.
Sun L.-P.
Tetrahedron Lett.
2001,
42:
5275
11b </A>
Dai W.-M.
Sun L.-P.
Guo D.-S.
Tetrahedron Lett.
2002,
43:
7699
11c </A>
Dai W.-M.
Guo D.-S.
Sun L.-P.
Huang X.-H.
Org. Lett.
2003,
5:
2919
11d </A>
Sun L.-P.
Huang X.-H.
Dai W.-M.
Tetrahedron
2004,
60:
10983
11e </A>
Sun L.-P.
Dai W.-M.
Angew. Chem. Int. Ed.
2006,
45:
7255
<A NAME="RW13407ST-12">12 </A> For synthesis of benzo[b ]furanes, see:
Dai W.-M.
Lai KW.
Tetrahedron Lett.
2002,
43:
9677
13a </A>
Dai W.-M.
Wang X.
Ma C.
Tetrahedron
2005,
61:
6879
13b </A>
Feng G.
Wu J.
Dai W.-M.
Tetrahedron
2006,
62:
4635
13c </A>
Xing X.
Wu J.
Feng G.
Dai W.-M.
Tetrahedron
2006,
62:
6774
13d </A>
Feng G.
Wu J.
Dai W.-M.
Tetrahedron Lett.
2007,
48:
401
<A NAME="RW13407ST-14">14 </A> For synthesis of tetrahydroquinolines, see:
Xing X.
Wu J.
Dai W.-M.
Tetrahedron
2006,
62:
11200
<A NAME="RW13407ST-15">15 </A> For synthesis of the conjugates of dibenz[b ,f ][1,4]oxazepine with 2-oxindole, see:
Xing X.
Wu J.
Luo J.
Dai W.-M.
Synlett
2006,
2099
<A NAME="RW13407ST-16">16 </A>
Abdel-Magid AF.
Carson KG.
Harris BD.
Maryanoff CA.
Shah RD.
J. Org. Chem.
1996,
61:
3849
<A NAME="RW13407ST-17">17 </A>
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 K2 CO3 (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. H2 O (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 Na2 SO4 , and evaporated under reduced pressure. The residue was purified by column chromatography
on silica gel to furnish the product (see Table
[3 4 7e : IR (KBr): 1672, 1236 cm-1 . 1 H 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). 13 C 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 C16 H12 ClNO2 : C, 67.26; H, 4.23; N, 4.90. Found: C, 67.28; H, 4.22; N, 4.88. The 1 H NMR and 13 C NMR of 7a -f and 16 can be obtained from the authors upon request.
18a </A>
Dai W.-M.
Li Y.
Zhang Y.
Lai KW.
Wu J.
Tetrahedron Lett.
2004,
45:
1999
18b </A>
Dai W.-M.
Zhang Y.
Tetrahedron Lett.
2005,
46:
1377
18c </A>
Jin J.
Chen Y.
Li Y.
Wu J.
Dai W.-M.
Org. Lett.
2007,
9:
2585
