Abstract
The reaction of i-Pr2Zn in the presence of catalytic amount of Li(acac) in NMP with various functionalized heterocyclic iodides provides new polyfunctional diheteroarylzincs, which undergo smooth Negishi cross-coupling reactions and CuCN·2LiCl-catalyzed allylation reactions under mild conditions. Remarkably, even an aldehyde function can be present in the diorganozinc reagents.
Key words
polyfunctional heterocycles - iodine-zinc exchange reaction - diorganozinc reagent - catalysis - cross-coupling
References
1 Visiting professor from Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences.
2a
Gilchrist TL.
Heterocyclic Chemistry
Longman;
Harlow, UK:
1997.
2b
Joule JA.
Mills K.
Smith GF.
Heterocyclic Chemistry
Stanley Thornes;
Cheltenham, UK:
1998.
3a
Cai X.
Snieckus V.
Org. Lett.
2004,
6:
2293
3b
Hartung CG.
Fecher A.
Chapell B.
Snieckus V.
Org. Lett.
2003,
5:
1899
3c
Chauder B.
Larkin A.
Snieckus V.
Org. Lett.
2002,
4:
815
3d
Chauder B.
Green L.
Snieckus V.
Pure Appl. Chem.
1999,
71:
1521
3e
Audoux J.
Plé N.
Turck A.
Quéguiner G.
Tetrahedron
2004,
60:
6353
3f
Rebstock A.-S.
Mongin F.
Trécourt F.
Quéguiner G.
Tetrahedron
2004,
60:
2181
3g
Dumouchel S.
Mongin F.
Trécourt F.
Quéguiner G.
Tetrahedron
2003,
59:
8629
3h
Quéguiner G.
J. Heterocycl. Chem.
2000,
37:
615
4 For the preparation of some Grignard reagents with a keto group, see: Kneisel FF.
Knochel P.
Synlett
2002,
1799
5
Kneisel FF.
Dochnahl M.
Knochel P.
Angew. Chem. Int. Ed.
2004,
43:
1017
6a
Farina V.
Krishnan B.
J. Am. Chem. Soc.
1991,
113:
9585
6b
Farina V.
Kapadia S.
Krishnan B.
Wang C.
Liebeskind LS.
J. Org. Chem.
1994,
59:
5905
7a
Negishi E.
Valente LF.
Kobayashi M.
J. Am. Chem. Soc.
1980,
102:
3298
7b
Kobayashi M.
Negishi E.
J. Org. Chem.
1980,
45:
5223
7c
Negishi E.
Acc. Chem. Res.
1982,
15:
340
7d
Tamaru Y.
Ochiai H.
Nakamura T.
Yoshida Z.
Tetrahedron Lett.
1986,
27:
955
8
Knochel P.
Yeh MCP.
Berk SC.
Talbert J.
J. Org. Chem.
1988,
53:
2390
9
Villieras J.
Rambaud M.
Synthesis
1982,
924
10
Sakamoto T.
Kondo Y.
Takazawa N.
Yamanaka H.
J. Chem. Soc., Perkin Trans. 1
1996,
1927
11a
Liu Y.
Gribble GW.
Tetrahedron Lett.
2000,
41:
8717
11b
Bergman J.
Venemalm L.
J. Org. Chem.
1992,
57:
2495
11c
Saulnier MG.
Gribble GW.
J. Org. Chem.
1982,
47:
757
12
Yang X.
Althammer A.
Knochel P.
Org. Lett.
2004,
6:
1665
13
Collot V.
Varlet D.
Rault S.
Tetrahedron Lett.
2000,
41:
4363
14
Gordon DW.
Synlett
1998,
1065
15
Typical Procedure for the Preparation of 4-Pyridin-3-yl-benzoic Acid Methyl Ester (
7a):
To a solution of 3-iodopyridine 5a (205 mg, 1.0 mmol) and Li(acac) (11 mg, 0.1 mmol) in anhydrous and degassed NMP (1 mL) was added i-Pr2Zn (5.0 M, 0.11 mL, 0.55 mmol) dropwise at r.t. under argon. The reaction mixture was stirred at r.t. for 12 h. The complete conversion of 3-iodopyridine to the zinc reagent was monitored by GC analysis. The zinc reagent 6a was treated with a solution of Pd(bda)2 (14 mg, 0.025 mmol), tri(2-furyl)phosphine (12 mg, 0.05 mmol) and methyl 4-iodobenzoate (393 mg, 1.5 mmol) in THF (2 mL). The resulting mixture was stirred at r.t. for 12 h, and was quenched with sat. aq NH4Cl. The aqueous layer was extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with brine and dried (Na2SO4). After removal of the solvent, the residue was purified by column chromatography on silica gel (EtOAc-pentane = 1:2) to give the desired product 7a (176 mg, 83%) as a yellow solid; mp 102.0-102.8 °C. 1HMNR (300 MHz, CDCl3): δ = 3.93 (s, 3 H), 7.31-7.42 (m, 1 H), 7.63 (d, J = 8.4 Hz, 2 H), 7.90 (td, J = 7.9, 2.2, 1.8 Hz, 1 H), 8.12 (d, J = 8.8 Hz, 2 H), 8.62 (dd, J = 1.3, 4.9 Hz, 1 H), 8.86 (dd, J = 0.9, 2.2 Hz, 1 H) ppm. 13C NMR (75 MHz): δ = 52.2, 123.7, 127.1, 129.8, 130.4, 134.7, 135.7, 142.0, 148.0, 148.9, 166.7. IR (KBr): 2951, 1721, 1608, 1285, 1107, 767 cm-1. HRMS (EI): m/z calcd for C13H11NO2: 213.0790; found: 213.0795.
