Preparation of Highly Functionalized Heterocyclic Zinc Organometallics via a Li(acac)-Catalysis of the I/Zn-Exchange Reaction

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

• 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 

1

Visiting professor from Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences.

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.