Page 742 - Advanced Organic Chemistry Part B - Reactions & Synthesis

718 Several modified reaction conditions have been developed. One involves addition
of silver salts, which activate the halide toward displacement. 134 Use of sodium
CHAPTER 8
bicarbonate or sodium carbonate in the presence of a phase transfer catalyst permits
Reactions Involving especially mild conditions to be used for many systems. 135 Tetraalkylammonium salts
Transition Metals
also often accelerate reaction. 136 Solid phase catalysts in which the palladium is
complexed by polymer-bound phosphine groups have also been developed. 137
Aryl chlorides are not very reactive under normal Heck reaction conditions but
reaction can be achieved by inclusion of tetraphenylphosphonium salts with Pd OAc 2
or PdCl as the catalysts. 138
2

Pd(CH CN) Cl , 2 mol %
2
2
3
Cl + CH CH 2 + –
NaO 2 CCH , Ph P Cl
3
4
NMP 79%
Pretreatment with nickel bromide causes normally unreactive aryl chlorides to undergo
Pd-catalyzed substitution, 139 and aryl and vinyl triflates have been found to be excellent
substrates for Pd-catalyzed alkenylations. 140
Heck reactions can be carried out in the absence of phosphine ligands. 141 These
conditions usually involve Pd OAc as a catalyst, along with a base and a phase
2
transfer salt such as tetra-n-butylammonium bromide. These conditions were originally
applied to stereospecific coupling of vinyl iodides with ethyl acrylate and methyl vinyl
ketone.

0.02 mol % Pd(OAc) 2
4 9
4
C H I + CH 2 CHCO CH 3 1 equiv Bu NCl C H CO CH
2
4 9
2.5 equiv K CO 3 2 3
2
DMF, 25°C 90%
Several optimization studies have been carried out under these phosphine-free
conditions. The reaction of bromobenzene and styrene was studied using Pd OAc
2
as the catalyst, and potassium phosphate and N,N-dimethylacetamide (DMA) were
found to be the best base and solvent. Under these conditions, the Pd content can be
reduced to as low as 0.025 mol %. 142 The reaction of substituted bromobenzenes with
methyl -acetamidoacrylate has also been studied carefully, since the products are
potential precursors of modified amino acids. Good results were obtained using either
N N-diisopropylethylamine or NaOAc as the base.

134
M. M. Abelman, T. Oh, and L. E. Overman, J. Org. Chem., 52, 4130 (1987); M. M. Abelman and
L. E. Overman, J. Am. Chem. Soc., 110, 2328 (1988).
135
T. Jeffery, J. Chem. Soc., Chem. Commun., 1287 (1984); T. Jeffery, Tetrahedron Lett., 26, 2667 (1985);
T. Jeffery, Synthesis, 70 (1987); R. C. Larock and S. Babu, Tetrahedron Lett., 28, 5291 (1987).
136 A. de Meijere and F. E. Meyer, Angew. Chem. Int. Ed. Engl., 33, 2379 (1994); R. Grigg, J. Heterocycl.
Chem., 31, 631 (1994); T. Jeffery, Tetrahedron, 52, 10113 (1996).
137
C.-M. Andersson, K. Karabelas, A. Hallberg, and C. Andersson, J. Org. Chem., 50, 3891 (1985).
138 M. T. Reetz, G. Lehmer, and R. Schwickard, Angew. Chem. Int. Ed., 37, 481 (1998).
139 J. J. Bozell and C. E. Vogt, J. Am. Chem. Soc., 110, 2655 (1988).
140
A. M. Echavarren and J. K. Stille, J. Am. Chem. Soc., 109, 5478 (1987); K. Karabelas and A. Hallberg,
J. Org. Chem., 53, 4909 (1988).
141 T. Jeffery, Tetrahedron Lett., 26, 2667 (1985); T. Jeffery, Synthesis, 70 (1980).
142
Q. Yao, E. P. Kinney, and Z. Yang, J. Org. Chem., 68, 7528 (2003).