Page 755 - Advanced Organic Chemistry Part B - Reactions & Synthesis

8.2.3.3. Coupling with Stannanes. Another important group of cross-coupling 731
reactions, known as Stille reactions, uses aryl and alkenyl stannanes as the
organometallic component. 183 The reactions are carried out with Pd(0) catalysts in SECTION 8.2
the presence of phosphine ligands and have proven to be very general with respect Reactions Involving
Organopalladium
to the halides that can be used. Benzylic, aryl, alkenyl, and allylic halides can all be Intermediates
utilized, 184 and the groups that can be transferred from tin include alkyl, alkenyl, aryl,
and alkynyl. The approximate order of the effectiveness of transfer of groups from tin
is alkynyl > alkenyl > aryl > methyl > alkyl, so unsaturated groups are normally
transferred selectively. 185 Subsequent studies have found better ligands, including tris-
(2-furyl)phosphine 186 and triphenylarsine. 187 Aryl-aryl coupling rates are increased by
the presence of a Cu(I) cocatalyst, 188 which has led to a simplified protocol in which
Pd-C catalyst, along with CuI and Ph As, gives excellent yields of biaryls.
3
Pd/C, 0.5 mol % Pd
Cul, 10 mol %
+ (n - C H ) Sn S
4 9 3
S I Ph 3 As, 20 mol %
NMP, 80°C, 16 h 77%
Ref. 189

The general catalytic cycle of the Stille reaction involves oxidative addition,
transmetallation, and reductive elimination.

Ar′SnR 3
II
ArPd (L) X
n
transmetallation
ArX
Ar′
II
oxidative [ArPd (L) ] + R 3 SnX
n
addition
0
Pd L n
reductive elimination
Ar – Ar′
The role of the ligands is both to stabilize the Pd(0) state and to “tune” the reactivity of
the palladium. The outline mechanism above does not specify many detailed aspects
of the reaction that are important to understanding the effect of ligands, added salts,
and solvents. Moreover, it does not address the stereochemistry, either in terms of the
Pd center (tetracoordinate? pentacoordinate?, cis?, trans?) or of the reacting carbon
groups (inversion?, retention?). Some of these issues are addressed by a more detailed
mechanism. 190

183 J. K. Stille, Angew. Chem. Int. Ed. Engl., 25, 508 (1986); T. N. Mitchell, Synthesis, 803 (1992);
V. Farina, V. Krishnamurthy, and W. J. Scott, Org. React., 50, 1 (1998).
184 F. K. Sheffy, J. P. Godschalx, and J. K. Stille, J. Am. Chem. Soc., 106, 4833 (1984); I. P. Beltskaya,
J. Organomet. Chem., 250, 551 (1983); J. K. Stille and B. L. Groth, J. Am. Chem. Soc., 109, 813 (1987).
185
J. W. Labadie and J. K. Stille, J. Am. Chem. Soc., 105, 6129 (1983).
186 V. Farina and B. Krishnan, J. Am. Chem. Soc., 113, 9585 (1991).
187
V. Farina, B. Krishnan, D. R. Marshall, and G. P. Roth, J. Org. Chem., 58, 5434 (1993).
188
V. Farina, S. Kapadia, B. Krishnan, C. Wang, and L. S. Liebskind, J. Org. Chem., 59, 5905 (1994).
189 G. P. Roth, V. Farina, L. S. Liebeskind, and E. Pena-Cabrera, Tetrahedron Lett., 36, 2191 (1995).
190
P. Espinet and A. Echavarren, Angew. Chem. Int. Ed. Engl., 43, 4704 (2004).