Page 697 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

The kinetics of reaction of Grignard reagents with ketones is also subject to a 679
number of complications. The purity of the magnesium metal used in the preparation of
the Grignard reagent is crucial since trace transition metal impurities have a major effect SECTION 7.6
on the observed reaction rates. One of the most thorough studies available involves the Addition of
Organometallic Reagents
reaction of methylmagnesium bromide with 2-methylbenzophenone in diethyl ether. 84 to Carbonyl Groups
The results suggest a mechanism similar to that discussed for alkyllithium reactions.
There is initial complexation between the ketone and Grignard reagent. The main
Grignard species, CH MgBr, is in equilibrium with CH Mg, which can contribute
3 3 2
to the overall rate. The product alkoxide forms a complex with the Grignard reagent to
give yet another reactive species. The general mechanistic scheme is outlined below.

2 R'MgX MgX 2 + R' 2 Mg
R' R'
M
R 2 C O + R'MgX [R 2 C O ----MgX] R C O MgX
R
R' R'
X
R C O MgX + R'MgX R C O Mg Mg R
R R X

R' R'
X X R'
R C O Mg Mg R + R 2 C O R C O Mg Mg O R
R X R X R

There is another possible mechanism for addition of organometallic reagents to
carbonyl compounds, which involves a discrete electron transfer step. 85
R'
+
–
.
R C O + (R'M) n [R C O (MR') ] [R C . O (MR') ] R O M + (R'M) n-1
+
–
2
2
n
2
n
R
The distinguishing feature of this mechanism is the second step, in which an electron
is transferred from the organometallic reagent to the carbonyl compound to give the
radical anion of the carbonyl compound. Subsequent collapse of the radical ion pair
with transfer of an alkyl group to carbon gives the same product that is formed by
the direct nucleophilic addition mechanism. The electron transfer mechanism would
be expected to be favored by structural features that stabilize the radical anion inter-
mediate. Aryl ketones and diones fulfill this requirement and evidence for the electron
transfer mechanism has been accumulated for such ketones. In several cases it is
possible to observe a radical anion intermediate by ESR spectroscopy. 86 (See Section
11.1.3 for a discussion of some of the limits of this methodology.) The relative impor-
tance of the electron transfer mechanisms also depends on the ease of oxidation of
the organometallic reagent. Allyllithium is particularly likely to react by the electron
transfer mechanism because of its ease of oxidation. 87
84
E. C. Ashby, J. Laemmle, and H. M. Neumann, J. Am. Chem. Soc., 94, 5421 (1972).
85
E. C. Ashby, Pure Appl. Chem., 52, 545 (1980); E. C. Ashby, J. Laemmle, and H. M. Neuman, Acc.
Chem. Res., 7, 272 (1974).
86 K. Maruyama and T. Katagiri, J. Am. Chem. Soc., 108, 6263 (1986); E. C. Ashby and A. B. Goel,
J. Am. Chem. Soc., 103, 4983 (1981); T. Lund, M. L. Pedersen, and L. A. Frandsen, Tetrahedron Lett.,
35, 9225 (1994).
87
J. J. Gajewski, W. Bocian, N. J. Harris, L. P. Olson, and J. P. Gajewski, J. Am. Chem. Soc., 121, 326
(1999).