Page 477 - Advanced Organic Chemistry Part B - Reactions & Synthesis

450 Another important reductive coupling is the conversion of esters to
-hydroxyketones (acyloin condensation). 267 This reaction is usually carried out with
CHAPTER 5 sodium metal in an inert solvent. Good results have also been obtained for sodium
Reduction of metal dispersed on solid supports. 268 Diesters undergo intramolecular reactions and
Carbon-Carbon Multiple
Bonds, Carbonyl this is also an important method for the preparation of medium and large carbocyclic
Groups, and Other rings.
Functional Groups
1) Na O
CH O C(CH ) CO CH 3
2 8
3
2
2
CO H
2) CH 3 2 OH
Ref. 269
There has been considerable discussion of the mechanism of the acyloin conden-
sation. One formulation of the reaction envisages coupling of radicals generated by
one-electron transfer.

O O – – O O – O O – O O – + O
RCOR′ + Na RCOR′ RC CR RC CR 2Na H RCCHR
• RC CR
R′OOR′ OH

An alternative mechanism bypasses the postulated -diketone intermediate because its
involvement is doubtful. 270

O – OR′ OR′ OR′ OR′ OR′
RCO R′
2
RCO R′ + Na RCOR′ RC C OR Na RC O CR RC CR
2
.
. –
O – O – O O –
Na
OR′ OR′ – O O –
. Na –
RC CR RC CR RC CR
– – – –
O O O O
Regardless of the details of the mechanism, the product prior to neutralization
is the dianion of an -hydroxy ketone, namely an enediolate. It has been found that
the overall yields are greatly improved if trimethylsilyl chloride is present during the
reduction to trap these dianions as trimethylsilyl ethers. 271 The silylated derivatives
are much more stable to the reaction conditions than the enediolates. Hydrolysis
during workup gives the acyloin product. This modified version of the reaction has
been applied to cyclizations leading to small, medium, and large rings, as well as to
intermolecular couplings.
Scheme 5.13 provides several examples of reductive carbon-carbon bond
formation, including formation of diols, alkenes, and acyloins. Entry 1 uses magnesium
amalgam in the presence of dichlorodimethylsilane. The role of the silane may be to

267 J. J. Bloomfield, D. C. Owsley, and J. M. Nelke, Org. React., 23, 259 (1976).
268
M. Makosza and K. Grela, Synlett, 267 (1997); M. Makosza, P. Nieczypor, and K. Grela, Tetrahedron,
54, 10827 (1998).
269
N. Allinger, Org. Synth., IV, 840 (1963).
270 J. J. Bloomfield, D. C. Owsley, C. Ainsworth, and R. E. Robertson, J. Org. Chem., 40, 393 (1975).
271
K. Ruhlmann, Synthesis, 236 (1971).