Page 773 - Advanced Organic Chemistry Part B - Reactions & Synthesis

RCH CH 2 749
II
Pd II Pd , CO
–
"H " R′OH O SECTION 8.2
Pd II Reactions Involving
+ II O C Pd II + RCHCH 2 C Pd II Organopalladium
RCH CH 3 RCH CH 2 Pd Intermediates
2
RCHCH OR′ OR′
CO 2
O
O C Pd II
+ RCH 2 CH 2 C Pd II R′OH
RCH CH 3
R′OH RCHCH OR′ + RCHCH CO R′
2
2
2
CO R′ OR′
CO R′ 2
2
+ RCH CH CO R′
2
2
2
RCHCH 3 solvocarbonylation
hydrocarbonylation
8.2.4.1. Hydrocarbonylation. The hydrocarbonylation reaction can be applied to
the synthesis of -arylpropanoic acids of the NSAIDS type. 239 For this synthesis
to be effective, selective carbonylation of the more-substituted sp 2 carbon is
required. Although many carbonylation conditions are unselective, PdCl PPh with
3 2
2
p-toluenesulfonic acid and LiCl achieves excellent selectivity, which is thought to
involve the formation of a benzylic chloride intermediate.
C H SO H
3
7 7
ArCH CH 2 ArCHCH 3 Pd(0) ArCHCH 3
LiCl
CO, H O
Cl 2 CO H
2
Naproxen can be synthesized in 89% yield with 97.5% regioselectivity under these
conditions.
2 mol % PdCl (PPh ) CH 3
3 2
2
CH 2 20 mol % LiCl
20 mol % TsOH CO 2 H
CH O 12 equiv H O
3
2
2-butanone, 115°C CH O 89%
3

This reaction has been done with good enantioselectivity using 1 1 -binaphthyl-2 2 -
diyl hydrogen phosphate (BNPPA) as a chiral ligand. 240
CH 3
15 mol % PdCl 2 CO 2 H
5 mol % S -BNPPA
CH O 1 atm CO, O2 CH O
3
3
HCl, H O, THF
2
89% yield, 83% e.e.
When conducting hydrocarbonylations with dienes, it was found that a mixture of
nonchelating and bidentate phosphine ligands was beneficial. 241
239
A Seayad, S. Jayasree, and R. V. Chaudhari, Org. Lett., 1, 459 (1999).
240 H. Alper and N. Hamel, J. Am. Chem. Soc., 112, 2803 (1990).
241
G. Vasapollo, A. Somasunderam, B. El Ali, and H. Alper, Tetrahedron Lett., 35, 6203 (1994).