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OCF
3
F
3
CO
I
CO
2
R
O
CO
2
R
50
Pd
2
(dba)
3
PPh
3
,Ag
2
O
DME, 60
o
C
O
N
H
BPin
H
Ph
Ph
49
51,
e.r. = > 95.5 (R=
t
Bu)
48,
e.r. = 94:6 (R=H)
(11
:
15)
Remarkably, the Ag
2
O-mediated protocol, so effective at coupling
benzylic boronic esters, was found to be completely ineffective with purely
aliphatic primary or secondary nucleophiles in the absence of other
bases [eqn (11.16)]. Thus the linear hydroboration product (52) is unreactive
whereas the branched isomer reacts in good yield.
42
Ar-I
Pd
2
(dba)
3
PPh
3
,Ag
2
O
DME 80°C
BPin
No reaction
Ph
(11
:
16)
52
As a clue to the origin of this effect, although simple n-alkyl- or even
sec-alkylboronic esters do not couple under the silver(I) oxide conditions,
installing a single site of p-unsaturation proximal to the secondary boronic
ester renders the resulting allylic boronic esters reactive under optimized
conditions (Scheme 11.4).
54
This discovery led to the first general protocol
for the cross-coupling of secondary allylic boronic esters. The position of
arylation is dictated by the nature of the substituents on the allylic boronic
ester, with coupling taking place typically at the g-position, except in the case
of styrenyl systems such as 58, in which a-selective coupling is observed
(Scheme 11.5).
In a collaboration between the Aggarwal and Crudden groups,
55
this re-
action was expanded to include enantiomerically enriched boronic esters
and mechanistic details elucidated by the use of deuterated substrates.
Interestingly, unlike the case of benzylic boronic esters (17), optimal reaction
BPin
no reaction
53
ArI
Pd
2
(dba)
3
, PPh
3
Ag
2
O
DME, 80°C
BPin
Ar
54
55
60% yield
Scheme 11.4 Effect of allylic unsaturation on Suzuki-Miyaura cross-coupling of
secondary boronic esters.
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