Chemistry Reference
In-Depth Information
Secondary aliphatic boranes or boronic acids and esters are exceptionally
interesting substrates since they provide the opportunity to prepare enan-
tiomerically enriched products. However, these compounds have been ex-
tremely dicult compounds to engage in the Suzuki-Miyaura reaction.
Transmetallation to Pd is problematic for branched substrates, likely be-
cause of the increased steric hindrance of the secondary site. In an elegant
demonstration of this, Zou and Falck prepared the dialkyl pinacol boronate
7, in which a primary and a secondary butyl group both compete for
transmetallation to Pd.
17
In all cases, the only product observed was that
resulting from transmetallation and then coupling of the primary alkyl
substituent [eqn (11.3)]. This follows from early work of Miyaura et al., who
similarly demonstrated that in triorganoboranes containing both primary
and secondary alkyl groups, only the primary group participates in coupling
[eqn (11.4)].
13
In the absence of n-alkyl substituents, secondary alkyl groups
do react,
13
but the involvement of b-hydride elimination/addition sequences
is not possible to assess, as will be elaborated on later in this chapter [eqn
(11.5)]. Interestingly, this early work also demonstrated the relative resist-
ance of the corresponding boronic ester derivative to coupling in com-
parison with trialkylboranes.
O
ArX
B
Li
(11
:
3)
P(
t
Bu)
3
KF
Ar
Pd
O
8
exclusive product
7
PhI
Pd(dppf)Cl
2
NaOH
B
n
Oct
Ph
-
n
Oct
(11
:
4)
10
82% yield
9
PhI
Pd(dppf)Cl
2
KOH
B
Ph
3
(11
:
5)
n
11,
n=1
12,
n=2
n
13,
n=1, 65%
14,
n=2, 55%
The second challenge for the successful coupling of secondary organo-
boranes is the propensity of secondary alkyl transition metal complexes to
undergo b-hydride elimination.
8,18-20
The overall consequences of this side-
reaction are the loss of organic groups upon reductive elimination with the
hydride generated or conversely the readdition of the hydride to give a linear
alkyl substituent and subsequent coupling to provide the undesired, linear
product, 17 [eqn (11.6)].
21
In cyclic symmetrical systems, such addition/
elimination sequences are invisible and therefore diculties only appear
when chiral or unsymmetrical substrates are employed.
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