Chemistry Reference
In-Depth Information
N
N
O
O
Li
B(OR)
2
B(OR)
2
chiral amine,
s
BuLi,
- 78°C
1.
N
i
Pr
2
O
N
i
Pr
2
R
R
O
R
2. MgBr
2
Et
2
O, 38 °C
80a,b
i
81a,b
80a
, R = alkyl, chiral amine = Sparteine,B(OR)
2
= BPin, ee
95%
80b
, R = aryl, chiral amine = bisoxazoline
82
, B(OR)
2
= Bneop, ee 80-98%
≥
O
O
N
N
82
Scheme 11.8
Synthesis of optically enriched boronic esters 81a and 81b.
intermediate i with the boronic ester, this leads to re-equilibration back to i
at higher temperature and resulting racemization. However, consistent with
reports from Aggarwal et al. in other systems sensitive to racemization,
58
it
was found that employing less hindered neopentyl boronic esters along with
a bis-oxazoline ligand
59
in place of the typical sparteine ligand in addition to
the smaller neopentyl diol-derived boronate ester led to high enantioselec-
tivities (Scheme 11.8).
57
Once the synthesis of the starting boronic esters was developed, the
coupling reaction proceeded with good to excellent enantiospecificities
[eqn (11.19)], typically on the order of 90-100%. Consistent with related
chemistry, the Suzuki-Miyaura cross-coupling proceeded with retention of
configuration.
57
(11
:
19)
82
83
An outlier in terms of the requirement for silver(I) oxide in the coupling of
secondary boronic ester derivatives, homoallylic boronic esters also undergo
coupling in the specific case where there is activation by an internal base.
60
Thus, Masaki and Suginome demonstrated that 84a and 84b undergo
coupling with aryl iodides in the presence of typical Pd catalysts and bases
with retention of configuration (Scheme 11.9). Interestingly, the corres-
ponding O-acetylated BPin derivatives (86a and 86b) are inert under identical
conditions, demonstrating the importance of the specific substituents on
boron in this case.
60
The final class of substrate that has been demonstrated to undergo ste-
reoretentive coupling is benzylic ethers. In 2012, Molander's group reported
that enantioenriched benzyl ethers 87 substituted at the a-position with a
BF
3
K group undergo stereoretentive Suzuki-Miyaura coupling [eqn (11.20)].
61
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