3
Initially, we were concerned whether sulfone 1 would
remain intact under the acidic conditions used for its analog 5.
We thought that the boronic ester might be deborylated under
these conditions. However, it turned out that boronic ester 1 is
stable in acetic acid at 95 C. In general, alkyl substrates could
be isomerized to the more thermally stable olefins and isolated
products were recovered with the boronic ester intact (Table
This procedure is convenient, yet is not as stereoselective
as the metathesis procedure and further work will be necessary
to enhance stereoselectivity. However, the methodology could
find good use in certain contexts, as exemplified below.
o
We are interested in using functionalized boronates as
lynchpins in the preparation of polycyclic systems. To that
end, boronate 9 was deprotonated and alkylated with triflate
1
).
Substrate 2b was found to undergo isomerization
1
0, affording 11 in 73% yield. An intramolecular Suzuki
uneventfully to form 8b in 89% yield (entry 1). However, this
and other examples exhibited little stereoselectivity, as the
product was produced as a 2.7:1 mixture of Z:E isomers,
respectively. Substrate 2d underwent desilylation rather than
simple isomerization, though it is not clear if isomerization
preceded desilylation (entry 3). Substrate 2e formed 8e
smoothly in excellent yield (entry 4).
5
coupling using a procedure developed by Kishi afforded a 1:1
mixture of products 13 and 13’. In an effort to circumvent the
formation of isomers, compound 11 was isomerized to 12 in
4% yield using the procedure detailed herein. Intramolecular
Suzuki coupling afforded 13’ as the sole product in 90%
6
isolated yield.
In summary, we have shown that borylated allylic sulfones
can be isomerized under mildly acidic conditions to their more
stable counterparts. For acyclic systems, the stereoselectivity
is low. However, a single example of isomerization in a cyclic
system demonstrated the utility of the method. Further studies
are in progress. Results will be reported in due course.
The stereochemistry of the major isomerized products was
determined via Nuclear Overhauser Effect Spectroscopy
(
NOESY). As a representative example, a portion of the two-
1 1
dimensional H- H NOESY spectrum for the diastereomeric
mixture of 8g is shown in Figure 1. The triplets appearing
between 6.0 - 7.0 ppm on the horizontal axis correspond to the
vinylic protons of 8g, H and H , and the singlets around ~ 4
a
b
Acknowledgments
ppm on the vertical axis correspond to the α-sulfonyl protons.
The vinylic hydrogen that is spatially close to α-sulfonyl
hydrogens displays an overlap signal on the two-dimensional
spectra, corresponding to the E isomer. The absence of any
signal at the intersection of the two red lines verifies that the
This work was sponsored by the US National Science
Foundation and the Department of Chemistry at the University
of Missouri-Columbia. We thank Frontier Scientific for a gift
of starting material used in the synthesis of 1. We thank Ms.
Carissa S. Hampton (University of Missouri-Columbia) for
assistance in preparing this manuscript.
isomer in larger population, H , corresponds to the Z isomer.
a
References and notes
1
2
.
.
Altenhofer, E. F.; Harmata, M. Chem. Commun. 2013, 49,
365.
However, see: (a) Whiting, A. Tetrahedron Lett., 1991, 32,
2
1
1
1
503. (b) Curtis, A. D. M. ; Whiting, A. Tetrahedron Lett.,
991, 32, 1507. (c) Mears, R. J.; Whiting, A. Tetrahedron,
993, 49, 177. (d) Curtis, A. D. M. ; Mears, R. J.; Whiting, A.
Tetrahedron, 1993, 49, 187.
3
4
.
.
Altenhofer, E.; Harmata, M. Org. Lett. 2014, 16, 3-5.
Knight, D. J.; Lin, P.; Whitham, G. H. J. Chem. Soc., Perkin
Trans. 11987, 2707.
5
.
Uenishi, J.; Beau, J-M.; Armstrong, R. W.; Kishi, Y. J. Am.
Chem. Soc. 1987, 109, 4756.
Supplementary Material
Supplementary material associated with this article can be
found in the online version at: http://dx.doi.org/……
Figure 1. NOESY spectrum of E/Z-8b.
Altenhofer, Erich
