Synthesis of tri-substituted vinyl boronates via ruthenium-catalyzed olefin cross-metathesis

Article abstract of DOI:10.1016/j.tetlet.2004.08.069

Tri-substituted vinyl pinacol boronates are synthesized using cross-metathesis of α-substituted vinyl boronates. The reactions proceed with moderate yields and high Z-selectivity when R¹ = methyl. When R¹ is larger than a methyl group, yields and Z-selectivity are moderate at best, and the reactions are highly substrate dependent.

Full text of DOI:10.1016/j.tetlet.2004.08.069

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 7733–7736
Synthesis of tri-substituted vinyl boronates via ruthenium-catalyzed
olefin cross-metathesis
Christie Morrill, Timothy W. Funk and Robert H. Grubbs*
Contribution from the Arnold and Mabel Beckman Laboratory of Chemical Synthesis, Division of Chemistry and
Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Received 31 July 2004; accepted 12 August 2004
Abstract—Tri-substituted vinyl pinacol boronates, which are key reactive intermediates in a variety of transformations, are synthe-
sized using ruthenium-catalyzed olefin cross-metathesis of a-substituted vinyl boronates and various alkenes. Cross-metathesis of 2-
isopropenyl pinacol boronate proceeds with moderate yield and high Z-selectivity when sterically unhindered cross partners are
used. Cross-metathesis of vinyl boronates that possess a-substitution larger than a methyl group is also achieved. Yield and Z-selec-
tivity are lower in these cases, and the success of a cross-metathesis reaction is highly dependent on the steric bulk surrounding the
double bond of the a-substituted vinyl boronate.
Ó 2004 Elsevier Ltd. All rights reserved.
Vinyl boronates are important intermediates in organic
synthesis.1 The boronate moiety can be converted into
various functionalities such as hydrogen,1c an aldehyde
or ketone,1c,2 a halide,3 an amine,2 or an alkyl group.4
Most notably, these compounds are excellent compo-
nents in Suzuki cross-coupling reactions.5 Vinyl boro-
nates are most commonly synthesized using alkyne
hydroboration.1c,6 While this method usually works well
when forming 1,2-disubstituted vinyl boronates from
terminal alkynes, the formation of tri-substituted vinyl
boronates from unsymmetrical, internal alkynes is more
difficult to achieve due to lack of regioselectivity in the
hydroboration reaction.7 Desirable results are only ob-
tained when the two substituents on the starting alkyne
are significantly different in steric bulk, and even then
these results are highly dependent on the reaction condi-
tions and the boron source.8
Because cross-metathesis lacks the regioselectivity issues
that arise in hydroboration reactions, it offers an attrac-
tive alternative for the synthesis of tri-substituted vinyl
boronates. In addition, alkenes are more desirable start-
ing materials than alkynes, because alkynes are often
more challenging to install in a molecule14 and are inher-
ently more reactive than alkenes.15 A variety of func-
tionalized 1,2-disubstituted vinyl boronates were
prepared using cross-metathesis catalyzed by 2.16 As dis-
cussed below, cross-metathesis of a-substituted vinyl
boronates provides a route to selected tri-substituted
vinyl boronates.
Olefin cross-metathesis has become a viable synthetic
strategy for the synthesis of highly functionalized alke-
nes,9,10 due to the development of ruthenium catalysts
such as 111 and 2.12 The more active catalyst, 2, can
be used to synthesize tri-substituted olefins.13
The initial studies examined the cross-metathesis of 2-
isopropenyl pinacol boronate (3).17 The results of these
reactions are given in Table 1.18 Tri-substituted vinyl
boronates were obtained in moderate yield (ca. 60%)
when relatively unhindered cross partners were used
(entries 1–3). Unfortunately the product yield dropped
significantly when more hindered cross partners were
used (entries 4–6). Even a methyl group in the a-position
Keywords: Olefin cross-metathesis; Vinyl boronates; Tri-substituted
alkenes; Ruthenium catalysis.
*
Corresponding author. Tel.: +1 6263953470; fax: +1 6265649297;
e-mail: rhg@caltech.edu
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.08.069

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C. Morrill et al. / Tetrahedron Letters 45 (2004) 7733–7736
Table 1. Cross-metathesis of 3 with various alkenesa
Entry
1
Cross partner
Equiv
0.5
Cross product
Isolated yield (%)
58
Z:Eb
O
B
>20:1
Me
AcO
O
AcO
4
O
B
Me
R3Si
O
2a (R = i-Pr)
2b (R = Me)
1
1
59
59
>20:1
>20:1
R3Si
5a,b
O
B
Me
O
3
4
1
2
46
30
>20:1
>20:1
BzO
BzO
6
O
B
Me
O
7
O
B
Me
BzO
O
OBz
O
5
6
0.5
1
30
2:1
8c
BzO
9
—
N.R.
—
O
a (1equiv 3) 5mol% 2, 0.2M in CH2Cl2, reflux, 12h, 0.2–0.4mmol scale.
b Determined by 1H NMR.
c Z:E = 16:1.
of an alkenyl boronate makes the substrate much more
challenging for cross-metathesis than both vinyl and 1-
propenyl boronate.16 Although the yields were moder-
ate, in most cases the cross-metathesis of 3 proceeded
with high Z-selectivity. The tri-substituted vinyl boro-
nate products shown in Table 1 would be challenging to
synthesize regioselectively using alkyne hydroboration.
selectivity in these reactions was only moderate as well,
although the E- and Z-isomers could be separated by
column chromatography, allowing the isolation of each
stereoisomer.
Examination of the results shown in Table 2 reveals that
the success of these cross-metathesis reactions is extre-
mely dependent on the steric bulk surrounding the dou-
ble bond of the a-substituted vinyl boronate starting
materials. For example, when the a-substituent is an
alkyl chain with a bulky silyloxy group at the end,
decreasing the number of methylene units in the chain
from three to two reduces the cross-metathesis yield by
about half (Table 2, compare entries 2 and 3c). Further-
more, when the alkyl chain is reduced to only a single
methylene unit, no cross-metathesis is observed (Table
2, entry 4c). Cross-metathesis yields also vary widely
when the protecting groups are changed. For example,
Vinyl boronates possessing a-substitution that was
larger than a methyl group were synthesized in moder-
ate-to-high yield according to the general procedure
illustrated in Scheme 1.19,20 Table 2 shows the results
of the cross-metathesis reactions using these larger sub-
strates. Unfortunately these a-substituted boronates
were even more challenging substrates for cross-meta-
thesis than boronate 3, and thus the yields in these reac-
tions were moderate at best, with several substrates
exhibiting no cross-metathesis activity at all. The Z-
Scheme 1.

C. Morrill et al. / Tetrahedron Letters 45 (2004) 7733–7736
Table 2. Cross-metathesis of a-substituted vinyl boronates with 5-hexenyl acetatea
7735
Entry
a-Substituted vinyl boronate
Equiv
Cross product
Isolated yield (%)
Z:Eb
O
O
B
1
2
40
54c
3:1
4:1c
B
O
O
AcO
10
11
O
B
O
B
O
O
2
1.2
TBSO
35
4:1
O
TBSO
AcO
12
13
O
B
O
B
RO
RO
3a (R = OH)
3b (R = OAc)
3c (R = OTBS)
2
N.R.
N.R.
17
—
—
5:1
O
2
1.3
AcO
14a,b,c
15c
O
B
O
B
O
4a (R = OH)
4b (R = OAc)
4c (R = OTBS)
2
2
2
N.R.
40
N.R.
—
1:1
—
RO
O
RO
AcO
16a,b,c
17b
O
B
5
2
—
N.R.
—
O
a (1equiv 5-hexenyl acetate) 5mol% 2, 0.2M in CH2Cl2, reflux, 12h, 0.2–0.4mmol scale.
b Determined by 1H NMR.
c 20mol% 2.
in entry 4 of Table 2, the cross-metathesis product is iso-
lated in 40% yield when the a-substituent of the vinyl
boronate contains an acetate group (16b), but no
cross-metathesis is observed when the acetate is replaced
with a t-butyldimethylsilyloxy group (16c). These obser-
vations have led us to conclude that a metathesis cata-
lyst that is more tolerant of sterically bulky olefins is
needed in order for cross-metathesis of a-substituted
vinyl boronates to provide a general route to tri-substi-
tuted vinyl boronates.
extremely useful in organic synthesis. Both the yields
and the stereoselectivities in these reactions have room
for improvement, which we believe can be achieved
through the development of new metathesis catalysts.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2004.08.069. Information available: Experimental pro-
cedures and characterization for 4–7 and 9–17.
Cross-metathesis of a-substituted vinyl boronates can be
used to generate tri-substituted vinyl boronates. When
the a-substituent is a methyl group, the cross-metathesis
products can be isolated in moderate yields (ca. 60%)
and possess almost entirely Z-geometry as long as
sterically unhindered cross partners are used. Cross-
metathesis products can also be isolated when vinyl bor-
onates possessing a-substitution larger than a methyl
group are used. However, in these cases the yields and
stereoselectivity drop significantly (ca. 40% yield and
Z:E = 4:1 at best), and the success of a cross-metathesis
reaction is highly substrate dependent. Most of the tri-
substituted vinyl boronates reported in this paper would
be difficult or impossible to generate regioselectively
using conventional hydroboration procedures, and thus
this cross-metathesis procedure has the potential to be
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