Electronic effects in asymmetric hydroboration

Article abstract of DOI:10.1016/S0040-4039(02)02013-0

To determine whether electronic effects are operative in asymmetric hydroboration, a series of para-substituted 2-aryl-1-propenes were prepared and reacted with four asymmetric borane reagents. A significant correlation between the electronic nature of the para-substituent and the degree of asymmetric induction was observed only for a chloroborane-ether complex, not for any of several simple alkylboranes. A quantitative analysis of the relative reactivities is also given.

Full text of DOI:10.1016/S0040-4039(02)02013-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 8339–8342
Electronic effects in asymmetric hydroboration
Charles M. Garner,* Shirley Chiang, Matthew Nething and Robert Monestel
Department of Chemistry, Baylor University, Waco, TX 76798, USA
Received 9 July 2002; accepted 13 September 2002
Abstract—To determine whether electronic effects are operative in asymmetric hydroboration, a series of para-substituted
-aryl-1-propenes were prepared and reacted with four asymmetric borane reagents. A significant correlation between the
2
electronic nature of the para-substituent and the degree of asymmetric induction was observed only for a chloroborane–ether
complex, not for any of several simple alkylboranes. A quantitative analysis of the relative reactivities is also given. © 2002
Elsevier Science Ltd. All rights reserved.
The chemoselectivity, regioselectivity and stereospecific-
ity of hydroboration has made it one of the more useful
reactions in organic synthesis. Asymmetric variants of
asymmetric hydroboration of a series of para-substi-
tuted 2-arylpropenes (1). These were generally prepared
via a Grignard reaction as shown in Scheme 1.
1
this reaction have made a variety of compounds, espe-
cially secondary alcohols, available in high enan-
For the asymmetric hydroboration reactions, we chose
the three most widely-used chiral boranes: diisopino-
2
tiomeric purity. The effect of structural variations in
3
4
10
the alkene on reactivity, regiochemistry and (for
asymmetric hydroboration) asymmetric induction have
campheylborane (IPC BH, 2), mono-isopinocamphyl-
2
1
1
borane (IPCBH , 3), and dilongifolylborane (Lgf BH,
2
2
2
12
been well studied. Likewise, electronic effects on both
4) (Scheme 2). In addition, we also employed the
5
6
reactivity and regiochemistry have been studied. How-
ever, there appears to have been no systematic study of
how purely electronic effects influence the degree of
readily-available but less well-known crystalline
13
chloroborane complex 5. To analyze the optical
purities of the products, we found that direct analytical
separation of the 2-aryl-1-propanol enantiomers (6)
was possible using a chiral GC separation (discussed
later).
7
asymmetric induction observed. Indeed, the assump-
tion seems to have been that in all enantioselective
reactions steric factors are paramount, and electronic
8
effects have rarely been studied. A study of asymmetric
hydroboration of a series of heterocyclic alkenes has
been reported, but this necessarily involved changing
both sterics and electronics simultaneously.
The asymmetric hydroboration of the 1-arylpropenes
(1) with the chiral boranes were carried out at constant
temperature (30°C) in either THF or (for chloroborane
9
5
) benzene, with the exception of (IPC) BH which was
2
To fully separate any steric effects from electronic
effects, we undertook a classical Hammett study of the
carried out at 0°C in THF (Scheme 3). All the asym-
metric hydroboration reactions were carried out at least
Scheme 1.
*
0
Corresponding author.
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02013-0

8
340
C. M. Garner et al. / Tetrahedron Letters 43 (2002) 8339–8342
Scheme 2.
Scheme 3.
twice, and the reactions with chloroborane carried out
in pairwise combinations with an internal standard
The presence of electronic effects were evaluated by the
linearity and slope of a Hammett plot between log
18
"
which allowed determination of the relative rates by
GC analysis after oxidation. Oxidation with H O and
(enantiomer ratio) (which is proportional to DG , the
difference in activation energies leading to each enan-
2
2
1
4
16
alcoholic KOH cleanly gave 2-aryl-1-propanols (6) as
well as the oxidized residue (7) of the borane reagent.
The presence of 2-aryl-2-propanols was not detected by
GC. In no case were we able to observe the alcohol
from the dimethylamino-substituted alkene; it is possi-
ble that coordination between the amino group and the
borane rendered the latter unreactive under these con-
ditions. Probably because the chiral center is one car-
bon removed from the OH group, standard methods of
optical purity analysis (e.g. chiral shift NMR or conver-
sion to diastereomeric derivatives followed by NMR or
GC analysis) gave ambiguous results with respect to the
enantiomer ratio and/or the absolute configuration of
the major product. However, chiral GC analysis using a
tiomer) and sigma-para. None of the three simple
alkylboranes studied (mono- and di-isopinocamphyl-
borane, and dilongifolylborane) showed a significant
electronic effect; in all these cases there was significant
2
scatter (r =0.01–0.3) and the slope of the least-squares
line was very shallow (0.01–0.15). However, in the case
of chloroborane 5 there was a significant electronic
effect observed (see Fig. 1), the least-squares line corre-
2
lating well (r =0.95) and a significant slope was
observed (−0.48). The electron-rich alkenes gave dis-
tinctly higher levels of asymmetric induction than elec-
tron poor alkenes.
We had anticipated that the electron-poor alkenes (i.e.
Z=electron-withdrawing) would react the most slowly
but give the ‘tightest’ transition state (i.e. closest
approach between the borane and the alkene) and thus
give the highest asymmetric induction. This would be
consistent with the general principle of higher reactiv-
ity/lower selectivity that is often observed in a variety
of reactions, and this behavior has been observed in the
diastereoselective metal-catalyzed hydroboration of
15
Cyclosil-B column was successful, giving adequate
separation between enantiomers (resolution=0.65–1.2),
with the (R) enantiomer eluting first. In all cases, the
alcohol residue from the chiral borane reagent was
longer retained than any of the 2-aryl-1-propanols on
the GC and did not interfere. The GC analysis was
repeated three times on each sample; the run-to-run
standard deviation on the % ee was generally less than
7
1% ee. The results are given in Table 1; negative values
allylic alcohol derivatives. However, we observe
indicate that the (R) enantiomer predominated.
exactly the opposite with chloroborane 5: the p-chloro
Table 1. Enantiomeric excesses observed in the asymmetric hydroboration/oxidation of a series of p-substituted 1-arylprope-
nes 1. Positive values indicate that the (S) enantiomer predominated
Z group (sigma)16
(IPC) BH
IPCBH2
(Lgf) BH
Chloroborane 5
Relative rate with chloroborane 5
2
2
CF3 (0.53)
Cl (0.24)
F (0.15)
H (0.0)
CH3 (−0.14)
OCH3 (−0.12)
14
13
9
3
11
17
13
9
−4
−8
−0.5
7
17
10
13
19
16
18
−5.6
4
16
26
26
0.15
0.29
0.58
1
2.2
3.8
30

C. M. Garner et al. / Tetrahedron Letters 43 (2002) 8339–8342
8341
Figure 1. Hammett plot for asymmetric hydroboration of para-substituted a-methylstyrenes with chloroborane 5.
alkene (|=0.24) gave nearly racemic product (0.5% ee),
ration reactions of 5 were carried out pairwise, and we
were able to determine the relative reactivities of the
various alkenes using the Ingold–Shaw equation. The
16
while the p-methyl compound (|=−0.14) gave 30%
1
8
ee. Based on relative retention times and a previous
1
7
study of a-methylstyrene, the major enantiomer in all
relative reactivity (last column in Table 1) correlates
5
cases (except for CF ) is of the (S) configuration. An
well with sigma-p (see Fig. 2), and as expected, alkenes
3
interesting observation is that the strongest electron-
containing the more electron-withdrawing groups are
less reactive.
withdrawing group (i.e. CF , |=0.53) gives the oppo-
3
site enantiomer (R) as the major product. To our
knowledge, there have been no reports of a change in
the sense of asymmetric induction based on electronic
effects alone. However, studies of electronic effects in
asymmetric epoxidation reactions have also shown the
degree of asymmetric induction to correlate with
This study establishes for the first time the operation of
purely electronic effects in asymmetric hydroboration,
as well as revealing an interesting dependence on
borane electronics (i.e. chloroborane–ether complex
versus simple alkylboranes) which may be of value in
the design of new asymmetric reagents. Whether these
electronic effects in chloroborane 5 are observed
because of the presence of the chlorine or because of
the internal coordination remains to be determined.
8
increasing electron donating character. The hydrobo-
Acknowledgements
We thank the Robert A. Welch Foundation for partial
support of this work.
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