Synthesis of 4-substituted homoallylic alcohols via a one-pot tandem Lewis-acid catalyzed crotylboration-[3,3]-sigmatropic rearrangement

Article abstract of DOI:10.1039/b418996e

Crotylboration of aldehydes with E- or Z-crotylboronates in the presence of catalytic amounts of indium triflate provides the corresponding 4-substituted homoallylic alcohols. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b418996e

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Synthesis of 4-substituted homoallylic alcohols via a one-pot tandem
Lewis-acid catalyzed crotylboration-[3,3]-sigmatropic rearrangement
P. Veeraraghavan Ramachandran,* Debarshi Pratihar and Debanjan Biswas
Received (in Cambridge, UK) 20th December 2004, Accepted 3rd February 2005
First published as an Advance Article on the web 18th February 2005
DOI: 10.1039/b418996e
Crotylboration of aldehydes with E- or Z-crotylboronates in
the presence of catalytic amounts of indium triflate provides the
corresponding 4-substituted homoallylic alcohols.
We accounted for the formation of the rearranged borate
intermediate II via a similar sigmatropic rearrangement of the
borate intermediate I derived from initial crotylboration. A slight
excess of aldehyde is necessary for this conversion as elucidated
in Scheme 2. Indeed, crotylborations are typically carried out with
1.2 equiv. of aldehyde.
Crotylboration using various allylboronates leads to the formation
of 2-substituted homoallylic alcohols, which are important units
for the synthesis of various biologically active complex natural
After careful investigation of the effect of temperature and
equivalents of aldehyde on Lewis acid-catalyzed crotylboration,
we extended our study to a variety of aldehydes. Crotylboration
of hexanaldehyde with (E)-crotylboronate 3b was complete within
45 min, with the corresponding a-adduct 6b being formed
predominantly. The stereochemistry of the reagent was exclusively
transferred to the product. [(E)-reagent to (E)-adduct] (Table 1,
entry 6). A similar result was obtained with (Z)-crotylboronate
(Table 1, entry 2). Isobutyraldehyde provided the rearranged
products 7a and 7b, albeit in poor yields, with (Z) and
1
products. This reaction has been well studied for the ready access
2
of this class of compounds. Herein we report a controlled in situ
conversion of aldehydes to 4-substituted homoallylic alcohols via
Lewis acid-catalyzed crotylboration.
Recently, we reported the room and high temperature
allylboration of aldehydes with functionalized allylboronates for
3
the preparation of a-methylene-c-butyrolactones 1 [eqn. (1)]. To
accelerate the reactions at lower temperatures, we were examining
4
the effect of Lewis acid catalysis. During this process, we observed
the formation of a-alkylidine-c-butyrolactones 2 as the major
5
products [eqn. (1)].
ð1Þ
This unexpected reaction prompted us to examine the Lewis
6
acid-catalyzed crotylboration of aldehydes with crotylboronates.
We examined In(OTf) , Sc(OTf) , Yb(OTf) , Zn(OTf) , ZnCl ,
3
3
3
2
2
SnCl , and MgCl as possible Lewis acids and found that In(OTf)
3
4
2
gave the best results. Our initial investigation revealed that
Scheme 1
crotylboration of benzaldehyde at 278 uC with both (Z)- and
(E)-crotylboronate (3a and 3b) in the presence of 10% In(OTf)
3
provided the expected 2-substituted homoallylic alcohols 4a and 4b
respectively. However, when the same reaction was carried out
at room temperature, the corresponding 4-substituted homoallylic
alcohols, 5a and 5b respectively, were obtained with very high
regioselectivity. Conversion of 2-substituted homoallylic alcohols to
the corresponding 4-substituted derivatives via a [3,3]-sigmatropic
7
rearrangement was, recently, independently reported by Nokami
8
and Loh and their co-workers.
When the reaction was carried out at room temperature with
0.8 equiv. of the aldehyde, we obtained a 4:1 ratio of 4a and 5a,
with 4a as the major product. Thus, we have demonstrated that,
at will, we can obtain 2-substituted or 4-substituted homoallylic
alcohols via crotylboration either by changing the reaction tem-
perature or by changing the equivalents of the aldehyde at room
temperature (Scheme 1).
*chandran@purdue.edu
Scheme 2
1
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Table 1 Preparation of 4-substituted homoallylic alcohols
observed). The solution was then washed with sat. NH
and extracted with ether (3 6 5 mL). The combined organic layer
was then washed with brine, dried over anhydrous MgSO , and
4
Cl (2 mL)
4
concentrated under reduced pressure. The crude product was then
purified by column chromatography (silica gel, hexanes:ethyl
acetate: 95:5) to obtain 4a or 4b.
Allylboration at room temperature: 3a or 3b (1 mmol) was
3
dissolved in toluene. In(OTf) (0.12 mmol) was added to the above
9
solution at room temperature followed by the addition of aldehyde
Entry Reagent
R
Time (min) Product Yield (%) E:Z
(
1.2 mmol) and the reaction mixture was stirred at room
11
1
2
3
4
5
6
7
8
3a
3a
3a
3a
3b
3b
3b
3b
Ph 15
n-Pent 25
5a
6a
7a
8a
5b
6b
7b
8b
87
65
30
65
90
70
30
96
,1:.99
,1:.99
,1:.99
,1:.99
.99:,1
.99:,1
.99:,1
.99:,1
temperature until the reaction was complete (monitored by
B
NMR: crotylboronate peak at d 33 ppm disappeared and a peak
at d 22 ppm was observed). The solution was then washed with sat.
i-Pr
Cy
Ph
150
210
15
NH
combined organic layer was then washed with brine, dried over
anhydrous MgSO , and concentrated under reduced pressure. The
4
Cl (2 mL) and extracted with ether (3 6 5 mL). The
n-Pent 45
i-Pr
Cy
120
180
4
crude product was then purified by column chromatography (silica
gel, hexanes:ethyl acetate: 95:5) to obtain 5a–8a or 5b–8b.
(E)-crotylboronate respectively (Table 1, entries 3 and 7). We are
currently examining the low yields. Crotylboration of cyclohexane
P. Veeraraghavan Ramachandran,* Debarshi Pratihar and
Debanjan Biswas
Herbert C. Brown Center for Borane Research, Department of
Chemistry, Purdue University, 560 Oval Drive, West Lafayette,
Indiana 47907, USA. E-mail: chandran@purdue.edu
carboxaldehyde with (E)-crotylboronate 3b provided the a-adduct
8
9
b in 96% yield and .99% E-selectivity. (Table 1, entry 8). The
corresponding Z-product 8a was obtained in 65% yield with high
selectivity.
In conclusion, we have described the first example of an in situ
Notes and references
In(OTf)
of 4-substituted homoallylic alcohols via a tandem crotylboration-
3,3]-sigmatropic rearrangement in the presence of a slight excess of
3
-catalyzed crotylboration of aldehydes for the preparation
1
(a) A. B. Smith, C. M. Adams, S. A. L. Barbosa and A. P. Degnan,
J. Am. Chem. Soc., 2003, 125, 350; (b) D. T. Hung, J. B. Nerenberg and
S. L. Schreiber, J. Am. Chem. Soc., 1996, 118, 11054; (c) J. D. White,
P. R. Blakemore, N. J. Green, E. B. Hauser, M. A. Holoboski,
L. E. Keown, C. S. N. Kolz and B. W. Phillips, J. Org. Chem., 2002, 67,
[
aldehydes. The chiral variant of this reaction is under investigation.
A typical procedure for the crotylboration-rearrangement
7750; (d) R. S. Coleman, J. Li and A. Navarro, Angew. Chem. Int. Ed.,
of aldehydes with 3a or 3b is as follows. Preparation of
t
Z)-crotylboronate (3a): KO Bu (1 mmol) was taken up in 2 mL
2001, 40, 1736.
(
2
(a) Y. Yamamoto, Acc. Chem. Res., 1987, 20, 243; (b) Y. Yamamoto and
N. Asao, Chem. Rev., 1993, 93, 2207; (c) R. W. Hoffmann, Pure Appl.
Chem., 1988, 60, 123; (d) R. W. Hoffmann, Angew. Chem., Int. Ed. Engl.,
anhydrous THF and cooled to 278 uC. cis-2-Butene (1.5 mmol)
was condensed in a 278 uC bath and transferred to the reaction
mixture. n-BuLi (2.5 M in hexane, 1 mmol) was then added
dropwise so that the temperature was maintained below 250 uC.
After completion of the addition, the cooling bath was removed
and the reaction mixture was stirred at 250 uC for 30 min. The
solution was then recooled to 278 uC. Triisopropylborate (1 mmol)
was then added dropwise to the (Z)-crotylpotassium solution and
stirred for 30 min at 278 uC. The solution was rapidly poured into
separating funnel containing 10 mL of 1N HCl saturated with
NaCl. A solution of pinacol (1.1 mmol) in 5 mL THF was added
directly to the separating funnel. The two phases were separated
and the aqueous layer was extracted with ether (3 6 10 mL). The
1987, 26, 489; (e) W. R. Roush, ACS Symp. Ser., 1989, 386, 242; (f)
W. R. Roush, in Houben–Weyl Methods of Organic Chemistry, ed.
G. Helmchen, R. W. Hoffmann, J. Mulzer and E. Schaumann, Georg
Thieme Verlag, Stuttgart, 1995, vol. E21, p. 1410; (g) W. R. Roush,
in Comprehensive Organic Synthesis, ed. B. M. Trost and I. Fleming,
Pergamon Press, Oxford, 1992, vol. 2, pp. 1–53; (h) H. C. Brown and
P. V. Ramachandran, J. Organomet. Chem., 1995, 500, 1.
3 P. V. Ramachandran, D. Pratihar, D. Biswas and A. Srivastava, Org.
Lett., 2004, 6, 481.
4
T. Ishiyama, T. Ahiko and N. Miyaura, J. Am. Chem. Soc., 2002, 124,
2414.
1
5
6
P. V. Ramachandran, D. Pratihar and D. Biswas, unpublished results.
Crotyldialkylboranes are extremely reactive and do not need catalysts.
We also observed that they do not undergo the reaction discussed herein.
(a) J. Nokami, K. Yoshizane, H. Matsuura and S. Sumida, J. Am. Chem.
Soc., 1998, 120, 6609; (b) S. I. Sumida, M. Ohga, J. Mitani and
J. Nokami, J. Am. Chem. Soc., 2000, 122, 1310; (c) J. Nokami,
L. Anthony and S. I. Sumida, Chem. Eur. J., 2000, 6, 2909; (d) J. Nokami,
K. Nomiyama, S. Matsuda, N. Imai and H. Kataoka, Angew. Chem. Int.
Ed., 2003, 42, 1273–1275.
7
8
9
combined organic layer was dried over anhydrous MgSO and was
4
concentrated under vacuum to obtain the (Z)-crotylboronate (3a)
in .99% isomeric purity.
(E)-Crotylboronate (3b) was obtained in .99% isomeric purity
from trans-2-butene by using an identical procedure as above.
(a) T. P. Loh, K. T. Tan, J. Y. Yang and C. L. Xiang, Tetrahedron Lett.,
Allylboration at 278 uC: 3a or 3b (1 mmol) was dissolved in
toluene. In(OTf) (0.12 mmol) was added to the above solution
3
2
001, 42, 8701; (b) T. P. Loh and J. R. Zhou, Tetrahedron Lett., 2000, 41,
5261; (c) C. L. K. Lee, C. H. A. Lee, K. T. Tan and T. P. Loh, Org. Lett.,
004, 6, 1281; (d) T. P. Loh, K. T. Tan and Q. Y. Hu, Angew. Chem. Int.
2
and the solution was cooled to 278 uC. Aldehyde (1.2 mmol) was
added and the reaction mixture was stirred at 278 uC until the
reaction was complete (monitored by B NMR: crotylboronate
Ed., 2001, 40, 2921; (e) K. T. Tan, S. S. Ching, H. S. Cheng and T. P. Loh,
J. Am. Chem. Soc., 2003, 125, 2958.
1
Only one isomer was detected in the H NMR spectrum of the crude
sample.
11
peak at d 33 ppm disappeared and a peak at d 22 ppm was
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Chem. Commun., 2005, 1988–1989 | 1989