Alkylation of aldehydes with trialkylboranes in water

Article abstract of DOI:10.1002/adsc.200606136

Water enables the alkylation of aldehydes with trialkylboranes under nickel catalysis without the addition of a base. Trialkylboranes prepared from borane-dimethyl sulfide and terminal olefins via hydroboration as well as commercially available trialkylboranes could be employed for the reaction. The reaction would proceed via η²-coordinated nickel complexes with aldehydes as the key intermediates.

Full text of DOI:10.1002/adsc.200606136

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DOI: 10.1002/adsc.200606136
Alkylation of Aldehydes with Trialkylboranes in Water
Koji Hirano,a Hideki Yorimitsu,a,* and Koichiro Oshimaa,*
a
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto-daigaku Katsura,
Nishikyo-ku, Kyoto 615-8510, Japan
Fax : +81-75-383-2438; e-mail: yori@orgrxn.mbox.media.kyoto-u.ac.jp or oshima@orgrxn.mbox.media.kyoto-u.ac.jp
Received: March 24, 2006; Accepted: May 15, 2006
Abstract: Water enables the alkylation of aldehydes
with trialkylboranes under nickel catalysis without
the addition of a base. Trialkylboranes prepared
from borane-dimethyl sulfide and terminal olefins
via hydroboration as well as commercially available
trialkylboranes could be employed for the reaction.
The reaction would proceed via h2-coordinated
nickel complexes with aldehydes as the key inter-
mediates.
nickel has become available. This advantage promot-
ed us to develop the alkylation of aldehydes with tri-
alkylboranes by nickel catalysis in water. Here we
report the results of the alkylation in water and the
unique effect of water as a solvent in the alkylation
reaction.
We first examined the ethylation and butylation of
benzaldehyde (1a) (Scheme 1 and Scheme 2). Treat-
ment of 1a (0.50 mmol) with triethylborane (2a,
[9]
1.0 mmol) in the presence of 8 mol% of Ni
A
Keywords: aldehydes; alkylation; cyclodextrin;
nickel; trialkylboranes; water
and 19.2 mol% of P(t-Bu)3 in degassed water (20 mL)
A
at room temperature for 20 h provided the corre-
spondingsecondary alcohol 3a in 81% yield. It is
worth notingthat 1a, 2a, and the nickel catalyst were
completely insoluble in water, and the reaction pro-
ceeded in a biphasic system, organic particles in
water. On the other hand, 1a was converted to 3a in
Water is an interestingsolvent in oragnic synthesis
due to its cheap, non-toxic, and non-flammable prop- moderate yield in degassed toluene. The addition of
erties. Therefore, the use of water instead of an or-
ganic solvent has attracted significant attention in the
view points of economy and green chemistry. In addi-
tion, synthetic reactions that are unique in water have
been developed[1] since the extraordinary effect of
water as a solvent was observed in the pericyclic pro-
cesses of Diels–Alder reactions[2] and Claisen rear-
rangements.[3] The additions of organometallic re-
agents to aldehydes in water have also been widely
explored. Allylation with allylmetals[4] and arylation
or alkenylation with organoboronic acid derivatives in
Scheme 1.
the presence of transition metal catalysts[5] have been
established in aqueous media. However, the alkyla-
tion of aldehydes in water is not a trivial reaction.[6]
This is probably because organometallic reagents
havingalkyl groups, which are effective in the alkyla-
tion of carbonyl compounds, are generally highly re-
active and very sensitive to water.[7] With the aid of
transition metal catalysis, water-tolerant organobor-
anes seem to be good reagents for the alkylation in
water. However, alkyl group transfer from boron to
transition metals is usually difficult.
Recently, we have reported the nickel-catalyzed ad-
dition of trialkylboranes to aldehydes in an organic
solvent with cesium carbonate as an activator.[8] By
this reaction, alkyl group transfer from boron to Scheme 2.
Adv. Synth. Catal. 2006, 348, 1543 – 1546
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Koji Hirano et al.
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Table 2. One-pot hydroboration/alkylation.
an excess amount of cesium carbonate was essential
for a satisfactory yield. In the butylation of 1a with
tributylborane (2b), the effect of water as a solvent
was much more remarkable. The reaction of 1a in tol-
uene without cesium carbonate resulted in no conver-
sion. Other organic solvents such as THF, DMF, and
AcOEt led to the same result. Gratifyingly, use of
water (20 mL) as a solvent improved the yield of the
desired product 4a to 90%. The amount of water also
dramatically influenced the yield. Addition of 3.0
equivs. of water in toluene had no effect. In 5 mL and
10 mL of water, benzaldehyde (1a) underwent butyla-
tion to give the corresponding alcohol 4a in 33% and
63% yield, respectively. These results strongly suggest
that use of water as a solvent would play an important
role in the reaction.
Entry R
Trialkylborane Product Yield
1
2
3
4
n-Bu (5a)
t-Bu (5b)
(CH2)2Ph (5c)
(CH2)6OCO-t-Bu
(5d)
(CH2)6OSiMe2-t-Bu 6e
(5e)
(CH2)6OCH2Ph (5f) 6f
6a
6b
6c
6d
7a
7b
7c
7d
74%
71%
36%
17%
AHCTREUNG
AHCTREUNG
5
6
A
7e
7f
69%
24%
AHCTREUNG
By usingoptimal conditions, we performed the eth-
ylation and butylation of an array of various alde-
hydes in water (Table 1). The reaction of sterically de-
mandingaldehyde 1b proceeded smoothly to furnish 74% yield (entry 1). Bulky substitution on the trial-
the correspondingalcohol 3b in 81% yield. Electron- kylborane at the b position did not prevent the reac-
rich aldehyde 1c was converted to 3c and 4c in moder- tion (entry 2). However, the reaction with tri(4-phe-
ate yields. However, use of the electron-deficient al- nylbutyl)borane (6c) resulted in a moderate yield
dehyde 1d resulted in a low conversion.[10] Aliphatic (entry 3). An ester function was compatible under the
aldehydes as well as aromatic ones participated in the reaction conditions albeit the yield was low (entry 4).
reaction. Dihydrocinnamaldehyde (1e) and cyclohexa- The reaction with a trialkylborane havinga silyl ether
necarbaldehyde (1f) underwent ethylation without moiety proceeded smoothly to produce the corre-
difficulties to afford the alkylated products in good spondingalcohol 7e (entry 5) while a benzyl ether
yields.
Trialkylboranes prepared from alkenes via hydro-
moiety in 6f decreased the yield (entry 6).
We are tempted to assume the mechanism for the
boration can be also employed for the reaction alkylation of aldehyde to be as follows (Scheme 3). A
(Table 2). 1-Hexene (5a) was added to a solution of nickel(0) species 8 initially reacts with 1a to generate
borane-dimethyl sulfide in THF and the mixture was the h2-coordinated complex 9 or its resonance form
stirred for 3 h at 08C. Dimethyl sulfide was then re- 10.[11] Subsequent transmetalation of 10 with Et3B or
moved under vacuum (30 torr) at 08C for 1 h. The tri- its aqua complex Et3B·OH2 gives intermediate 11 fol-
hexylborane (6a) obtained was transferred under lowed by reductive elimination to furnish 12 and to
argon to a dispersion of benzaldehyde (1a) and the
nickel catalyst in water at 08C. The mixture was al-
lowed to warm to room temperature and rigorously
stirred for 20 h to furnish 1-phenyl-1-heptanol (7a) in
Table 1. Nickel-catalyzed alkylation of aldehydes with trial-
kylboranes in water.
Entry R1CHO
(R2)3B Product Yield
1
2
3
4
5
6
2-MeC6H4CHO (1b)
4-MeOC6H4CHO (1c) 2a
1c
2a
3b
3c
4c
3d
3e
3f
81%
59%
27%
5%
69%
60%
2b
2a
2a
2a
4-CF3C6H4CHO (1d)
Ph
A
c-C6H11CHO (1f)
Scheme 3.
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Alkylation of Aldehydes with Trialkylboranes in Water
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a degassed hexane solution, 1.0M, 0.096 mL, 0.096 mmol)
were added dropwise. The solution was stirred for 10 min at
08C. Degassed water (20 mL), benzaldehyde (1a, 53 mg ,
0.5 mmol), and Et3B (1.0M hexane solution, 1.0 mL,
1.0 mmol) were then added. The mixture was allowed to
warm to room temperature and stirred for 20 h. The result-
ingmixture was poured into 3.0M hydrochloric acid
(10 mL). Extraction with hexane/ethyl acetate (5:1) followed
by silica gel column purification afforded 1-phenyl-1-propa-
nol (3a); yield: 55 mg(0.41 mmol, 81%).
Synthesis of 4a
In
0.04 mmol) was placed in a reaction flask. THF (0.5 mL)
and P(t-Bu)3 (1.0M hexane solution, 0.096 mL, 0.096 mmol)
a
glovebox filled with argon, Ni(COD)2 (11 mg,
A
AHCTREUNG
were added dropwise. The solution was stirred for 10 min at
08C. Degassed water (20 mL), benzaldehyde (1a, 53 mg ,
0.5 mmol), and n-Bu3B (1.0M THF solution, 1.5 mL,
1.5 mmol) were then added. The mixture was allowed to
warm to room temperature and stirred for 20 h. Extraction
with hexane/ethyl acetate (5:1) followed by concentration
afforded the crude product. The crude product obtained was
oxidized with aqueous H2O2 (30%, 0.8 mL) and aqueous
NaOH (6.0M, 0.5 mL) in EtOH/THF (1.2 mL and 2 mL) at
reflux for 1 h. After aqueous sodium thiosulfate was added,
extraction and purification provided 1-phenyl-1-pentanol
(4a); yield: 74 mg(0.45 mmol, 90%).
Scheme 4.
regenerate 8. Finally, protonolysis of 12 upon work-up
affords alcohol 3a. The effect of water as a reaction
medium is not clear at this stage. Water can enhance
the h2-coordination step and/or the transmetalation
step. These steps cause a reduction of the total
volume of the organic components, which water
would enhance by takingadvantage of hydrophobic
interactions. Moreover, the aqua complex Et3B·OH2
can more readily undergo the transmetalation.
To our delight, the addition of 10 mol% of a-cyclo- Synthesis of 7a
dextrin (a-CD) improved the yield of 7f to 84% com-
1-Hexene (5a, 379 mg, 4.5 mmol) was added to a solution of
pared to Table 2, entry 6 (Scheme 4). Interestingly, ad-
ditions of b-cyclodextrin (b-CD) and g-cyclodextrin
(g-CD) showed less efficiency.[12] The effect was also
examined in the reaction of benzaldehyde (1a) with
the trialkylborane 6g havinga meta-substituted benzyl
ether moiety. In the absence of a-CD, the reaction
completely failed to afford the desired product. The
addition of 10 mol% of a-CD enabled the conversion
of 1a to the correspondingalcohol 7g albeit the yield
was low.[13] Unfortunately, additions of b-CD or g-CD
could not improve the yield. The exact role of a-CD
is not clear at this stage.[14,15]
borane-dimethyl sulfide (commercially available from Al-
drich, 10M, 0.15 mL, 1.5 mmol) in THF (2 mL) and the so-
lution was stirred for 3 h at 08C. Dimethyl sulfide was then
removed under vacuum (30 torr) at 08C for 1 h to prepare
trihexylborane (6a). At the same time, in a glovebox filled
with argon, Ni
ACHTREUNG
other reaction flask. THF (0.5 mL) and P
AHCTREUNG
hexane solution, 0.096 mL, 0.096 mmol) were added drop-
wise. The solution was stirred for 10 min at 08C. Degassed
water (20 mL) and benzaldehyde (1a, 53 mg, 0.5 mmol)
were then added. Finally, the trihexylborane (6a) prepared
in advance was transferred to the mixture via a syringe
under argon. The resulting mixture was allowed to warm to
room temperature and stirred for 20 h. Extraction with
hexane/ethyl acetate (5:1) followed by concentration afford-
ed the crude product. After the crude product obtained had
been oxidized under the same conditions for the synthesis of
4a, extraction and purification provided 1-phenyl-1-heptanol
(7a); yield: 71 mg(0.37 mmol, 74%).
In conclusion, we have found an example of the al-
kylation of aldehydes in water and the unique effect
of water as a solvent in the reaction. In addition, an
interestingeffect of cyclodextrins was observed.
Experimental Section
Synthesis of 3a
Acknowledgements
In
0.04 mmol) was placed in a reaction flask. THF (0.5 mL)
and P(t-Bu)3 (purchased from Wako and diluted to prepare
a
glovebox filled with argon, Ni(COD)2 (11 mg,
A
This work was supported by Grants-in-Aid for Scientific Re-
search and COE Research from the Ministry of Education,
ACHTREUNG
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www.asc.wiley-vch.de
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Koji Hirano et al.
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Culture, Sports, Science, and Technology, Japan. K.H. ac-
knowledges JSPS for financial support.
[6] The only precedent: C. C. K. Keh, C. Wei, C.-J. Li, J.
Am. Chem. Soc. 2003, 125, 4062–4063.
[7] Recently, Woodward has reported alkylation of alde-
hydes with air-stable trialkylaluminum reagents in or-
ganic solvent under nickel catalysis: K. Biswas, O.
Prieto, P. J. Goldsmith, S. Woodward, Angew. Chem.
Int. Ed. 2005, 44, 2232–2234.
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