Chlorodimethylaluminum-promoted nucleophilic addition of lithium pentamethylcyclopentadienide to aliphatic aldehydes and DDQ-mediated carbon-carbon bond cleavage of the adducts providing the parent aldehydes

Article abstract of DOI:10.1016/j.tetlet.2005.10.159

Treatment of aliphatic aldehyde with lithium pentamethylcyclopentadienide in the presence of chlorodimethylaluminum provided the corresponding carbinol in excellent yield. The carbinol returns to the parent aldehyde and pentamethylcyclopentadiene by the a

Full text of DOI:10.1016/j.tetlet.2005.10.159

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 163–166
Chlorodimethylaluminum-promoted nucleophilic addition of lithium
pentamethylcyclopentadienide to aliphatic aldehydes and
DDQ-mediated carbon–carbon bond cleavage of the
adducts providing the parent aldehydes
Minoru Uemura, Hideki Yorimitsu* and Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto-daigaku Katsura,
Nishikyo-ku, Kyoto 615-8510, Japan
Received 29 September 2005; revised 25 October 2005; accepted 31 October 2005
Available online 16 November 2005
Abstract—Treatment of aliphatic aldehyde with lithium pentamethylcyclopentadienide in the presence of chlorodimethylaluminum
provided the corresponding carbinol in excellent yield. The carbinol returns to the parent aldehyde and pentamethylcyclopentadiene
by the action of a catalytic amount of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ).
Ó 2005 Elsevier Ltd. All rights reserved.
We have been interested in the use of pentamethylcyclo-
pentadiene (Me5C5H, Cp*H) and its anionic form
the lithium enolate of 1a. To overcome the limitation, a
number of additives are examined to attain selective
nucleophilic attack to the carbonyl group of aliphatic
aldehyde. We luckily found that chlorodꢀimethylalumi-
num assists the addition reaction of Cp* to aliphatic
aldehydes, which is disclosed herein.
(Me5C5 , Cp*ꢀ) as reagents in organic synthesis. In
ꢀ
the previous report,1 we demonstrated that Cp*Li adds
to aromatic aldehydes to yield the corresponding alco-
hols2 and that the adducts return to the parent alde-
hydes and Cp*H via carbon–carbon bond cleavage
upon heating or treatment with acid. On the other hand,
several attempted reactions of aliphatic aldehydes with
Cp*Li resulted in failure. For instance, treatment of
dodecanal (1a) with Cp*Li yielded the corresponding
adduct 2a in only 35% yield (Eq. 1). The byproducts
comprised b-hydroxy aldehyde 3 and a,b-unsaturated
aldehyde 4. The formation of the byproducts means that
Cp*Li unfortunately worked as a bulky base to generate
Chlorodimethylaluminum (6.0 mmol) was added to a
n
suspension of Cp*Li (6.0 mmol, generated from BuLi
and Cp*H) in THF at ꢀ20 °C, and the resulting suspen-
sion was stirred for 30 min. Aldehyde 1a (5.0 mmol) was
added, and the mixture was stirred at ꢀ20 °C for 1 h.
After aqueous workup, purification on silica gel yielded
the desired alcohol 2a in 92% yield (Table 1, entry 1,
from 1 to 2). Trace amounts of 3 and 4 were detected
Cp*Li (1.2 equiv)
THF, –20 ˚C, 1 h
O
O
OH
nC10H21
nC10
H
O
then H2O
21 + etc.
nC10H21
nC10H21
+
+
nC10H21
H
H
ð1Þ
Cp*
nC10H21
H
HO
1a
2a
35% yield
3
4
Keywords: Pentamethylcyclopentadiene; Nucleophilic addition; Carbon–carbon bond cleavage; Chlorodimethylaluminum.
*
Corresponding authors. Tel.: +81 75 383 2441; fax: +81 75 383 2438; e-mail addresses: yori@orgrxn.mbox.media.kyoto-u.ac.jp;
oshima@orgrxn.mbox.media.kyoto-u.ac.jp
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.10.159

164
M. Uemura et al. / Tetrahedron Letters 47 (2006) 163–166
Table 1. Nucleophilic addition of Cp*Li to aliphatic aldehydes and
carbon–carbon bond cleavage of the adducts affording the parent
aldehydes and Cp*H
reactions did not go to completion and ca. 20% of 1 was
left. The reaction with keto aldehyde, 11-oxo-2-undec-
anone, exhibited unsatisfactory chemoselectivity (Eq. 2).
Cp*Li (1.2 equiv)
Me2AlCl (1.2 equiv)
THF, –20 ˚C, 1 h
then H2O
Removal of the Cp* group of 2, which results in recov-
ery of 1, can represent a protective method of aliphatic
aldehydes. Contrary to the previous report,1 carbinols
2 were stable under acidic conditions or at high temper-
ature. By extensive screening of reaction conditions, a
strong oxidant, 2,3-dichloro-5,6-dicyanobenzoquinone
(DDQ), proved to effect smooth carbon–carbon bond
cleavage3 to afford the parent aldehyde 1 and Cp*H.
Treatment of 2a with 1 mol % of DDQ in refluxing tolu-
ene for 12 h furnished 1a in 92% isolated yield (entry 1,
from 2 to 1), with concomitant production of quantita-
tive Cp*H. In the presence of DDQ, all the carbinols 2
were transformed into the parent aldehydes (Table 1,
from 2 to 1). Carbinols 2e and 2g having polar cyano
and ester moieties underwent the removal of the Cp*
group more slowly. The sterically hindered cyclohexyl
group of 2c also retarded the reaction. Other organic
oxidants such as chloranil, 2,3-dichlorobenzoquinone,
trityl tetrafluoroborate (Ph3C+BF4ꢀ) also promoted
the removal albeit the efficiency was much lower.
OH
Me
Me
Me
O
R
H
R
Me
DDQ (0.01 equiv)
toluene, reflux
1
2
Me
Entry
R
From 1
to 2 (%)
From 2
to 1a (%)
1
2
3b
4
5
6
7
CH3(CH2)10 (a)
PhCH2CH2 (b)
cyclo-C6H11 (c)
tC4H9 (d)
NC(CH2)5 (e)
Cl(CH2)9 (f)
92
94
97
<10
89
93
92 (12 h)
80 (12 h)
82 (24 h)c
—
75 (24 h)
95 (12 h)
81 (36 h)
CH3OC(@O)(CH2)4 (g)
82
a The reaction time of each run is in parentheses.
b To complete the reaction, 1.5 equiv of Cp*Li and Me2AlCl were
used.
c Isolated as 1-cyclohexylpentanol after treatment of the crude oil with
n-butyllithium.
Cp*Li (1.0 equiv)
OH
O
OH OH
O
O
Me2AlCl (1.0 equiv)
+
ð2Þ
Cp*
Cp*
Cp*
H
8
8
8
THF, –20 ˚C, 1 h
then H2O
41%
18%
in the crude oil. The role of chlorodimethylaluminum is
unclear. Chlorodimethylaluminum can serve as a Lewis
acid, activating the carbonyl group. Alternatively,
Me2Cp*Al reagent would be formed via transmetalation
and can enable the selective nucleophilic attack. Other
Lewis acids such as chlorotrimethylsilane, triethylalumi-
Chlorodimethylaluminum also facilitated the addition
of Cp*Li to dihexyl ketone (5) (Eq. 3). Without the
additive, none of the adduct 6 was obtained. Interest-
ingly, heating 6 in toluene at reflux for 30 h afforded 5
in 98% yield, along with Cp*H. It is worth noting that
DDQ accelerated the transformation (reflux, 12 h).
Cp*Li (2.0 equiv), Me2AlCl (2.0 equiv)
THF, –20 ˚C, 1 h
then H2O, 97%
OH
O
ð3Þ
nC6H13 nC6H13
nC6H13 nC6H13
no additives, refluxing toluene, 30 h, 98%
DDQ (0.01 equiv), refluxing toluene, 12 h, 97%
Cp*
5
6
num, and magnesium dibromide were much less effective
than chlorodimethylaluminum. Titanium tetraisoprop-
oxide comparably promoted the addition (81% yield).
Although the mechanism operating in the DDQ-pro-
moted carbon–carbon bond cleavage is not clear at this
stage, we are tempted to assume two possible mech-
anisms (Scheme 1). One mechanism involves hydride
abstraction by DDQ, a strong hydride acceptor.4
DDQ would abstract the hydride at the 1-methyl group
of the Cp* group,5 which leads to the generation of alde-
hyde 1, tetramethylfulvene (7), and 8. Protonation of 7
with 8 would produce unstable pentamethylcyclopenta-
dienyl cation (Cp*+). The cyclic 4p-electronic cation
Cp*+ would be a hydride acceptor powerful enough to
abstract hydride from 2 to give oxonium cation 9, 7,
and Cp*H. The combination of the oxonium cation 9
A variety of aliphatic aldehydes were subjected to the
nucleophilic addition (Table 1, from 1 to 2). The reac-
tion of cyclohexanecarbaldehyde (1c) provided 2c in
excellent yield. Sterically demanding pivalaldehyde (1d)
resisted the reaction, and 1d remained untouched. The
reaction was highly chemoselective. Cyano, chloro,
and ester moieties did not interfere with the reaction
(entries 5–7). When catalytic amounts (10 mol %, for
instance) of chlorodimethylaluminum were used, the

M. Uemura et al. / Tetrahedron Letters 47 (2006) 163–166
<Hydride abstraction by DDQ>
165
NC
CN
O
O
O
Cl
OH
Me
H
R
1
Me
Me
Cl
OH
Cl
H
Cl
O
R
hydride abstraction
H
R
DDQ
Me
Me
H
Me
HO
CN
8
H
1
2
CN
Me
Me
2Me
5Me
Me
7
3Me
4Me
– RCHO 1
Me
Me
Me
Me
Me
Me
Me
protonation
H
O+
+
+
Me
H
Me
+
Me
Me 7
Me
H
R
Me
Me
Cl
H
O
9
H
1
H
R
2Me
5Me
Me
Me
3Me
4Me
Cl
OH
CN
+
+
Me
Me
– O
Me
CN
single
electron
transfer
<Single electron transfer>
Cl
Cl
Cl
O
O–
Cl
OH
OH
Me
Me
Me
O
CN
•
CN
•
R
12
DDQ
10
CN
Me
CN
Me
O•+
H
single
electron
transfer
O
Me
2
Me
Me
Me
Me
Me
R
R
Me
11
•
1
Me
Me
Me
Scheme 1.
and fulvene 7 again generates Cp*+ to complete the cat-
alytic cycle. Alternatively, a mechanism involving single
electron transfer is probable.6 Single electron transfer
from 2 to DDQ generates radical anion 10 and radical
cation 11. The latter undergoes fragmentation into pen-
tamethylcyclopentadienyl radical (Cp*Å) and 1. Cp*Å
would be oxidized by 12 into Cp*+. The cation Cp*+
participates in the same catalytic cycle in the hydride
abstraction mechanism. Noteworthy is the fact that no
deuterium incorporation was observed in the cleavage
reaction in deuterated toluene, which eliminates the
possibility of hydrogen abstraction of the intermediary
radicals from solvent.
group of 2c. Namely, rate-determining hydride abstrac-
tion or single electron transfer would be retarded. It is
worth noting that the silyl ether of 2b completely re-
sisted the cleavage upon treatment with DDQ in boiling
toluene.
In summary, we found that chlorodimethylaluminum
facilitates nucleophilic addition of lithium pentamethyl-
cyclopentadienide to aliphatic aldehydes. The adducts
return to their parent aldehydes by the DDQ-mediated
cleavage of the Cp*–CR(H)OH bond. Metal-mediated
carbon–carbon bond cleavage is a transformation that
is attracting increasing attention.3 The DDQ-mediated
cleavage provides a new protocol for carbon–carbon
bond cleavage without metal reagents.
The hydroxy group of 2 plays a key role in the carbon–
carbon bond cleavage process. Additional polar groups
such as cyano and ester groups in 2e and 2g would
prevent the weak interaction between the hydroxy
group and electron deficient species such as DDQ and
Cp*+. The bulkier cyclohexyl group of 2c hampered
the access of the electron deficient species to the hydroxy
Acknowledgements
This work was supported by Grants-in-Aid for Scientific
Research, Young Scientists, and COE Research, from

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M. Uemura et al. / Tetrahedron Letters 47 (2006) 163–166
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the Ministry of Education, Culture, Sports, Science, and
Technology, Government of Japan.
Supplementary data
Supplementary data including experimental details and
characterization data for new compounds can be found
online. Supplementary data associated with this article
can be found, in the online version, at doi:10.1016/
j.tetlet.2005.10.159.
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