Revisit to the reduction of allylic chlorides to less substituted olefins by a low-valent chromium species in the presence of a proton source

Article abstract of DOI:10.1016/S0040-4039(00)02140-7

Allylic chlorides have been reduced to afford less substituted olefins by a low-valent chromium species in the presence of an alcoholic proton source. This process certainly has synthetic benefits since the regio-selectivity of the reduction is high and the reaction conditions are mild and nearly neutral.

Full text of DOI:10.1016/S0040-4039(00)02140-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 939–941
Revisit to the reduction of allylic chlorides to less substituted
olefins by a low-valent chromium species in the presence of a
proton source
Mineko Omoto,a Nobuo Kato,b,* Tetsuya Sogonb and Akira Morib
aInterdisciplinary Graduate School of Engineering Sciences, Kyushu University, Kasuga, Fukuoka 816-8580, Japan
bInstitute of Advanced Material Study, Kyushu University, Kasuga, Fukuoka 816-8580, Japan
Received 1 November 2000; revised 15 November 2000; accepted 17 November 2000
Abstract—Allylic chlorides have been reduced to afford less substituted olefins by a low-valent chromium species in the presence
of an alcoholic proton source. This process certainly has synthetic benefits since the regio-selectivity of the reduction is high and
the reaction conditions are mild and nearly neutral. © 2001 Elsevier Science Ltd. All rights reserved.
In 1977, a procedure for the in situ preparation of a
low-valent chromium species (Cr(II)) in an aprotic
medium was reported by Hiyama et al.1 Since then,
Cr(II) has been widely used in organic synthesis espe-
cially in the CꢀC bond formation reactions of allylic
(Nozaki–Hiyama reaction) or vinylic halides (Nozaki–
Hiyama–Kishi reaction) with aldehydes.2
state (Scheme 1). Furthermore, the reaction proceeds
under nearly neutral conditions. Despite the advanta-
geous aspects of this synthetic procedure, applications
have been limited in comparison with other more com-
mon methods, such as the acid hydrolysis of
allylstanannes6 or allyltosylhydrazides7 and the hydride
reduction of allyltriphenylphosphonium halides.8 Here,
we revisit the double bond migrative reduction of allylic
halides by the Cr(II) species to report the synthetic
utility.
Prior to these studies, Cr(II) was generated in an
aqueous medium and utilized mainly for the reductive
cleavage of the carbonꢀhalogen bond.3 Among these
earlier investigations, the reduction of allylic halides is
noteworthy. Castro et al. reported that both cis- and
trans-crotyl chloride are reduced by chromous sulfate
in an aqueous DMF to afford 1-butene in high selectiv-
ity.4 This result suggests that the protonation of the
allylchromium species must be faster than the radical
homo-coupling reaction, affording dimeric products as
are obtained in the absence of a proton source.5 And
more importantly from the synthetic aspect, similarly to
CꢀC bond formation with aldehydes, protonation
occurs at the g-position of the allylchromium species to
give a less substituted olefin, i.e. a thermodynamically
less stable olefin, through the six-membered transition
At first, we re-checked the regio-selectivity of this reac-
tion with the use of geranyl chloride (1a) as a substrate.
The allylchromium species was generated by Hiyama’s
conditions.1 Similar to the originally reported results in
an aqueous medium,4 the reduction proceeds quantita-
tively even in the presence of a limited amount of an
alcoholic proton source in an aprotic solvent system, a
mixture of THF and DMF. However, a mixture of
dimeric products arising from the radical homo-coup-
ling reaction5 was obtained when bulky t-BuOH was
used as a proton source. The regio-selectivity of the
reduction is high enough as shown in Table 1 to give
3,7-dimethylocta-1,6-diene (2a) exclusively.
Cr(II)SO4
O
H
Cl
H
CrLn
aq. DMF
Scheme 1. Double bond migrative reduction of crotyl chlorides by Cr(II)SO4 in an aqueous medium.4
Keywords: Hiyama reactions; olefins; protonation; reduction; regioselection.
* Corresponding author. Tel.: +81-92-583-7809; fax: +81-92-583-7810; e-mail: kato-n@cm.kyushu-u.ac.jp
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02140-7

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M. Omoto et al. / Tetrahedron Letters 42 (2001) 939–941
CrCl3 – LiAlH4
Cl
ROH, THF–DMF
1a
1b
2a
2b
3a
3b
CrCl3 – LiAlH4
Cl
ROH, THF–DMF
Scheme 2. Double bond migrative reduction of allylic chlorides by Cr(II) species in the presence of alcoholic proton sources.
Table 1. The regio-selectivity of the Cr(II)ꢀROH reduction
of geranyl chloride (1a) and cinnamyl chloride (1b)a
The authors then focused their attention on the stereo-
selectivity. If this reduction actually involves the six-
membered transition state as shown in Scheme 1, then
the stereo-structure of the substrate should direct a
diastereoselective protonation. In fact, the protonation
of the allylchromium species generated from (3R,8S)-7-
chloro-1-iridene derivative (1d)11 occurs on the less
hindered face to afford (1R,3R,8S)-irid-2(7)-ene deriva-
tive (2d)‡ predominantly. The stereochemistry of the
newly formed stereogenic center was confirmed by an
NOE experiment indicated in Scheme 4 and a further
conversion of 2d into all-cis-iridodiol (4)12 through
hydroboration on the exocyclic olefin.
Substrate
Proton source
Ratio of 2:3
Geranyl chloride (1a)
H2O
MeOH
EtOH
i-PrOH
t-BuOH
>99.5:<0.5
>99.5:<0.5
>99.5:<0.5
98.5:1.5
1a
1a
1a
1a
85:15b
Cinnamyl chloride (1b)
1b
EtOH
i-PrOH
95.5:4.5
97.5:2.5
a Cr(II) was generated from 5 mmol of CrCl3 and 2.5 mmol of
LiAlH4 in THF (5 ml) and the resultant was diluted with 10 ml of
DMF. Into the resulted suspension were added 10 mmol of the
indicated protone source and a DMF (5 ml) solution of 2 mmol of
the substrate and 2 mmol of decane as a analytical standard. After
stirring under an inert atmosphere for 15–24 h at room temperature,
the reaction mixture was extracted with hexane and the organic
phase was directly analyzed by GC-MS. The combined chemical
yield of the reductates is quantitaive within an experimental error
except the case when t-BuOH was used as a proton source.
It has been known that the same crotylchromium spe-
cies is generated from both crotyl chloride (1-chloro-2-
butene) and 3-chloro-1-butene in order to locate the
metal at the less crowded circumstances of the allylic
system.1 Taking this feature into account, it is possible
to isomerize a thermodynamically more stable olefin to
a less stable one by a sequence of allylic chlorination
and Cr(II)ꢀROH reduction. Scheme 5 shows an exam-
ple of this type of transformation. The allylic chlorina-
tion of the internal olefin of 5 was achieved by the
hypochlorous acid treatment,13 and then the
Cr(II)ꢀROH reduction of the resulting chloride fur-
nished the isomerization of the double bond to give 6 in
good yield.14
b The combined chemical yield of 2a and 3a is estimated to be ꢀ20%
based on the isolated yield (77%) of non-volatile dimeric products.
The regio-selectivity is maintained in the conjugated
system. As shown also in Table 1, cinnamyl chloride
(1b) was converted into allylbenzene (2b) predomi-
nantly even though the reaction involves a thermody-
namically unfavorable deconjugation process (Scheme
2).
As realized in this example, the aldehyde-selective
nature of the allylchromium species as a nucleophile
allows application of this process to substrates carrying
functional groups other than aldehydic moieties. Thus,
this procedure is certainly an alternative synthetic
method to advantageously obtain less substituted
olefins from allylic halides.
Taking advantage of the nearly neutral conditions, the
synthetic utility of this procedure is emphasized in the
formation of acid-labile compounds, which are difficult
to obtain by alternative methods involving acid hydroly-
sis. For example, the Cr(II)ꢀROH (i-PrOH was used)
reduction of 2-chloromethylbenzo[b]furan (1c)9 success-
fully afforded 2,3-dihydro-2-methylenebenzo[b]furan
(2c),10 which is extremely labile toward both acidic and
basic conditions, in moderate yield together with the
regio-isomer 3c after chromatographic purification
(Scheme 3).†
‡ A colorless oil; [a]2D2 +60.8 (c 1.86, CHCl3); lH (C6D6) 0.99 (3H, d,
J=7.1 Hz; H-6), 1.11 (1H, dm, J=13.0 Hz; H-5), 1.12 (3H, d,
J=7.1 Hz; H-10), 1.45 (1H, dm, J=12.5 Hz; H-4), 1.52 (1H, dm,
J=12.5 Hz; H-4), 1.60 (1H, dm, J=13.0 Hz; H-5), 2.05 (1H, m;
H-8), 2.40 (1H, m; H-1), 2.46 (1H, m; H-3), 3.17 (1H, dd, J=8.8,
8.1 Hz; H-9), 3.42 (1H, dd, J=8.8, 4.6 Hz; H-9), 4.29 (1H, d,
J=12.2 Hz; benzyl), 4.33 (1H, d, J=12.2 Hz; benzyl), 4.93 (1H, m;
H-7), 4.96 (1H, m; H-7), 7.08 (1H, t-like, J=ꢀ8 Hz; Ph-para), 7.17
(2H, t-like, J=ꢀ8 Hz; Ph-meta), and 7.29 (2H, d-like, J=ꢀ8 Hz;
Ph-ortho); lC (C6D6) 17.11 (C-10), 20.08 (C-6), 26.96 (C-4), 33.18
(C-5), 36.47 (C-8), 39.51 (C-1), 47.69 (C-3), 73.11 (benzyl), 73.30
(C-9), 105.19 (C-7), 127.49 (Ph-para), 127.62 (2C, Ph-ortho), 128.46
(2C, Ph-meta), 139.52 (Ph-ipso), and 159.49 (C-2).
† Since it has been known that 2c isomerizes into 3c during a
chromatographic (SiO2) purification,10 the ratio of the isolated
reductates does not directly reflect the regio-selectivity of the reduc-
tion process. 1H NMR of the crude product showed the predomi-
nant formation of 2c.

M. Omoto et al. / Tetrahedron Letters 42 (2001) 939–941
941
CrCl3 – LiAlH4
O
O
O
Cl
i-PrOH, THF–DMF
1c
2c
3c
16%
79%
Scheme 3. Double bond migrative reduction of 1c to 2c.
H
6
NOE
H
1) thexylborane, then H2O2, –OH
CrCl3 – LiAlH4
1
2
3
Cl
H
H
OH
H
7
i-PrOH, THF–DMF
92%
8
H
2) H2, Pd(OH)2/C, EtOH
90% in 2 steps
OBn
OBn
H
H
OH
H
9
1d
2d
4
Scheme 4. Double bond migrative reduction of 1d to 2d and a further conversion into all-cis-iridodiol (4).
OR
OR
OR
OMOM
OMOM
OMOM
RO
RO
RO
CrCl3 – LiAlH4
Ca(OCl)2, KHSO4
i-PrOH, THF – DMF
CH2Cl2 – H2O
R = COCMe3
Cl
81% in 2 steps
5
6
Scheme 5. Transformation of a more substituted internal double bond to a less substituted external double bond.
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