Ruthenium catalysts for controlled mono- and bis-allylation of active methylene compounds with aliphatic allylic substrates

Article abstract of DOI:10.1002/adsc.200900498

The allylation of 1,3-dicarbonyl compounds and malononitrile with aliphatic allylic substrates is achieved under mild conditions in the presence of new ruthenium catalysts. The ruthenium complex [Ru(C₅Me₅) (2-quinolinecarboxylato)(CH

Full text of DOI:10.1002/adsc.200900498

UPDATES
DOI: 10.1002/adsc.200900498
Ruthenium Catalysts for Controlled Mono- and Bis-Allylation of
Active Methylene Compounds with Aliphatic Allylic Substrates
Hui-Jun Zhang,a,b Bernard Demerseman,b Zhenfeng Xi,a,*
and Christian Bruneaub,*
a
Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular
Engineering of Ministry of Education, College of Chemistry, Peking University, Beijing 100871, Peopleꢀs Republic of
China
Fax : (+86)-10-6275-1708; e-mail: zfxi@pku.edu.cn
Sciences Chimiques de Rennes, UMR 6226 CNRS-Universitꢁ de Rennes 1, Catalyse et Organomꢁtalliques, Universitꢁ de
b
Rennes 1, 35042 Rennes Cedex, France
Fax : (+33)-2-2323-6939; e-mail: christian.bruneau@univ-rennes1.fr
Received: July 16, 2009; Published online: October 22, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900498.
Abstract: The allylation of 1,3-dicarbonyl com-
pounds and malononitrile with aliphatic allylic sub-
strates is achieved under mild conditions in the
presence of new ruthenium catalysts. The rutheni-
ty of this transformation. However, 1,6-dienes are val-
uable building blocks and their cycloisomerization
with various organometallic catalysts has been exten-
sively studied.[4] The double allylation of 1,3-dicarbon-
yl compounds has been achieved using the rutheni-
um complex [Ru
ACHTUNGTRENNUNG
to)(CH2CHCH-n-Pr)]
the synthesis of mono-allylated branched deriva-
tives. On the other hand, the parent complex
G
um(0) complex RuACTHUNGRTENNU(G cod)CATHUNGTRENUN(NG cot) (cod=1,5-cycloocta-
diene, cot=1,3,5-cyclooctatriene) as precatalyst.[5] The
bis-allylation reaction was achieved at 808C using N-
methylpiperidine as solvent, and a similar procedure
was recently used for the first step in a “one-pot”
double allylation/cycloisomerization of 1,3-dicarbonyl
[Ru
G
N
[PF6]
as
a
precatalyst,
straightforwardly favours the bis-allylation of the
procarbonucleophiles leading to bis-allylated bis-
linear products. The involvement of the two preca-
talysts provides a sequential synthesis of unsymmet-
rical mixed linear-branched bis-allylated derivatives.
compounds using the RuClACTHNUTRGENN(UG Cp*)AHCTUNGTERNN(UGN cod) precatalyst
(Cp*=pentamethylcyclopentadienyl).[6]
We report herein a sequential access to novel un-
symmetrical bis-allylated linear-branched derivatives
from active methylene compounds and aliphatic allyl-
ic substrates, using the ruthenium complexes
À
Keywords: allylation; C C bond formation; homo-
geneous catalysis; regioselectivity; ruthenium
[Ru
Pr)]
(Cp*)(2-quinolinecarboxylato)(h3-CH2CHCH-n-
ACHTUNGTRENNUNG
AHCTNUGETRG[NUNN BF4] and [RuACHUTGNTERNNUG(Cp*)AHCTUNGERTN(GNUN MeCN)3]CATHNUGTREN[NGUN PF6] as precata-
lysts. The former allowed the regioselective formation
of mono-allylated branched derivatives whereas the
latter provided an access to bis-allylated bis-linear de-
rivatives under very mild conditions.
Introduction
Ruthenium complexes have recently attracted an in-
creasing interest as catalysts in allylic substitution re-
actions,[1] a versatile tool to form carbon-carbon and Results and Discussion
heteroatom-carbon bonds.[2] Furthermore, the reac-
tion of malonate-type anions with allylic substrates Since the [Ru(Cp)(2-quinolinecarboxylato)ACTHNUTRGNEUNG
(h3-allyl)]
has been largely employed as a useful test for the dis-
covery of new catalysts and the investigation of their for nucleophilic allylic substitution with O-nucleo-
catalytic properties.[3] By contrast, little attention has philes,[7] (h3-al-
[Ru(Cp*)(2-quinolinecarboxylato)
ACHTUNGTREN[NUNG PF6] complex has disclosed efficiency as precatalyst
A
ACHTUNGTRENNUNG
been paid to the formation of 1,6-dienes through lyl)][PF6 or BF4] ruthenium(IV) precatalysts have al-
ruthenium-catalyzed double allylation of active meth- lowed highly regioselective nucleophilic substitution
ylene compounds, and especially to the regioselectivi- of aliphatic allylic substrates in favour of branched
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Adv. Synth. Catal. 2009, 351, 2724 – 2728

Ruthenium Catalysts for Controlled Mono- and Bis-Allylation
products,[8] and recently provided a novel access to
UPDATES
Whereas the second allylation of the mono-allylat-
functionalized vinylsilanes.[9] To extend the scope of ed derivatives 1a and 1b was negligible in the pres-
ruthenium-catalyzed allylation reactions using cata- ence of the catalyst precursor I, it was made success-
lysts based on a (Cp*)Ru fragment, the allylation of ful using hex-2-en-1-yl ethyl carbonate as allylic sub-
2,4-pentanedione and malononitrile with hexenyl strate in the presence of the ruthenium complex [Ru-
chloride was investigated. Hexenyl chloride was in-
ACHTUGNTRENNN(GU Cp*)ACHTUNGERTNNG(NU MeCN)3]ACHTGERUNTNNG[U PF6] as a distinct precatalyst II
volved as a 4:1 mixture of linear n-PrCH=CHCH2Cl (Scheme 2).
and branched n-PrCH(Cl)CH=CH2 isomers resulting
from the reaction between PCl3 and 2-(E)-hexen-1-
ol.[10] Using the ruthenium complex [Ru
ACHTUNGTRENNUNG
nolinecarboxylato)(h3-CH2CHCH-n-Pr)]
ACHTUNGTRENNUNG
precatalyst in the presence of potassium carbonate as
a base, the reaction occurred at room temperature.
Starting from equimolar mixtures of hexenyl chloride,
procarbonucleophile, and potassium carbonate in ace-
tonitrile as solvent, complete conversion of the pro-
carbonucleophile was reached in the presence of
3 mol% of I at room temperature (Scheme 1).
Starting from 2,4-pentanedione and malononitrile,
the mono-allylated branched derivatives 1a and 1b
were formed with an excellent selectivity (>95%) as
monitored by GC analysis. Bis-linear and mixed
linear-branched bis-allylated derivatives (vide infra)
appeared as minor products. The pure mono-allylated
branched derivatives 1a and 1b were obtained after
chromatographic work-up as colourless oils in 82%
and 53% yields, respectively. These selectivities are in
line with our previous results obtained from the reac-
tion of dimethyl malonate with hex-2-en-1-yl carbon-
ate, and thus confirm the high regioselectivity in
favour of the branched isomers using catalysts based
Scheme 2. Synthesis of unsymmetrical linear-branched bis-
allylated products 2a–c. Experimental conditions: 1a or b:
0.5 mmol, allylic carbonate: 0.5 mmol, K2CO3: 0.5 mmol,
catalyst II: 3 mol%, acetonitrile (4.0 mL) as solvent, 408C,
2 days.
on
a
Ru
(Cp*)(2-quinolinecarboxylato) fragment,
This second allylation step was, however, more dif-
ficult as compared to the first one. The presence of a
mineral base (K2CO3) to stimulate the formation of
the anionic carbonucleophile species was required al-
though a carbonate was used as allylic substrate. Fur-
thermore, a longer reaction time of 2 days and a
slight thermal activation (408C) were also needed to
reach completion of the reaction. The unsymmetrical
linear-branched bis-allylated products 2a and 2c were
formed with excellent regio- and stereoselectivities
and subsequently isolated as colourless oils in 89%
and 87% yields, respectively. The bis-allylated product
2b bearing distinct n-propyl and methyl groups in the
branched and linear chains, respectively, was similarly
prepared starting from 1a and crotyl ethyl carbonate.
Starting directly from the initial procarbonucleo-
phile, precatalyst II allowed the straightforward bis-
allylation of active methylene compounds even at
room temperature. In this case, however, the reaction
led to the major formation of bis-linear products. In
contrast, some experiments using cinnamyl instead of
hexenyl allylic substrates showed a highly favoured
formation of mono-allylated branched derivatives as
might be expected from previous studies using preca-
talyst II.[3a] Typically, the reaction of 2.2 equivalents of
hexenyl chloride with 2,4-pentadione, dimethyl malo-
starting from aliphatic allylic substrates.[8]
Scheme 1. Synthesis of mono-allylated branched products 1a
and b. Experimental conditions: pronucleophile: 0.5 mmol,
hexenyl chloride: 0.5 mmol, base: 0.5 mmol, catalyst I:
3 mol%, acetonitrile (4.0 mL) as solvent, room temperature,
16–18 h.
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Hui-Jun Zhang et al.
UPDATES
nate, or malononitrile, resulted in the consumption of
Of interest, the formation of bis-allylated bis-
these procarbonucleophiles and the formation of sym- branched products was not detected. This observation
metrical bis-allylated bis-linear (LL) derivatives as suggested that the presence of a branched chain in
major products (Scheme 3). The conversion into the mono-allylated intermediates forced the second ally-
(LL) bis-allylated bis-linear products was close to lation towards the formation of the linear allylic frag-
85% as indicated by GC analysis, independently of ment. This might account for the highly regioselective
the nature of the procarbonucleophile. Moreover, formation of unsymmetrical linear-branched bis-ally-
very similar results were obtained using hex-2-en-1-yl lated products 2a–c starting from mono-allylated
ethyl carbonate instead of hexenyl chloride as allylic branched derivatives 1a and 1b in the presence of pre-
substrate. The bis-allylation of 2,4-pentadione or ma- catalyst II.
lononitrile was achieved using K2CO3 as a base. Start-
The conversion of active methylene compounds
ing from dimethyl malonate, completion of the reac- into bis-allylated bis-linear (LL) derivatives obviously
tion was reached using Cs2CO3 as a base. We found involved a transient formation of the corresponding
that the ruthenium complex RuACTHNUTRGENNUG(acac)2ACHTUNGTERN(NUGN MeCN)2 mono-allylated linear products. These intermediates
(acac=acetylacetonato) III,[11] which contains no cy- were more easily detected starting from an equimolar
clopentadienyl ligand was also efficient for the bis-al- pronucleophile/allylic substrate ratio. However, their
lylation of malononitrile with hexenyl chloride in the formation remained not selective enough to subse-
presence of K2CO3, and led to the favoured formation quently attempt separation from the simultaneously
of bis-linear product 3c with the same activity as com- formed bis-allylated products and unreacted procar-
plex II. The concomitent minor formation (around bonucleophile substrates. The synthesis of mono-ally-
15%) of bis-allylated (LB) and mono-allylated (B) lated derivatives was nevertheless possible using a
derivatives in a variable ratio depending on the pro- large excess of procarbonucleophile. Thus, using cata-
carbonucleophile was observed, but it was possible to lyst III and starting from malononitrile and hexenyl
separate and isolate the pure bis-allylated bis-linear chloride in a 3:1 molar ratio, the reaction mainly af-
(LL) products 3a–c as colourless oils in 70–72% forded the mono-allylated 2-[(E)-hex-2-en-1-yl]malo-
yields by chromatography on silica gel.
nonitrile derivative that was separated from minor
products and unreacted malononitrile by chromatog-
raphy and isolated as a colourless oil in 71% yield,
relative to the allylic substrate.
Allyl chloride and allyl ethyl carbonate were in-
volved as unsubstituted allylic substrates leading to
only one type of allylated products with no possible
regioisomers. The bis-allylation of dimethyl malonate
and malononitrile with these simple allylic substrates
was achieved using precatalyst II to afford dimethyl
diallylmalonate 4a, and diallylmalononitrile 4b, re-
spectively (Scheme 4). The complete conversion of di-
methyl malonate or malononitrile into 4a and 4b, re-
Scheme 3. Synthesis of symmetrical bis-allylic bis-linear de-
rivatives 3a–c. Experimental conditions: pronucleophile:
0.5 mmol, hex-2-en-1-yl ethyl carbonate or hexenyl chloride:
1.1 mmol, base: 1.1 mmol, catalyst: 3 mol%, acetonitrile
(4.0 mL) as solvent, room temperature, 16–18 h.
Scheme 4. Synthesis of bis-allyl derivatives 4a and b. Experi-
mental conditions: pronucleophile: 0.5 mmol, allyl ethyl car-
bonate: 1.1 mmol or allyl chloride: 1.5 mmol, base:
1.1 mmol, catalyst II: 3 mol%, acetonitrile (4.0 mL) as sol-
vent, room temperature, 16–18 h.
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Ruthenium Catalysts for Controlled Mono- and Bis-Allylation
UPDATES
allylic substrate and base in acetonitrile (amounts, reaction
time and temperature as indicated in captions of the
Schemes). After completion of the reaction, the slurry was
filtered through a plug of silica gel and the filtrate was con-
centrated under reduced pressure. The resulting crude oil
was purified by column chromatography using silica gel and
petroleum ether/diethyl ether (10:1–20:1) as eluent.
spectively, was reached at room temperature using
Cs2CO3 as a base, indistinctly starting from a slight
excess of allyl chloride or allyl ethyl carbonate. The
unsubstituted allyl substrate offers no steric hindrance
and high yields in bis-allylated isolated products (91–
92%) were obtained. Note also that no reaction was
detected in the absence of appropriate ruthenium pre-
catalyst.
Characterization of Compounds
HR-MS determinations and characteristic NMR spectra and
spectroscopic data are given in the Supporting Information.
Conclusions
The examples developed in this study highlight a new
catalytic route to achieve the bis-allylation of active
methylene compounds such as 1,3-dicarbonyl com-
pounds and malononitrile. Mainly based on pentame-
thylcyclopentadienyl-ruthenium catalysts, allylation
reactions occurred under very mild conditions in the
Acknowledgements
H.J.Z. is grateful to the Ambassade de France in China and
to the International Program of the Natural Science Founda-
tion of China for a Ph. D. financial support.
presence of innocuous bases. A [Ru
ACHTUNGTREN(NUGN Cp*)(2-quinoli-
necarboxylato)(CH2CHCH-n-Pr)][BF4] precatalyst al-
lowed the regioselective synthesis of mono-allylated
branched products starting from unsymmetrical ali-
AHCTUNGTRENNUNG
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ACHTUNGTRNE(NUNG Cp*)-
A
ACHTUNGTRENNUNG
ed derivatives but with preferential formation of
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Experimental Section
General Considerations
The reactions were carried out under an inert atmosphere of
argon according to Schlenk techniques. HPLC grade aceto-
1
nitrile was used as purchased. H and 13C NMR spectra were
recorded at 297 K on a Bruker DPX 200 instrument and ref-
erenced internally to the solvent peak. HR-MS were record-
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TOF with ESI source mass spectrometers at the “Centre
Rꢁgional de Mesures Physiques de l’Ouest” (Rennes). The
[Ru
[BF4][8] and [Ru
prepared as reported previously.
ACHTUNGTRENNUNG
(Cp*)(2-quinolinecarboxylato)(h3-CH2CHCH-n-Pr)]
A
[PF6][12] precatalysts were
ACHTUNGTRENNUNG(Cp*)ACHTUNGTREG(NNUN MeCN)3]ACHTNUGTRENNUGN
General Procedure for the Synthesis of Allylated
Compounds
As a general procedure for catalytic experiments, the pronu-
cleophile and the catalyst were added to a stirred mixture of
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