Ruthenium-catalyzed allylation-cyclization reactions of cyclic 1,3-dicarbonyl compounds with 1-vinyl propargyl alcohols

Article abstract of DOI:10.1002/chem.201202414

Ruthenium-catalyzed allylation-cyclization reactions of cyclic 1,3-dicarbonyl compounds with 1-vinyl propargyl alcohols that lead to diverse carbo- or heterocyclic products in a one-pot cascade process are reported. These mechanistically distinct reactions are catalyzed by a single ruthenium(0) complex that contains a redox-coupled dienone ligand. The reaction pathway strongly depends on the substrate substitution pattern, which determines the mode of activation of the 1-vinyl propargyl alcohol. The environmentally benign process, which generates water as the only waste product, is of wide scope and allows the atom-economic synthesis of highly functionalized furans, pyrans, and spirocarbocycles. Ring-producing expert: Ru complexes of redox-coupled cyclopentadienone ligands catalyze various allylation-cyclization reactions of cyclic 1,3-dicarbonyl compounds with 1-vinyl propargyl alcohols through strikingly distinct modes of activation to afford highly functionalized furans, pyrans, and spirocarbocycles (see scheme). Copyright

Full text of DOI:10.1002/chem.201202414

DOI: 10.1002/chem.201202414
Ruthenium-Catalyzed Allylation–Cyclization Reactions of Cyclic
1,3-Dicarbonyl Compounds with 1-Vinyl Propargyl Alcohols
Anita Jonek, Stefanie Berger, and Edgar Haak*[a]
Abstract: Ruthenium-catalyzed allyla-
complex that contains a redox-coupled
dienone ligand. The reaction pathway
strongly depends on the substrate sub-
stitution pattern, which determines the
tion–cyclization reactions of cyclic 1,3-
dicarbonyl compounds with 1-vinyl
propargyl alcohols that lead to diverse
carbo- or heterocyclic products in a
one-pot cascade process are reported.
These mechanistically distinct reactions
are catalyzed by a single ruthenium(0)
mode of activation of the 1-vinyl prop-
argyl alcohol. The environmentally
benign process, which generates water
as the only waste product, is of wide
scope and allows the atom-economic
synthesis of highly functionalized
furans, pyrans, and spirocarbocycles.
Keywords: atom economy · cooper-
ative effects · cyclization · homoge-
neous catalysis · ruthenium
Introduction
Atom-economic transformations of readily and widely ac-
cessible educts to yield products of higher complexity are
particularly important.[1] Especially, ruthenium-catalyzed re-
actions offer a broad range of selective processes for the
conversion of various unsaturated compounds.[2] Nucleophil-
ic additions to vinylidene or allenylidene complexes and
redox isomerizations of allyl and propargyl alcohols have
Scheme 1. Coordination of the chelating substrate with complexes of type
1.
been described in particular, in addition to metathesis and
[3]
À
C C coupling reactions. In previous studies, we have
proceed through strikingly different reaction pathways,
which are determined by the nature of substrate 2. The
transformation of substrates 2 that contain secondary alco-
hol and terminal alkyne moieties (terminal secondary sub-
strates) lead to spirocyclohexanones 4, whereas secondary
alcohol substrates that posses an internal alkyne (internal
secondary substrates) generate dihydropyrans 5 as the major
products. Tertiary alcohol substrates that contain a terminal
alkyne moiety (terminal tertiary substrates) form spirocyclo-
pentenes 6 under the same reaction conditions, whereas the
presence of an internal alkyne and a tertiary alcohol in 2
shown that ruthenium complexes of redox-active cyclopen-
tadienone ligands (1) catalyze various transformations of
propargyl alcohols with a broad range of nucleophiles.[4] Sec-
ondary alcohol substrates can be converted by redox isomer-
ization prior to nucleophilic addition.[4a,d–e,5] Terminal prop-
argyl alcohols allow the formation of various addition prod-
ucts via vinylidene or allenylidene intermediates.[4a–d] 1-Vinyl
propargyl alcohols (2), easily accessible from enones, can be
transformed to yield heterocyclic compounds in an allyla-
tion–cyclization sequence.[4a] Coordination of the chelating
substrate involves the basic coordination site of the electron-
ically coupled ligand, which is crucial for these regioselec-
tive transformations (Scheme 1). Substrates without suitable
hydrogen-bond donors are usually not converted.
(internal tertiary substrates) lead to dihydrofuranes
(Scheme 2).
7
Herein, we report several mechanistically distinct allyla-
tion–cyclization reactions of 2 with cyclic 1,3-dicarbonyl
compounds 3, catalyzed by complexes 1a or 1b. The envi-
ronmentally benign and atom-economic transformations
[a] A. Jonek, S. Berger, Prof. Dr. E. Haak
Institut fꢀr Chemie
Otto-von-Guericke-Universitꢁt Magdeburg
Universitꢁtsplatz 2
39106 Magdeburg (Germany)
E-mail: edgar.haak@ovgu.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201202414.
Scheme 2. Ruthenium-catalyzed transformations of 1-vinyl propargyl al-
cohols 2 with cyclic 1,3-dicarbonyl compounds 3.
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FULL PAPER
Results and Discussion
Catalysts of type 1 catalyze various reactions of unsaturated
alcohols, for example, redox isomerization processes, nucleo-
philic addition, and cyclization reactions.[4] In previous stud-
ies, we found that cyclic 1,3-dicarbonyl compounds add to
propargyl alcohols in the presence of catalyst 1a or 1b to
form dihydropyran compounds (Scheme 3a).[4b] In exten-
Scheme 5. Ruthenium-catalyzed transformation of terminal secondary
substrates.
Table 1. Conversion of terminal secondary substrates 2.
Entry
2
R
Products obtained (yield [%]) with nucleophile 3
Scheme 3. Previously reported conversions of propargyl alcohols with dif-
ferent nucleophiles catalyzed by 1a (selected examples, TFA=trifluoro-
acetic acid).
3a
3b
3c
1
2
3
2a
H
n.c.[a]
n.c.
n.c.
2b Me n.c.
2c
n.c.
4cb (91)
n.c.
Ph
4ca (37)
5ca (39)
6ca (12)
4ca (54)
5ca (21)
6ca (5)
5ca (67)
6ca (19)
n.c.
6cc (5, d.r.[b] =5:3)
7cc (38, d.r.=2:1)
8cc (30)
sion, we were interested if 1-vinyl propargyl alcohols, which
can be regarded as allylic or propargylic systems, would
behave differently. Systems that possess a secondary alcohol
may undergo redox isomerization followed by nucleophilic
addition. 1-Vinyl tertiary propargyl alcohols could allylate
the nucleophile first, followed by a cyclization step. We pre-
viously reported that both types of reactions occur in pres-
ence of pyrrole as the nucleophilic component (Scheme 3b
and c).[4a] The formation of these different products led us
to systematically investigate the reactions of various 1-vinyl-
propargyl alcohols 2 with cyclic 1,3-dicarbonyl compounds 3
catalyzed by complexes of type 1.
4[c]
2c
Ph
4cb (15)
8cc (48)
5[d]
6[f]
2c
2c
Ph
Ph
5cb (16)
n.p.[e]
n.p.
n.c.
[a] n.c.=No conversion. [b] d.r.=Diastereomeric ratio. [c] Reaction per-
formed without TFA. [d] Reaction performed with Ru catalyst 1b.
[e] n.p.=Not performed. [f] Reaction performed without Ru catalyst.
With 1,3-cyclopentanedione (3a) the products 5ca and 6ca
are formed in addition to 4ca (Table 1, entry 3), and they
were formed as the only products when catalyst 1b was used
(Table 1, entry 5). When 4-hydroxycoumarin (3c) was used
the redox isomerization product 8cc was accompanied by
compounds 6cc and 7cc, formed with low diastereoselectivi-
ty in favor of the sterically less-demanding isomers (Table 1,
entry 3). The absence of the acidic additive causes signifi-
cantly slower conversion of nucleophile 3b but encourages
less byproduct formation for reactions with nucleophiles 3a
and 3c (Table 1, entry 4). Pent-1-en-4-yn-3-ol (2a) and hex-
4-en-1-yn-3-ol (2b) contain a terminal or monomethylated
double bond, respectively, and are unreactive (Table 1, en-
tries 1 and 2). No conversion was observed in the absence of
ruthenium catalyst (Table 1, entry 6). Stoichiometric NMR
spectroscopic experiments showed no transformation or ac-
tivation of the nucleophiles 3a–c by complex 1a in the ab-
sence of the alcohol.[6]
Catalytic transformations of terminal secondary substrates:
We found that 1-phenylpent-1-en-4-yn-3-ol (2c) reacted
with 1,3-cyclohexanedione (3b) in the presence of catalyst
1a and a catalytic amount of trifluoroacetic acid (TFA) to
yield 4cb as the sole product (Scheme 4). Thus, redox iso-
merization of the propargyl unit seems to be the preferred
initial reaction.
Surprisingly, complex product mixtures were observed
when other nucleophiles were used (Scheme 5, Table 1).
In the absence of a suitable nucleophile, terminal secon-
dary substrates such as 2c are converted to dienones by
Scheme 4. Transformation of 2c by redox isomerization, addition, and
cyclization.
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E. Haak et al.
redox isomerization. Subsequent formation of the spiro
compound 4cb occurs independently from the ruthenium
catalyst (Scheme 6). Closely related conversions of dienones
have been previously reported.[7]
Scheme 6. Transformation of 2c in the absence of a suitable nucleophile.
Whether the redox isomerization products (4 and 8) or
the cyclic products 5–7 are favored seems to depend on the
acidity of the nucleophile and the reaction medium. This re-
flects the role of the alcohol; the hydroxyl group assists 1,2-
hydrogen migration by electron donation in the redox iso-
merization and acts as a leaving group in the cyclization
pathway.[4b,5] Furthermore, the selectivity is strongly influ-
enced by the substitution pat-
Scheme 7. Ruthenium-catalyzed transformation of internal secondary
substrates.
tern of the catalyst.[4d] Our pre-
Table 2. Conversion of internal secondary substrates 2.
vious studies indicated that
complexes of type 1 catalyze
redox isomerization with termi-
nal alkyne substrates only.[4a,d]
Therefore, we expected higher
chemoselectivity with internal
alkyne substrates by exclusion
of the redox isomerization
pathway.
Entry
2
R1
R2
Products obtained (yield [%]) with nucleophile 3
3a
3b
3c
1
2
3
4
2d
2e
2 f
2g
H
H
Me
Ph
Ph
Me
Me
n.c.[a]
n.c.
n.c.
n.c.
n.c.
n.c.
5 fa (55)
5ga (58)
(E)-9ga (31)
5ha (61)
(E)-9ha (23)
5 fb (63)
5gb (59)
7gb (16, d.r.=6:1)
5hb (55)
7hb (13, d.r.=3:1)
5 fc (59)
5gc (62)
7gc (29, d.r.=3:2)
5hc (57)
7hc (tr)[b]
(E)-9hc (25)
n.p.
1-cyclohexenyl
5
2h
Ph
Me
6[c]
7[e]
2h
2h
Ph
Ph
Me
Me
n.p.[d]
5hb (tr)
5ha (60)
5hb (49)
n.p.
Catalytic transformations of in-
ternal secondary substrates: Re-
actions of internal secondary
substrates lead to the formation
of pyran compounds 5 as the
major products (Scheme 7,
Table 2). This is in accordance
with the previously reported
analogous transformation of ar-
omatic secondary propargyl al-
(E)-9ha (21)
5ia (51%)
(E)-9ia (29)
7hb (28, d.r.=6:1)
5ib (57)
8
2i
Ph
n-hexyl
5ic (65)
7ic (tr)
(E)-9ic (tr)
5jc (48)
(E)-9jc (31)
n.p.
9
2j
2j
Ph
Ph
Ph
Ph
5ja (49)
(E)-9ja (33)
n.p.
5jb (61)
7jb (25, d.r.=5:4)
5jb (tr)
10[c]
[a] n.c.=No conversion. [b] tr=trace. [c] Reaction performed without TFA. [d] n.p.=Reaction not performed.
[e] Reaction performed with Ru catalyst 1b.
cohols with internal alkyne groups (same nucleophiles, reac-
tion conditions, and catalysts but different substrates).[4b]
Aryl- or alkyl-substituted educts are suitable substrates, but
compounds with a terminal double bond remain unreactive
(Table 2, entries 1 and 2). The reaction strongly depends on
the presence of the acidic additive (Table 2, entry 6 and 10).
The results obtained with catalyst 1b are very similar to
those obtained with 1a (Table 2, entry 7). The sterically fa-
vored E-configured enynes (E)-9 or their cyclization prod-
ucts 7 (major isomer=trans) are observed as byproducts.
The trans selectivity may result from a 5-exo-trig cyclization
of 9 that occurs from the less-hindered face.
Scheme 8. Transformation of 2h in the absence of ruthenium catalyst or
in the absence of a suitable nucleophile.
furan compound 7hb, respectively. Internal secondary sub-
strates are not transformed in the absence of a suitable nu-
cleophile (Scheme 8b).
The reactions of 2g that lead to pyran compounds 5 can
easily be coupled with a cycloaddition step. In presence of
The nucleophile is propargylated (I) or allylated (II) by
substrate 2hb under acidic conditions in the absence of the
ruthenium catalyst (Scheme 8a). Subsequent ruthenium-cat-
alyzed cyclization of I or II leads to pyran compound 5hb or
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Ruthenium-Catalyzed Allylation–Cyclization Reactions
FULL PAPER
Scheme 9. Propargylation–cyclization–cycloaddition cascade.
N-phenyl maleimide the polycyclic compounds 10 are
formed as single diastereomers from 2g in a one-pot cascade
sequence (Scheme 9). The coupling constants in the NMR
spectra of products 10 indicate that the cycloaddition occurs
exo and anti with respect to the styrene substituent.
Scheme 10. Ruthenium-catalyzed transformation of terminal tertiary sub-
strates.
Table 3. Conversion of terminal tertiary substrates 2.
Catalytic transformations of terminal tertiary sub-
strates: A remarkably different reaction outcome is
observed for terminal tertiary substrates; spirocy-
Entry
2
R1
R2 R3
Products obtained (yield [%]) with nucleophile 3
3a
3b
3c
1
2k
2k
H
H
H
H
Me 5ka (8)
6ka (78)
Me 6ka (75)
5kb (5)
6kc (91)
clopentenes
6
become the major products
6kb (82)
2[a]
5kb (tr)[b]
n.p.[c]
(Scheme 10, Table 3). This is particularly notewor-
thy because the analogous conversion of simple ter-
tiary propargyl alcohols that possessed a terminal
alkyne group was previously shown to give pyran
compounds with high selectivity.[4b] Aryl- or alkyl-
substituted educts are suitable substrates and this
reaction also occurs with compounds that contain a
terminal double bond (Table 3, entries 1 and 2). In-
creasing steric hindrance leads to lower yields and
more byproduct formation, especially with nucleo-
phile 3b (Table 3, entries 8–10), whereas rigid eny-
nols that contain exocyclic double bonds (such as
2p) give the highest yields and selectivities
(Scheme 11). The acidic additive promotes higher
yields and is crucial in some cases (Table 3, entries 2
and 5). When catalyst 1b was used spirocyclopen-
tene 6lb became the minor product from cyclization
with 3b (Table 3, entry 6). The only side products
observed with nucleophile 3a were small amounts
of pyran compounds 5. With nucleophiles 3b or 3c
compounds 7 (formed as mixtures of trans diaster-
eomers only) become the major byproducts, some-
times accompanied by small amounts of their iso-
meric allenes 11 and dihydrofurans 12. The ob-
6kb (66)
7kb (5, d.r.=5:4)
n.c.
6lb (49)
7lb (29, d.r.=3:2)
12lb (9)
6lb (tr)
7lb (30, d.r.=3:2)
6lb (7)
3[d]
4
2k
2l
H
Ph
H
H
Me n.c.[e]
Me 5la (8)
6la (81)
n.p.
6lc (90, d.r.=5:4)
5[a]
6[f]
2l
2l
Ph
Ph
H
H
Me 6la (79)
n.p.
n.p.
Me n.p.
7lb (62, d.r.=3:2)
12lb (9)
7[d]
8
2l
Ph
H
H
Me n.p.
11lb (10, single ds[g]
12lb (14)
)
n.p.
2m Me
Et
6ma (29) 7mb (42, d.r.=5:4)
12mb (tr)
6mc (32, d.r.=5:4)
7mc (35, d.r.=3:2)
12mc (18)
6nc (62, d.r.=7:1)
12nc (27)
6oc (70, d.r.=4:3)
7oc (16, d.r.=3:2)
11oc (7, single ds)
12oc (5)
À
C4H8
À
À
9
2n
2o
Me 5na (31)
6na (tr)
Me 5oa (16)
6oa (39)
7nb (tr)
12nb (12)
7ob (26, d.r.=2:1)
11ob (16, single ds)
À
C3H6
10
12ob (33)
[a] Reaction performed without TFA. [b] tr=trace. [c] n.p.=Reaction not performed.
[d] Reaction performed without Ru catalyst. [e] n.c.=No conversion. [f] Reaction per-
formed with Ru catalyst 1b. [g] ds=Diastereoisomer.
served trans selectivity may be rationalized by
5-exo-trig cyclization of an initially formed enyne 9 that
occurs from the less-hindered face. Aliphatic substrates are
not converted in absence of the ruthenium catalyst (Table 3,
entry 3), whereas small amounts of byproducts 11 and 12
are slowly generated under acidic conditions from some aro-
matic derivatives (Table 3, entry 7).
In absence of a suitable nucleophile, terminal tertiary sub-
strates undergo formal allylic rearrangement (Sche-
a
me 12a). In some cases, the rearranged alcohol may cyclise
to form the corresponding furan (Scheme 12b). Because
traces of CO-shortened dienes are observed as byproducts
this transformation may involve an allenylidene intermedia-
te.[4a–b,d,8] In addition, small amounts of Diels–Alder adducts
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E. Haak et al.
Scheme 11. Transformation of benzylidene derivative 2p.
Scheme 13. Ruthenium-catalyzed transformation of dimethyl derivative
2q.
Scheme 12. Transformation of 2k and 2l in the absence of a suitable nu-
cleophile.
that result from initial dehydration are observed in some
cases.
A different reaction outcome is observed with substrates
that are disubstituted at the distal carbon atom of the
double bond (Scheme 13). Terminal tertiary substrate 2q
leads to bicyclic acetals 13, obtained as single diastereomers
that could be derived from an intermediate dihydrofuran
(A). The intermediate A may be formed by allylic rear-
rangement of 2q followed by cyclization of the rearranged
enynol. Compounds 12 are the only byproducts formed after
reaction with nucleophile 3b or 3c. Reaction with nucleo-
phile 3a results in furan 14qa as the major byproduct, plus
compounds 5qa and 6qa. Compound 14qa may be derived
from A or from 6qa.
Scheme 14. Ruthenium-catalyzed transformation of internal tertiary sub-
strates.
is still under investigation. A related ruthenium-catalyzed
isomerization of unactivated alkynes to give 1,3-dienes has
been reported by Mitsudo and co-workers.[9] Nucleophiles 3
are slowly allylated by internal tertiary substrates in the ab-
sence of the ruthenium catalyst under acidic conditions
Catalytic transformations of in-
ternal tertiary substrates: Final-
Table 4. Conversion of internal tertiary substrates 2.
ly, internal tertiary substrates
allylate nucleophiles 3 to yield
the sterically less-hindered Z
enynes (Z)-9 or their cycliza-
tion products 7, again as mix-
tures of trans diastereomers
(Scheme 14, Table 4). The use
of catalyst 1b leads to similar
results (Table 4, entry 2). In
some cases the isomeric dienes
15 are formed as either E,Z or
Z,Z isomers (Table 4, entry 5).
Entry
2
R1
R2
R3
Products obtained (yield [%]) with nucleophile 3
3a
3b
3c
1
2r
2r
Ph
Ph
Me
Me
Me
Me
(Z)-9ra (87)
7rb (88, d.r.=4:1)
(Z)-12rb (7)
7rb (82, d.r.=3:2)
(Z)-12rb (8)
(Z)-9rb (64)
(Z)-9sb (76)
7sb (tr)[d]
7rc (48, d.r.=3:2)
(Z)-9rc (26)
n.p.
2[a]
n.p.[b]
3[c]
4
2r
2s
Ph
Ph
Me
Me
Me
Ph
n.p.
Z-9sa (86)
n.p.
7sc (49, d.r.=5:4)
(Z)-9sc (46)
(Z)-9tc (62)
5
2t
Ph
Me
n-hexyl
(Z)-9ta (67)
(E)-9ta (15)
(Z)-9tb (76)
7tb (tr)
AHCTUNGTRENNUNG
15tb (tr)
ACHTUNGTRENNUNG
[a] Reaction performed with Ru catalyst 1b. [b] n.p.=Reaction not performed. [c] Reaction performed with-
The latter isomerization process out Ru catalyst. [d] tr=trace.
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Ruthenium-Catalyzed Allylation–Cyclization Reactions
FULL PAPER
(Table 4, entry 3). Ruthenium-catalyzed cyclization of 9rb
leads to furan compound 7rb.
In the absence of a suitable nucleophile internal tertiary
substrates form Diels–Alder adducts after an initial dehy-
dration step (Scheme 15).
Scheme 15. Transformation of 2r in the absence of a suitable nucleophile.
Overall mechanism: In agreement with our previously re-
ported studies,[4] we assume that coordination of the chelat-
ing substrate leads to the activated p complex A, which re-
mains relatively stable in the presence of an internal alkyne
in the substrate. Attack of the nucleophile 3 generates p
complexes B and C by loss of water, with C predominantly
formed from internal secondary substrates 2. Product 7
(major product from internal tertiary substrates) and by-
products 11 and 15 are formed from B by a 5-exo-trig cycli-
zation, whereas compound 9 is formed by direct decomplex-
ation. 6-Endo-dig cyclization from complex C leads to prod-
uct 5 (major product from internal secondary substrates),
whereas the 5-exo-dig cyclization generates byproduct 12. In
the case of substrates with a terminal alkyne group p com-
plex A is in equilibrium with alkynyl complex D and vinyli-
dene species F. This equilibrium is supported by labeling ex-
periments[4a] and similar equilibria reported previously.[2,8c]
Alkynyl complex D derived from terminal secondary sub-
strates may undergo a 1,2-hydrogen shift to generate trans-
alkenyl complex E by intramolecular protonation of the
triple bond. Subsequent nucleophilic attack leads to the
redox isomerization products 4 and 8 (major products from
terminal secondary substrates). A similar direct 1,2-hydro-
gen shift from p-complexed propargyl alcohols was previ-
ously observed with more-electron-poor ruthenium frag-
ments and cannot be excluded.[4d–e,5] Nevertheless, we be-
lieve that initial formation of alkynyl species D is crucial
when catalysts of type 1 are used because redox isomeriza-
tion does not occur with internal secondary substrate and la-
beling studies indicate the occurrence of alkynyl intermedia-
tes.[4a] Terminal tertiary substrates may easily form allenyli-
dene species G from vinylidene complex F. Nucleophilic
attack and 5-enol-exo-exo-dig cyclization generates product
6 as the major product via alkynyl species H. The occur-
rence of allenylidene intermediates is supported by the for-
mation of CO-shortened byproducts from substrates with a
terminal alkyne moiety (Scheme 12) and by previously re-
ported results.[4,8] It cannot be excluded that all byproducts
formed from substrates with a terminal alkyne could also be
generated via allenylidene intermediate G (Scheme 16).
Scheme 16. Proposed mechanisms for the catalytic transformations.
Conclusion
We presented several selective and atom-economic transfor-
mations of 1-vinyl propargyl alcohols 2 with cyclic 1,3-dicar-
bonyl compounds 3 catalyzed by ruthenium complexes of
redox-coupled cyclopentadienone ligands. The reaction
pathway depends on the substitution pattern of the alcohol.
Three fundamentally different modes of activation can be
distinguished. Terminal secondary substrates form alkenyl
complexes by a 1,2-hydrogen shift, whereas the transforma-
tions of terminal tertiary substrates involve allenylidene in-
termediates. Substrates with internal alkynes are directly
converted via an activated p complex. The overall reactions
lead to the formation of highly substituted furans, pyrans,
and five- or six-membered spirocarbocycles from 2 and the
binucleophilic reaction partner 3 by cascade allylation–cycli-
zation sequences. All presented catalytic transformations
were performed with a single precatalyst and generate water
as the only waste product. Coupling of some of the catalytic
transformations with a cycloaddition step in a one-pot proc-
ess allows the selective synthesis of highly functionalized
polycyclic compounds. Further investigations with regard to
the reaction mechanisms, scope, and limitation that focus on
sequential catalyzed processes and asymmetric catalytic ap-
plications by use of axially chiral members of the complex
series 1 are currently under investigation.
Experimental Section
General methods: All reactions were carried out under a dry argon at-
mosphere by using standard Schlenk techniques. The chemicals used
were dried and purified by common procedures. Products were identified
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E. Haak et al.
by spectroscopic analysis (1H NMR, 13C NMR, IR, MS, HRMS). Infrared
spectra were recorded on a Perkin–Elmer FTIR 2000 spectrometer.
NMR spectra were recorded on a Bruker DPX 400 or a Bruker Avance
600 spectrometer. MS and HRMS data were obtained with a Finnigan
MAT 95 mass spectrometer. Data for catalysts 1a and 1b have previously
been published.[4a,c–d]
2H), 2.50–2.61 (m, 2H), 2.63–2.76 (m, 1H), 4.34 (brd, J=4.2 Hz, 1H),
4.39 (dd, J=7.6, 4.4 Hz, 1H), 7.18–7.31 ppm (m, 5H); 13C NMR
(100 MHz, DEPT, CDCl3): d=3.4 (CH3), 16.9 (CH3), 21.8 (CH2), 24.0
(CH2), 31.8 (CH), 36.8 (CH2), 48.5 (CH), 78.4 (C), 78.5 (C), 96.0 (CH),
116.6 (C), 126.7 (CH), 127.1 (CH), 128.5 (CH), 142.8 (C), 176.9 (C),
194.7 ppm (C).
General catalytic procedure: Catalyst 1a or 1b (0.02 mmol) was dissolved
in toluene (1 mL). TFA (0.02 mmol) diluted in toluene (1m), propargyl
Compound 10gc (single diastereoisomer): 1H NMR (400 MHz, CDCl3):
d=1.37–1.60 (m, 2H), 1.70–2.00 (m, 4H), 2.45–2.53 (m, 1H), 2.56–2.63
(m, 1H), 2.66–2.74 (m, 1H), 3.02–3.07 (ddd, J=10.2, 5.2, 2.8 Hz, 1H),
3.26 (t, J=7.8 Hz, 1H), 3.54 (dd, J=7.9, 5.9 Hz, 1H), 4.64 (dd, J=8.7,
4.9 Hz, 1H), 6.21 (dd, J=15.7, 8.7 Hz, 1H), 6.71 (d, J=15.7 Hz, 1H),
7.05–7.36 (m, 12H), 7.50 (td, J=7.8, 1.6 Hz, 1H), 7.86 ppm (dd, J=7.9,
1.6 Hz, 1H); 13C NMR (100 MHz, DEPT, CDCl3): d=22.6 (CH2), 23.1
(CH2), 23.4 (CH2), 26.4 (CH2), 33.4 (CH), 36.8 (CH), 37.1 (CH), 43.6
(CH), 44.8 (CH), 103.5 (C), 114.8 (C), 116.6 (CH), 118.4 (C), 122.2 (CH),
123.8 (CH), 126.2 (CH), 126.3 (CH), 127.4 (CH), 128.4 (CH), 128.5
(CH), 129.0 (CH), 129.8 (CH), 131.2 (CH), 131.4 (C), 131.7 (CH), 136.7
(C), 138.8 (C), 152.5 (C), 155.3 (C), 161.0 (C), 175.8 (C), 175.9 ppm (C);
IR: n˜ =3019 (m), 2936 (m), 2860 (m), 1712 (s), 1637 (s), 1611 (s), 1573
(m), 1495 (s), 1456 (m), 1385 (s), 1328 (m), 1274 (m), 1216 (s), 1195 (s),
1107 (m), 1031 (m), 965 (m), 906 (m), 755 (s), 693 (m), 667 cmÀ1 (m); MS
(EI): m/z (%)=555 [M+] (10), 381 (100), 328 (18), 121 (16), 91 (14);
HRMS: m/z calcd for C36H29NO5: 555.2046 [M+]; found: 555.2046.
alcohol
2 (1 mmol), and nucleophile 3 (1 mmol) were subsequently
added. The mixture was stirred at 1008C for 5 h under argon. Evapora-
tion of the solvent and flash chromatography on silica furnished the puri-
fied product as a colorless oil or foam.
Compound 4cb: 1H NMR (400 MHz, CDCl3): d=1.17–1.27 (m, 1H),
1.65–1.75 (m, 1H), 2.07–2.57 (m, 8H), 2.82 (ddd, J=16.1, 12.1, 6.5 Hz,
1H), 3.49 (t, J=14.6 Hz, 1H), 3.77 (dd, J=14.0, 4.2 Hz, 1H), 7.05–
7.29 ppm (m, 5H); 13C NMR (100 MHz, DEPT, CDCl3): d=15.7 (CH2),
31.5 (CH2), 36.5 (CH2), 39.4 (CH2), 40.6 (CH2), 43.1 (CH2), 48.2 (CH),
64.7 (C), 127.7 (CH), 128.1 (CH), 128.6 (CH), 138.7 (C), 209.5 (C), 211.1
(C), 211.5 ppm (C); IR: n˜ =3060 (m), 3030 (m), 2927 (s), 1715 (s), 1689
(s), 1604 (s), 1494 (m), 1453 (m), 1384 (s), 1231 (m), 1178 (m), 1031 (m),
916 (m), 760 (m), 701 cmÀ1 (s); MS (EI): m/z (%)=270 [M+] (60), 242
(57), 211 (60), 212 (68), 104 (100); HRMS: m/z calcd for C17H18O3:
270.1256 [M+]; found: 270.1256.
Compound 13qa (single diasteroisomer): 1H NMR (600 MHz, CDCl3):
d=0.92 (d, J=6.7 Hz, 3H), 1.22 (s, 3H), 1.29 (s, 3H), 1.55 (s, 3H), 2.53–
2.56 (m, 4H), 2.61 (qd, J=6.7, 3.6 Hz, 1H), 2.66 ppm (d, J=3.6 Hz, 1H);
13C NMR (150 MHz, DEPT, CDCl3): d=10.3 (CH3), 21.1 (CH3), 25.4
(CH2), 25.5 (CH3), 26.5 (CH3), 34.3 (CH2), 38.2 (CH), 43.1 (CH), 90.1
(C), 111.6 (C), 117.0 (C), 184.3 (C), 202.6 ppm (C); IR: n˜ =2975 (m),
2932 (m), 2871 (w), 1683 (s), 1618 (s), 1504 (m), 1440 (m), 1404 (s), 1389
(s), 1340 (m), 1306 (m), 1261 (m), 1236 (m), 1195 (m), 1155 (m), 1128
(w), 923 (w), 837 (w), 801 (w), 755 (s), 701 (m), 666 cmÀ1 (w); MS (EI):
m/z (%)=222 [M+] (35), 207 (100), 171 (45), 157 (38), 143 (72), 129
(98); HRMS: m/z calcd for C13H18O3: 222.1256 [M+]; found: 222.1256.
Compound 5ic: 1H NMR (400 MHz, CDCl3): d=0.93 (t, J=7.3 Hz, 3H),
1.24–1.46 (m, 6H), 1.68 (quint, J=7.5 Hz, 2H), 2.39 (t, J=7.6 Hz, 2H),
4.17 (dd, J=5.7, 5.3 Hz, 1H), 5.05 (d, J=5.6 Hz, 1H), 6.43 (dd, J=15.9,
6.5 Hz, 1H), 6.54 (d, J=15.9 Hz, 1H), 7.26–7.38 (m, 7H), 7.55 (td, J=
7.3, 1.6 Hz, 1H), 7.82 ppm (dd, J=7.6, 1.6 Hz, 1H); 13C NMR (100 MHz,
DEPT, CDCl3): d=14.1 (CH3), 22.6 (CH2), 26.5 (CH2), 28.7 (CH2), 31.5
(CH2), 32.6 (CH), 32.7 (CH2), 101.1 (CH), 102.7 (C), 114.6 (C), 116.6
(CH), 122.5 (CH), 124.0 (CH), 126.4 (CH), 127.4 (CH), 128.4 (CH),
130.9 (CH), 131.1 (CH), 131.8 (CH), 136.9 (C), 150.6 (C), 152.5 (C),
156.1 (C), 162.0 ppm (C); IR: n˜ =3061 (m), 3027 (m), 2955 (s), 2929 (s),
2858 (m), 1719 (s), 1630 (s), 1610 (s), 1570 (m), 1494 (s), 1455 (s), 1411
(m), 1390 (s), 1328 (m), 1273 (m), 1211 (s), 1185 (s), 1150 (m), 1106 (m),
1034 (m), 983 (w), 971 (w), 909 (m), 757 (s), 733 (s), 698 cmÀ1 (s); MS
(EI): m/z (%)=386 [M+] (100), 262 (62), 121 (57); HRMS: m/z calcd for
C26H26O3: 386.1882 [M+]; found: 386.1884.
[1] Selected reviews: a) M. Bartlett, Chem. N. Z. 2012, 76, 11–16; b) P. J.
Dunn in Pharmaceutical Process Research & Development: Current
Chemical and Engineering Challenges (Eds.: J. Blacker, M. T. Wil-
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in Handbook of Green Chemistry, Vol. 1 (Eds.: P. T. Anastas, R. H.
Crabtree), Wiley-VCH, Weinheim, 2009, pp. 1–15; d) C.-J. Li, B. M.
Trost, Proc. Natl. Acad. Sci. USA 2008, 105, 13197–13202; e) R. A.
Sheldon, Chem. Commun. 2008, 3352–3365; f) B. M. Trost in Transi-
tion Metals for Organic Synthesis (Eds.: M. Beller, C. Bolm), Wiley-
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2002, 35, 695–705; h) B. M. Trost, Angew. Chem. 1995, 107, 285–307;
Angew. Chem. Int. Ed. Engl. 1995, 34, 259–281; i) B. M. Trost, Science
1991, 254, 1471–1477.
[2] Selected reviews: a) V. Cadierno, J. Gimeno, Chem. Rev. 2009, 109,
3512–3560; b) C. Bruneau, P. H. Dixneuf, Angew. Chem. 2006, 118,
2232–2260; Angew. Chem. Int. Ed. 2006, 45, 2176–2203; c) C. Bru-
neau, S. Dꢃrien, P. H. Dixneuf, Top. Organomet. Chem. 2006, 19,
295–326; d) B. M. Trost, M. U. Frederiksen, M. T. Rudd, Angew.
Chem. 2005, 117, 6788–6825; Angew. Chem. Int. Ed. 2005, 44, 6630–
6666; e) V. Cadierno, M. P. Gamasa, J. Gimeno, Coord. Chem. Rev.
2004, 248, 1627–1657; f) Topics in Organometallic Chemistry, Vol. 11,
Ruthenium Catalysts and fine chemistry (Eds: C. Bruneau, P. H. Dix-
neuf), Springer, Heidelberg, 2004.
1
Compound 6la: H NMR (600 MHz, CDCl3): d=1.96 (t, J=1.8 Hz, 3H),
2.04 (ddd, J=18.9, 12.0, 8.4 Hz, 1H), 2.53 (ddd, J=18.9, 10.9, 5.2 Hz,
1H), 2.74 (ddd, J=19.3, 10.9, 8.4 Hz, 1H), 2.89 (ddd, J=19.3, 12.0,
5.2 Hz, 1H), 4.41 (brs, 1H), 4.55 (brs, 1H), 5.09 (brs, 1H), 5.89 (brs,
1H), 7.11–7.31 ppm (m, 5H); 13C NMR (150 MHz, DEPT, CDCl3): d=
12.5 (CH3), 36.3 (CH2), 36.4 (CH2), 59.3 (CH), 73.1 (C), 105.4 (CH2),
127.9 (CH), 128.6 (CH), 128.7 (CH), 134.4 (CH), 137.8 (C), 141.6 (C),
153.8 (C), 210.7 (C), 213.5 ppm (C); IR: n˜ =3061 (w), 3028 (w), 2920 (m),
1723 (s), 1668 (m), 1620 (m), 1495 (m), 1453 (m), 1417 (m), 1343 (w),
1279 (w), 1250 (m), 1204 (m), 1187 (m), 1110 (w), 1079 (w), 1031 (w), 967
(w), 913 (w), 876 (w), 776 (w), 752 (m), 733 (m), 702 cmÀ1 (s); MS (EI):
m/z (%)=252 [M+] (100), 237 (38), 209 (49), 181 (40), 152 (37), 91 (58);
HRMS: calcd for C17H16O2: 252.1150 [M+]; found: 252.1150.
Compound 7rb
Major diastereoisomer: 1H NMR (400 MHz, CDCl3): d=1.19 (d, J=
7.2 Hz, 3H), 1.78 (d, J=2.0 Hz, 3H), 2.06–2.13 (m, 2H), 2.26–2.41 (m,
2H), 2.51–2.63 (m, 2H), 2.76–2.82 (m, 1H), 4.25 (brd, J=5.2 Hz, 1H),
4.50 (dd, J=5.2, 4.4 Hz, 1H), 7.18–7.31 ppm (m, 5H); 13C NMR
(100 MHz, DEPT, CDCl3): d=3.5 (CH3), 16.2 (CH3), 21.8 (CH2), 23.9
(CH2), 31.3 (CH), 36.8 (CH2), 48.2 (CH), 77.9 (C), 78.3 (C), 95.3 (CH),
116.6 (C), 126.7 (CH), 127.2 (CH), 128.6 (CH), 142.6 (C), 177.6 (C),
194.5 ppm (C); NOESY (600 MHz, CDCl3): cross peaks d=1.19/4.25,
2.79/4.25, 4.50/7.20 ppm; IR: n˜ =3029 (w), 2975 (m), 2946 (m), 2921 (m),
2978 (m), 1634 (s), 1494 (w), 1454 (m), 1422 (m), 1398 (s), 1375 (m), 1247
(m), 1228 (m), 1180 (s), 1058 (w), 1005 (w), 944 (m), 913 (s), 733 (s), 700
(m), 647 cmÀ1 (w); MS (EI): m/z (%)=280 [M+] (100), 265 (24), 213
(61), 212 (42), 128 (40), 105 (60); HRMS: m/z calcd for C19H20O2:
280.1463 [M+]; found: 280.1463.
[3] Selected examples: a) B. M. Trost, A. Breder, Org. Lett. 2011, 13,
398–401; b) C. S. Yi, J. Organomet. Chem. 2011, 696, 76–80; c) T.
Kondo, Bull. Chem. Soc. Jpn. 2011, 84, 441–458; d) V. Cadierno, J.
Dꢄez, J. Gimeno, N. Nebra, J. Org. Chem. 2008, 73, 5852–5858; e) V.
Cadierno, P. Crochet, J. Gimeno, Synlett 2008, 1105–1124; f) V. Ca-
dierno, P. Crochet, Current. Org. Synth. 2008, 5, 343–364; g) Y.
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guez, S. G. Rubin, L. Castedo, C. Saꢅ, Pure Appl. Chem. 2008, 80,
Minor diastereoisomer: 1H NMR (400 MHz, CDCl3): d=1.22 (d, J=
7.2 Hz, 3H), 1.78 (d, J=2.0 Hz, 3H), 2.04–2.12 (m, 2H), 2.26–2.43 (m,
15510
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Chem. Eur. J. 2012, 18, 15504 – 15511

Ruthenium-Catalyzed Allylation–Cyclization Reactions
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Received: July 6, 2012
Published online: October 5, 2012
Chem. Eur. J. 2012, 18, 15504 – 15511
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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