Synthesis of β-hydroxy and β-amino ketones from allylic alcohols catalyzed by ru(η5-C5Ph5)(CO)2Cl

Article abstract of DOI:10.1002/ejic.201101014

An efficient method for the synthesis of β-hydroxy and β-amino ketones from allylic alcohols catalyzed by Ru(η⁵-C ₅Ph₅)(CO)₂Cl is described. The influence of the stereoelectronic properties of the catalyst on the reaction outcome has been studied. Optimization of the reaction conditions supressed the formation of undesired side products such as saturated ketones, benzyl alcohols, and α,β-unsaturated ketones. Several aromatic and aliphatic allylic alcohols have been reacted with a large variety of aldehydes or imines to produce β-hydroxy ketones or β-amino ketones, respectively, in yields up to 99a%. Based on experimental data, a mechanism via ruthenium alkoxides and ruthenium aldoxides is proposed. In addition, a C-bound ruthenium enolate has been characterized. β-Hydroxy and β-amino ketones are synthesized from allylic alcohols and aldehydes or imines, respectively. The coupling reaction is catalyzed by Ru(η⁵-C₅Ph₅)(CO) ₂Cl. Mechanistic investigations support a mechanism via ruthenium alkoxide intermediates.

Full text of DOI:10.1002/ejic.201101014

FULL PAPER
DOI: 10.1002/ejic.201101014
Synthesis of β-Hydroxy and β-Amino Ketones from Allylic Alcohols Catalyzed
by Ru(η5-C5Ph5)(CO)2Cl
Agnieszka Bartoszewicz,[a,b] Martina M. Jezowska,[a] Kévin Laymand,[a] Juri Möbus,[a] and
˙
Belén Martín-Matute*[a,b]
Keywords: Synthetic methods / Homogeneous catalysis / Ruthenium / Isomerization / Allylic alcohols / Amines / Mannich
reaction / Aldols / Ketones
An efficient method for the synthesis of β-hydroxy and β-
amino ketones from allylic alcohols catalyzed by Ru(η5-
C5Ph5)(CO)2Cl is described. The influence of the stereoelec-
tronic properties of the catalyst on the reaction outcome has
been studied. Optimization of the reaction conditions sup-
ressed the formation of undesired side products such as satu-
rated ketones, benzyl alcohols, and α,β-unsaturated ketones.
Several aromatic and aliphatic allylic alcohols have been re-
acted with a large variety of aldehydes or imines to produce
β-hydroxy ketones or β-amino ketones, respectively, in yields
up to 99%. Based on experimental data, a mechanism via
ruthenium alkoxides and ruthenium aldoxides is proposed.
In addition, a C-bound ruthenium enolate has been charac-
terized.
have recently reported the iridium-catalyzed conversion of
allylic alcohols to α-fluoro ketones, which was achieved
with an electrophilic fluorinating reagent.[7]
Introduction
Metal enolates are very important intermediates in syn-
thetic organic transformations in which C–C or C–hetero-
atom bonds are formed.[1] Enolates of transition metals
have emerged as synthetically appealing alternative interme-
diates to enolates of main group elements. Methods to pre-
pare transition metal enolates[2] include the reduction of en-
ones by hydrogen or silane mediated by rhodium and other
transition metals.[3] These intermediates can also be pre-
pared from allylic alcohols in a process whereby an internal
redox reaction is catalyzed by the metal complex.[4] Both
methods have been used in the formation of C–C bonds in
the presence of aldehydes or imines (Scheme 1).[3,5,6] We
The transition-metal-catalyzed coupling of allylic
alcohols with aldehydes or imines has been hampered by its
moderate efficiency, which is due to the formation of vari-
able amounts of unsubstituted ketones by isomerization of
the allylic alcohols (i.e. reaction with the electrophile, alde-
hyde or imine, did not occur; E = H in Scheme 1).[4] In
2006, an important breakthrough was achieved when Grée
and co-workers reported the use of nickel hydride com-
plexes in the coupling of allylic alcohols with aldehydes to
obtain aldols in high yields.[5m] The same group have re-
cently reported the use of N-sulfonylimines and N-tert-bu-
tanesulfinimines as electrophiles with Fe and Ni complexes,
respectively.[5m,5o] In the latter case, the tandem isomeriza-
tion/Mannich reaction was used as the key step in the
enantioselective synthesis of ent-nikkomycin and ent-funeb-
rine.[5o] Our own contributions, namely, the transition-
metal-catalyzed coupling of allylic alcohols with aldehydes
or imines, include the use of ruthenium[6a] and rhodium[6b]
catalyst systems [Ru(η5-C5Ph5)(CO)2Cl (1a) and [Rh-
(COD)Cl]2/PPh3 (COD = cyclooctadiene), respectively.
Complex 1a afforded aldol products in high yields under
mild reaction conditions. The rhodium system, on the other
hand, not only catalyzed the coupling of allylic alcohols
with aromatic aldehydes or imines efficiently, but also that
of homoallylic and bishomoallylic alcohols. One limitation
of both of these catalytic systems is their incompatibility
with aliphatic aldehydes as electrophiles, which afforded
aldol products through self-condensation reactions without
participation of the allylic alcohols.
Scheme 1. Synthesis of α-substituted ketones from enones or allylic
alcohols catalyzed by transition metal complexes.
[a] Department of Organic Chemistry, Stockholm University,
10691 Stockholm, Sweden
Fax: +46-8-154908
E-mail: belen@organ.su.se
[b] Berzelii Centre EXSELENT on Porous Materials, Stockholm
University,
10691 Stockholm, Sweden
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejic.201101014.
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Herein, we report our studies on the scope of the tandem the introduction of a MeO or NHiPr group on the cyclo-
isomerization/C–C bond formation catalyzed by 1a. The re- pentadienyl ligand (1f[9] and 1g,[10] Figure 1) did not afford
action has been extended to the use of aliphatic aldehydes, better results (Table 1, Entries 7 and 8). Substitution of the
α,β-unsaturated aldehydes and imines as electrophiles. We Cl ligand in 1a by Br or I (Figure 1, 1h[11] and 1i,[12] respec-
also report further mechanistic investigations.
tively) gave comparable results to those obtained with 1a
(Table 1, Entries 9–10 vs. 5).
Results and Discussion
Synthesis of β-Hydroxy Ketones (Aldols) – Scope and
Limitations
In our previous communication,[6a] we reported the ac-
tivity of a variety of ruthenium chloride complexes (1a–1d,
Figure 1) in the reaction between α-vinylbenzyl alcohol (2a)
and p-chlorobenzaldehyde (3a, Scheme 2). Activation of the
ruthenium chlorides was achieved by reaction with KOtBu,
which displaces the chloride ligand to form ruthenium tert-
butoxide intermediates.[8] Whereas commercially available
ruthenium chloride complexes Ru(PPh3)3Cl2 (1b) and
Ru(η5-Cp)(PPh3)2Cl (1c, Figure 1) afforded the desired
aldol 4 in low yields (27–31%) along with large amounts of
ketone byproduct 5a (Table 1, Entries 1–2), complexes 1a
and 1d, which have bulky pentasubstituted cyclopentadienyl
ligands, gave good results (Table 1, Entries 3–4). The best
results were achieved with 1a, which bears five phenyl
groups on the cyclopentadienyl ring (Entry 3). Further opti-
mization of the reaction conditions revealed that at a lower
temperature, 1a afforded quantitative yields of 4 (Table 1,
Entry 5). In order to examine the possibility of a catalytic
system that works in a wider temperature range, we have
synthesized a new catalyst (1e, Figure 1), which is similar to
1a and has an α-naphthyl substituent on the cyclopen-
tadienyl ring. Unfortunately, 1e afforded large amounts of
5a (Table 1, Entry 6). Other catalyst modifications, such as
Scheme 2. Coupling of 2a with 3a catalyzed by 1a–i.
Table 1. Catalyst screening.
Entry Catalyst Conversion [%][a]
t
4/5a[a]
syn/anti[a]
1
2
3
4
1b
1c
1a
1d
1a
1e
1f
1g
1h
1i
73
85
16 h
16 h
13 min
1.5 h
6 h
40 min
18 h
18 h
43:57
32:68
85:15
96:4
71:29
84:16
65:35
62:38
84:16
62:38
–
75:25
78:22
77:23
Ͼ 99
Ͼ 99
Ͼ 99
Ͼ 99
13
57
94
70
5[b]
6
99:1
63:37
50:50
91:9
87:13
97:3
7[b,c]
8[b]
9[b]
10[b]
18 h
18 h
[a] Measured by 1H NMR spectroscopic analysis of the crude reac-
tion mixtures. [b] 20 °C. [c] Together with 5a, several decomposition
products were formed.
Under the optimized reaction conditions (Table 1, Entry
5), a variety of allylic alcohols 2a–e were reacted with a
number of aromatic and aliphatic aldehydes (3a–p) to afford
aldols 4 and 6–24 in excellent yields (Scheme 3, Table 2),
and in most cases, under mild reaction conditions. In gene-
ral, the reaction of aromatic allylic alcohols (2a–c) with aro-
matic aldehydes (3a–f) proceeded smoothly regardless their
electronic properties (Table 2, Entries 1–6 and 9–10). The
presence of certain potentially coordinating groups, such as
4-methoxy or 1-furyl, did not affect the reaction rates
(Table 2, Entries 4 and 6). On the other hand, reactions
Figure 1. Ruthenium catalysts 1a–1i.
Scheme 3. Synthesis of 4 and 6–24 from 2a–e and 3a–p.
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Synthesis of Functionalized Ketones from Allylic Alcohols
Table 2. Coupling of allylic alcohols with aldehydes catalyzed by 1a.[a]
[a] Reactions conditions: KOtBu [56 μL, 0.5 m in tetrahydrofuran (THF), 7 mol-%] was added to a mixture of 1a (13 mg, 0.020 mmol,
5 mol-%) and Na2CO3 (42 mg, 0.4 mmol) in degassed toluene (1 mL) under a nitrogen atmosphere. The mixture was stirred for 3 min
before a solution of 2 (0.4 mmol) and 3 (0.6 mmol) in degassed toluene (1 mL) was added by syringe. [b] Determined by 1H NMR
spectroscopy of the crude mixture. In parenthesis, isolated yield of aldols. [c] At room temperature, 16 was obtained in 75% yield, syn/anti
80:20 after 24 h. [d] MS 4 Å were added instead of Na2CO3.
with aromatic aldehydes that contain cyano and pyridyl sively, and no further isomerization/aldolization was ob-
moieties were slower and had to be performed at higher served under the reaction conditions applied.[13] However,
temperatures (Table 2, Entries 7 and 8). Aliphatic alcohols when the reaction temperature was maintained for 3 h at
2d and 2e (Table 2, Entries 11–12) could also be used in the 35 °C and then raised to 100 °C for an additional 12 h,
coupling. In general, 2a–d, which have no substituents on aldol 20, formed from alcohol 2a and aldehyde 3l, was
the terminal carbon atom of the double bond, reacted much transformed into a mixture of 1,3-diketone 25 and 5a
faster than those that bear substituents (i.e. 2e). Catalyst (Scheme 4). Hence, this methodology offers an alternative
1a could also be used with α,β-unsaturated aldehydes. The to currently existing procedures[14] to synthesize 1,3-dicar-
resulting aldol products contain an allylic alcohol function- bonyl building blocks.[15] The reaction conditions had to be
ality that could potentially react further (Table 2, Entries modified in order to successfully couple aliphatic aldehydes,
13–18). These compounds, however, were formed exclu- which have hardly ever been used before in similar reac-
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B. Martín-Matute et al.
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tions.[5m] To avoid self-condensation of the highly reactive
aliphatic aldehydes under the reaction conditions, Na2CO3,
which was used before as a drying agent, was substituted by
molecular sieves (MS) 4 Å. Both aliphatic aldehydes used
(Table 2, Entries 19–20) afforded the corresponding aldols
in high yields with very high syn/anti ratios (up to 92:8).
This ratio is among the highest observed in this transforma-
tion. On the other hand, neither primary nor highly substi-
tuted allylic alcohols (e.g. 3-buten-1-ol, geraniol, 2-methyl-
3-buten-2-ol) gave any coupling product. In all successful
reactions, the new C–C bond was formed exclusively at the
carbon atom that originated from the double bond in the
starting allylic alcohol.
Scheme 5. Synthesis of β-amino ketones from 2a. Scope of the
imines.
Scheme 4. Tandem isomerization/aldol/isomerization reaction to
form 1,3-diketones.
Table 3. Scope of the imines in the coupling with 2a catalyzed by
1a.
Synthesis of β-Amino Ketones – Scope and Limitations
Entry Imine
β-Amino
ketone
β-Amino ketone/5[a] syn/anti[a]
We next investigated the use of imines as electrophiles
(Scheme 5). The products obtained, β-amino ketones, are
important intermediates in the synthesis of a variety of ni-
trogen-containing drugs and natural products.[16,17] Our
preliminary experiments that used 1a under identical reac-
tion conditions as those used with aromatic aldehydes (vide
supra) afforded β-amino ketones in low yields. Small
amounts of the imine substrates were hydrolyzed to the cor-
responding aldehydes, which participated in the coupling
reaction to yield β-hydroxy ketones. However, when we
used the reaction conditions employed with aliphatic alde-
hydes instead (i.e. replacement of Na2CO3 by MS 4 Å,
Table 2, Entries 19 and 20), imine hydrolysis was mini-
mized. We evaluated the reactivity of a variety of imines
(Scheme 5, Table 3) under the optimized conditions. N-aryl
aldimines[5g,18] 26a–c did not give the desired products
(Table 3, Entries 1–3), instead 2a was quantitatively isom-
erized into 5a. N-Boc-protected imine 26d (Table 3, Entry
4)[19] afforded side products as a result of a nucleophilic
attack of the hydroxy group in 2a to the Boc moiety. N-
Sulfonylaldimine 26e, on the other hand, gave good results
(Table 3, Entry 5) and produced β-amino ketone 31 in 90%
yield.[5n,6b,20] To study the influence of the N-sulfonlyl imine
structure on the reaction outcome, particularly on the dia-
stereoselectivity, in addition to N-tosyl imine 26e, we tested
two other N-sulfonyl imines: 6-methylnaphthyl- and 2-pyr-
idylsulfonylimines (26f and 26g, respectively). Increasing
the steric bulk of the imines, however, did not lead to an
improvement in the syn/anti ratio: 26f gave very similar re-
sults to those obtained with 26e (Table 3, Entry 6 vs. 5),
and the presence of an additional chelating group on the
imine 26g[21] suppressed the coupling reaction completely
(Table 3, Entry 7).
1
2
3
4
5
6
7
26a
26b
26c
26d
26e
26f
26g
27
28
29
30
31
32
33
0:100
0:100
0:100
20:80[b]
90:10
92:8
–
–
–
n.d.[c]
71:29
73:27
–
0:100
[a] Determined by 1H NMR spectroscopy. [b] Formation of side
products. [c] N.d. = not determined.
The best reaction conditions (35 °C, toluene, MS 4 Å, N-
tosyl imines, Table 3 Entries 5–6) were used to prepare a
number of β-amino ketones (31, 34–43, Scheme 6, Table 4).
Several aromatic imines that contained electron-donating
and -withdrawing substituents in ortho, meta, and para po-
sitions could be used (Table 4). The same alcohols that
worked well in aldol-type reactions could be coupled with
imines with equally good results (Table 4). The diastereo-
Scheme 6. Synthesis of β-amino ketones from allylic alcohols.
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Synthesis of Functionalized Ketones from Allylic Alcohols
selectivity was, however, poor with syn/anti ratios of up to Mechanistic Investigations
3:1. Only when 2f, which contains a large α-naphthyl sub-
To understand the reaction outcome observed at dif-
stituent, was used was a very good diastereomeric ratio (dr
= 86:14) obtained (Table 4, Entry 9).
ferent temperatures (vide supra, Table 1), we followed the
1
coupling between 2a and 3a catalyzed by 1a by H NMR
spectroscopy in [D8]toluene (Scheme 7 and Figure 2a–c). At
50 °C, 80% of 4 was produced after only 12 min (Figure 2,
a) and the formation of 5a was observed after 2 min. Inter-
estingly, after reaching a maximum yield of 80% (at
12 min), the amount of 4 decreased. Simultaneously, the
yield of 5a increased at a similar rate as that of the decom-
position of 4, which indicates that 5a can be formed not
only by Ru-catalyzed isomerization of the allylic alcohol
2a[4] but also from 4 by retroaldolization (Scheme 8 and
Supporting Information, page S10). It was also observed
that the syn/anti ratio of 4 was ca. 80:20 at the beginning
of the reaction and decreased as the coupling proceeded.
Table 4. Scope of the Mannich-type reaction catalyzed by 1a.[a]
Scheme 7. Reaction of 2a and 3a in [D8]toluene catalyzed by 1a at
different temperatures.
Similar kinetic data were obtained when the same experi-
ment was performed at 35 °C (Figure 2b), the difference be-
ing that 4 was formed in 99% yield within 30 min. In this
case, 5a was formed in minute amounts, even after pro-
longed reaction times (Ͻ3% within 90 min). Furthermore,
5a seems to form exclusively by retroaldolization as it
started to build up only after 2a had been consumed. The
syn/anti ratio was 81:19 for the first 10 min, after which
epimerization occurred until a thermodynamic mixture was
obtained (ca. 55:45 syn/anti). In the last experiment, per-
formed at room temperature (Figure 2c), 4 was exclusively
formed, although at a lower reaction rate, and retroaldol-
ization was suppressed, even with extended reaction times
(12 h). The rate of epimerization was significantly reduced
(the syn/anti ratio decreased from 94:6 to 84:16 after 6 h).
Interestingly, at 20 °C (Figure 2c) the plot of product for-
mation as a function of time produces a sigmoidal curve.
Such behavior is in agreement with recent studies on this
catalytic system that showed that 1a undergoes activation
through CO dissociation, which may be slower at 20 °C.[22]
From these plots, we conclude that the excellent results
obtained at 20 and 35 °C in the coupling of 2a with 3a
catalyzed by 1a (Figure 2b–c) can be ascribed to a dimin-
ished degradation of 4 (Table 1, Entry 5 vs. 3). This decom-
position occurred at 50 °C by retroaldolization to produce
5a from 4 (Scheme 8). Furthermore, the formation of 5a by
allylic alcohol isomerization was suppressed at mild reac-
tion conditions (25–35 °C).
[a] Reaction conditions: KOtBu (48 μL, 0.5 m in THF, 6 mol-%)
was added to a mixture of 1a (13 mg, 0.020 mmol, 5 mol-%) and
MS 4 Å (20 mg) in degassed toluene (1 mL) under a nitrogen atmo-
sphere. The mixture was stirred for 3 min before a solution of 2
(0.4 mmol) and 26 (0.44 mmol) in degassed toluene (1 mL) was
added by syringe. The mixture was stirred at 40 °C for the time
indicated. [b] Determined by 1H NMR spectroscopy. [c] Isolated
yield in parenthesis. [d] Reaction in THF.
1
Similarly, we followed the reaction of 2a with 26h by H
NMR spectroscopy (Scheme 9, Figure 3). In comparison to
the aldol reaction, which was finished within 30 min at
35 °C, the Mannich-type process was much slower and re-
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B. Martín-Matute et al.
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quired 3 h at 40 °C to reach full conversion. Formation of
β-amino ketone 34 was found to be irreversible, and decom-
position to 5a (analogous to retroaldolization) was not ob-
served. Ketone 5a was thus formed exclusively by isomer-
ization of 2a and was detected in small quantities after
short reaction times. The syn/anti ratio was low to moder-
ate, but gratifyingly, the epimerization proceeded at a very
slow rate (i.e. the diastereoisomeric ratio decreased only
from 70:30 to 65:35 over 6 h at 40 °C).
Scheme 9. Reaction of 2a and 26h in [D8]toluene catalyzed by 1a
at 40 °C.
Figure 3. Cross-coupling of 2a and 26h in [D8]toluene catalyzed by
1
1a at 40 °C. Time = 4 min corresponds to the first H NMR spec-
trum recorded. [᭺: 2a; ᭛: 34 (syn + anti); ᮀ:% of syn in 34; Δ: 5a].
From the results obtained and the additional experi-
ments described below, we propose a mechanism via ruthe-
nium alkoxides,[23,24] which is depicted in Scheme 10.
Figure 2. Reaction of 2a and 3a in [D8]toluene catalyzed by 1a at
50 °C (a), 35 °C (b) and 20 °C (c). Time = 4 min corresponds to
the first 1H NMR spectrum recorded. [᭺: 2a; ᭛: 4 (syn + anti);
ᮀ:% of syn in 4; Δ: 5a].
The activation of 1a by KOtBu forms an alkoxide com-
plex [Ru–OtBu] (44). Bäckvall and co-workers have studied
the formation of this intermediate both experimentally and
computationally.[22,24] The reaction of 44 with 2 produced
a new alkoxide complex 45. We studied the mechanism of
these initial steps by NMR spectroscopy (Scheme 11). Thus,
the reaction of KOtBu (1.2 equiv.) with 1a in [D8]toluene
afforded 44,[24] which was smoothly transformed into 45
upon addition of 2a (1 equiv., see Supporting Infor-
mation).[5a] Based on the previous mechanistic investi-
gations by Bäckvall and co-workers, ruthenium alkoxides
(such as 45) undergo CO dissociation to generate the coor-
dination site required for the following step in the catalytic
cycle (i.e. β-hydride elimination).[22] Oxidation of the allylic
alcohol would produce a ruthenium hydride 46 and an en-
one intermediate. Transfer of the hydride to the olefin of
the enone would form an O-bound ruthenium enolate 47a.
Scheme 8. Ketone 5a can be produced by 2a isomerization or by
retroaldolization from 4.
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Synthesis of Functionalized Ketones from Allylic Alcohols
(for 1H NMR spectra, see Supporting Information). Unfor-
tunately, 45 did not evolve into ruthenium enolate interme-
diates (i.e. 47a), instead, 45 and 5a were the only two species
detected in these NMR experiments (Scheme 12).
Scheme 12. Formation of 45 from lithium or sodium allylic alk-
oxides.
When we used 45 (5 mol-%), generated in any of the
above ways (Scheme 12), as the catalyst in the isomerization
of 2a, 5a was formed in quantitative yield. This experiment
supports a mechanism through allylic alkoxide intermedi-
ates 45.
In another attempt to form an O-bound ruthenium enol-
ate species 47a,[25] we reacted 1a with preformed potassium
enolate 52 (Scheme 13). Interestingly, a C-bound ruthenium
enolate 47b was formed instead in about 35% yield. The
remaining sodium enolate 52 was converted into 5a.
Attempts to isolate 47b were unsuccessful due to decompo-
sition. Therefore, the structure of 47b was proposed based
1
on H and 13C NMR spectroscopy (Figure 4) of the reac-
Scheme 10. Plausible catalytic cycle.
tion mixture obtained in this experiment. The structure of
47b agrees well with the data obtained from 2D heteronuc-
lear single quantum coherence (HSQC) experiments (see
We have been unable to identify these last two intermediates
(46 and 47a). Instead, 5a was formed under these experi-
mental conditions.
1
Supporting Information). In the H NMR spectrum of 47b
the CH3 group [Ru–CH–(COPh)CH3] gives a doublet at
1.69 ppm with a coupling constant of 6.5 Hz, and the pro-
ton α to the carbonyl group [Ru–CH–(COPh)CH3] appears
as a quartet at 3.91 ppm (J = 6.5 Hz, Figure 4). In the 13C
NMR spectrum, the CH3 group resonates at 22.3 ppm, and
the CH group directly bound to ruthenium [Ru–CH–
(COPh)CH3] at 27.1 ppm. The latter chemical shift is sim-
ilar to that obtained for other C-bound ruthenium enolates
(e.g. 23.6 ppm)[25c] and clearly differs from that of O-bound
ruthenium enolates (e.g. 76 ppm).[25b] Furthermore, the
ketone carbonyl group appears at 203.8 ppm. In reported
O-bound enolates, such carbon atoms, now part of the
double bond in the enolate form, appear at 169 ppm.[25b]
A
comparison of these chemical shifts with those reported[25]
Scheme 11. Stoichiometric mechanistic investigations.
for O- and C-bound ruthenium enolates is shown in the
In an attempt to characterize ruthenium enolate interme-
diates, we designed a similar experiment to that shown in
Scheme 11, in which the presence of electrophiles, including
alcohols such as tBuOH, was minimized. [Ru–Cl] 1a was
transformed directly into allylic alkoxide complex 45 by re-
action with a lithium or sodium allylic alkoxide salt (50 or
51) generated from 2a and strong bases [nBuLi or sodium
hexamethyldisilazide (NaHMDS), respectively, Scheme 12].
Although the same alkoxide complex 45 was obtained using
either base, the transmetallation of the Li alkoxide to the
Ru center was much slower than that of the Na alkoxide Scheme 13. Stoichiometric mechanistic investigations.
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Supporting Information. Complex 47b did not decompose mation of the unsaturated ketone, impossible for 2-cyclo-
or isomerize to 47a when analyzed by NMR spectroscopy hexenone, is required. From the s-cis conformation of 46,
at temperatures from –50 to +50 °C. In addition, 47b cata- 1,4-hydride addition would yield (Z)-enolate 47a.
lyzed neither the isomerization of 2a nor the tandem isom-
erization/aldolization, which indicates that 47b is not a cata-
lytically active species. A plausible explanation is that the
catalytically active species requires the dissociation of one
of the CO ligands,[22] which may be difficult from 47b. Com-
plex 47b may have been formed from the corresponding O-
bound ruthenium enolate, a process well described and
studied for related enolate complexes.[25]
Scheme 15. Crossover experiment.
Scheme 16. Enone reduction step.
Figure 4. C-Bound ruthenium enolate 47b.
To obtain insights into the elusive 1,4-addition step, ad-
ditional experiments with deuterated substrates were car-
ried out. The coupling between deuterated allylic alcohol
[D1]-2a and 3a afforded monodeuterated [D1]-4, with the
deuterium label incorporated at the methyl group
(Scheme 14). This deuterium distribution agrees with the
proposed mechanism shown in Scheme 10.
Scheme 17. Unsuccessful coupling of 2-cyclohexen-1-ol with 3a.
Scheme 14. Coupling of a deuterium-labeled allylic alcohol.
To verify whether the enone intermediate stays coordi-
The next step in the reaction mechanism is the C–C bond
nated to the ruthenium center as in Ru hydride 46, we per- formation. Preferential formation of the syn-aldol from (Z)-
formed a crossover experiment (Scheme 15), namely, the enolate 47a and 3 can be explained by a Zimmerman–
Ru-catalyzed reaction of 2b and 3a in the presence of Traxler six-membered transition state.[26] We propose that
phenyl vinyl ketone. Aldol 13 was formed as the sole prod- under the applied reaction conditions, the C–C bond is
uct, which indicates that the enone produced within the co- formed from a ruthenium intermediate in which both alde-
ordination sphere of the metal is reduced before it can dif- hyde and enolate are bound to the metal center, rather than
fuse into the reaction mixture. Further support for the co- from a free enol without participation of the ruthenium.[5m]
ordination of the α,β-unsaturated ketone to the Ru hydride This is supported by several arguments. First, it is highly
comes from the fact that the aldehydes 3 used as electro- unlikely that the free enol would react exclusively with the
philes are not reduced to the corresponding alcohols during aldehyde and would not, at least partially, tautomerize to
the reaction. Thus, we propose that the 1,4-hydride addition the corresponding ketone 5a (Scheme 8). Secondly, we ob-
occurs intramolecularly via an s-cis conformation of the en- served that the retroaldol reaction occurs only in the pres-
one intermediate (Scheme 16). This process would result in ence of the ruthenium catalyst. When 4 is subjected to the
a stereospecific (Z)-enolate formation. The support for this reaction conditions in the absence of 1a, KOtBu, or 44, de-
hypothesis is that, in a separate experiment, 2-cyclohexen- composition of 4 does not occur. Thus, the retroaldol pro-
1-ol failed to isomerize to cyclohexanone or to yield any cess (C–C bond breaking) is catalyzed by the Ru complex,
aldol in the presence of 3a (Scheme 17). Only traces of 2- which was confirmed by the reaction of 4 with 44 (Support-
cyclohexenone and p-chlorobenzyl alcohol were detected. ing Information, pages S10 and S13). According to the mi-
Thus, for this particular allylic alcohol, β-hydride elimi- croscopic reversibility principle,[27] the C–C bond formation
nation occurred, and the following 1,4-hydride addition should be also mediated by the ruthenium complex. Finally,
step did not take place, which suggests that an s-cis confor- it is reasonable to assume that the anti-aldol is mainly pro-
1524
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2012, 1517–1530

Synthesis of Functionalized Ketones from Allylic Alcohols
ane, 34.9 mmol) was added to a 250 mL 2-necked flask that con-
tained dry THF (30 mL) at –66 °C under a nitrogen atmosphere.
1-Bromonaphthalene (3.7 mL, 26.8 mmol) was added dropwise at
–66 °C. After the addition was finished, the clear yellowish solution
was stirred for 1 h at –66 °C and then warmed to 0 °C. A solution
of 2,3,4,5-tetraphenylcyclopentadienone (5.14 g, 13.4 mmol) in dry
THF (80 mL) was added slowly to the reaction mixture at 0 °C.
After stirring overnight at ambient temperature, the mixture was
quenched with dilute HCl (aq.) and water and extracted with tolu-
ene. The combined organic phases were dried with Na2CO3, fil-
duced by Ru-catalyzed epimerization of the syn-aldol (vide
supra, Figure 2 shows how the syn/anti ratio diminishes as
the reaction proceeds). It is known that 1a catalyzes a fast
racemization of sec-alcohols, which proceeds by consecutive
β-hydride elimination and 1,2-hydride addition.[24] Epi-
merization of aldolate syn-49 would occur before proton-
ation by ligand exchange with allylic alcohol. This process
would produce aldolate anti-49, which would lead to the
formation of anti-aldol. Indeed, when syn-49 was prepared
from syn-4, epimerization into anti-49 occurred within min- tered, and the solvents evaporated. Purification by column
chromatography (SiO2, pentane/EtOAc, 15:1) afforded 1-(1-naph-
thyl)-2,3,4,5-tetraphenylcyclopentadienol (yellow solid, 6.1 g,
89%): H NMR (400 MHz, CDCl3): δ = 2.68 (s, 1 H), 6.8–7.2 (m,
utes (characterization of syn- and anti-49 and their equili-
bration is shown in the Supporting Information).
1
20 H), 7.40–7.50 (m, 3 H), 7.73 (d, J = 8.20 Hz, 1 H), 7.73 (dd, J
= 8.6, 1.6 Hz, 1 H), 8.12 (dd, J = 7.4, 1.2 Hz, 1 H), 8.64 (dd, J =
8.5, 1 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 89.8, 124.3,
125.3, 125.4, 125.9, 126.1, 127.0, 127.1, 127.5, 127.9, 128.7, 128.8,
129.4, 129.7, 129.8, 133.7, 133.8, 135.1, 135.2, 143.1, 148.7 ppm.
Conclusions
We have expanded the scope of the reaction of allylic
alcohols with aldehydes catalyzed by 1a. Both aromatic and
aliphatic aldehydes afforded β-hydroxy ketones in excellent
yields. This tandem isomerization/C–C bond formation
process has been extended to the use of imines as electro-
philes as well, which resulted in the formation of β-amino
ketones from allylic alcohols. The higher efficiency of the
reaction in terms of yields at milder reaction conditions is
explained by the suppression of a retroaldolization reaction.
Investigations of the tandem isomerization/aldol coupling
supported a mechanism through ruthenium allylic alkoxide
intermediates, which undergo β-hydride elimination to pro-
duce ruthenium hydride species and the corresponding en-
ones. Consecutive 1,4-hydride addition to the enones in an
(S)-cis conformation produces ruthenium (Z)-enolates. A
Zimmerman–Traxler transition state in the following C–C
bond formation step would form a ruthenium syn-aldolate,
which agrees with the high diastereoselectivity obtained at
short reaction times (syn/anti = 94:6). A C-bound ruthe-
nium enolate has been prepared and characterized by NMR
and was found to be catalytically inactive.
Compound 54 (1.8 g, 3.5 mmol) was dissolved in glacial acetic acid
(45 mL) at 100 °C, and HCl (1.8 mL, 12 m solution in H2O,
21.6 mmol) was added dropwise over 5 min. The color of the solu-
tion changed from yellow to light orange. The mixture was heated
to reflux for 1.5 h. H2SO4 (0.2 mL, 18.4 m, 3.7 mmol, 1.05 equiv.)
was added dropwise, and the reaction mixture was heated to reflux
for an additional 1.5 h. The reaction mixture was allowed to cool
to 100 °C, and zinc dust was added in two portions (485 mg,
7.4 mmol; after two hours of reflux, additional Zn was added:
250 mg, 3.6 mmol). HCl (11 m, 0.5 mL) was added, and the mixture
was heated to reflux for another 2 h. The reaction was neutralized
with NaOH and extracted with toluene (60 mL). Drying over
MgSO4 and evaporation afforded a brown viscous oil. The mixture
was purified by gradient flash column chromatography (SiO2) with
pentane/EtOAc, 30:1 to 10:1 as eluent system. Tetraphenyl-(1-
naphthyl)cyclopentadiene (55) was obtained as a mixture of iso-
1
mers (800 mg, 1.6 mmol, 46.0%). H NMR (400 MHz, CDCl3; se-
lected peaks): δ = 5.20 (s), 5.37 (s), 5.41 (s), 8.21–6.82 ppm. A sus-
pension of 55 (1.092 g, 2.2 mmol) and Ru3(CO)12 (478 mg,
0.74 mmol) in a mixture of decane (8 mL) and toluene (4 mL) was
heated at 160 °C in a 35 mL sealed tube for 3 d. After cooling the
mixture to room temperature, CHCl3 (1 mL) was added and the
mixture was heated at 160 ᭺C for 1 h. After cooling to room tem-
perature, pentane was added and the resulting yellow powder was
collected by filtration. After purification by column chromatog-
raphy (SiO2, pentane/CH2Cl2, 3:1), 1e was obtained as a yellow
Experimental Section
General: All reactions were carried out under dry argon atmo-
sphere in flame-dried glassware. Reagents were of analytical grade,
obtained from commercial suppliers, and used without further pu-
rification. Compounds 26a–o,[28] 1f,[9] 1g,[10] 1h,[11] 1i,[12] 2a,[29]
2b,[30] 2c,[31] 2e,[32] 2f,[31] [LnRu–OtBu] 44,[6a] and 45[6a] were pre-
pared as described previously. Anhydrous THF and toluene were
obtained using a VAC solvent purifier system. Flash chromatog-
raphy was carried out with Davisil silica gel 60 (35–70 μm). 1H and
13C NMR spectra were recorded at 400 and 100 MHz, respectively,
with a Bruker Avance spectrometer. Chemical shifts (δ) are re-
ported in ppm using the residual solvent peak in CDCl3 (δH = 7.26
1
solid (908 mg, 60%). H NMR (400 MHz, CDCl3): δ = 7.93–6.80
(m) ppm. 13CNMR (100 MHz, CDCl3): δ = 101.1, 103.6, 113.8,
124.9, 125.7, 125.8, 126.3, 127.3, 127.6, 128.0, 128.4, 128.4, 128.5,
129.0, 129.4, 129.9, 131.1, 132.2, 132.3, 133.1, 133.8, 196.8 ppm.
General Procedure for the Synthesis of β-Hydroxy and β-Amino
Ketones: KOtBu (0.5 m in THF, 0.024 mmol, 6–7 mol-%) was added
to a mixture of 1a (13 mg, 0.020 mmol, 5 mol-%), powdered ms
(4 Å) (20 mg) or Na2CO3 (42 mg, 0.4 mmol) in degassed toluene
(1 mL) under a nitrogen atmosphere (MS 4 Å, were added instead
of Na2CO3 in order to suppress self-aldolization of aliphatic alde-
hydes 3o and 3p, and was also used for all Mannich-type reactions
to suppress hydrolysis of imines 26). The mixture was stirred for
3 min before a solution of 2 (0.4 mmol) and 3 (0.6 mmol) or 26
(0.44 mmol) in degassed toluene (1 mL) was added by syringe. The
mixture was heated at the appropriate temperature (Table 2 and
Table 4). The products were isolated by column chromatography
(SiO2, pentane/AcOEt systems) usually as an inseparable mixture
of syn and anti diastereomers. If necessary, further purification was
and δC = 77.00 ppm) or [D8]toluene (δH = 2.09 and δC
=
20.40 ppm) as internal standards, and coupling constants (J) are
given in Hz; quint stands for quintuplet, and app. stands for appar-
ent. HRMS were recorded with a Bruker microTOF ESI-TOF
mass spectrometer. MS 4 Å powder was dried at 400 °C overnight
before use.
Ruthenium Complex 1e: Complex 1e was prepared in three steps
from 1-bromonaphthalene. tBuLi (21 mL, 1.7 m solution in pent-
Eur. J. Inorg. Chem. 2012, 1517–1530
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1525

B. Martín-Matute et al.
FULL PAPER
performed by preparative HPLC (RI detector, M2-Preparative col-
umn, 250ϫ20 mm, 100 SIL, 5 μm).
(Z)-4-Bromo-3-hydroxy-2-methyl-1,5-diphenylpent-4-en-1-one (18):
syn-18/anti-18 = 87:13 (109 mg, 79%), colorless oil. 1H NMR
(400 MHz, CDCl3) syn: δ = 8.08–8.00 (m, 2 H), 7.68–7.48 (m, 5
H), 7.42–7.26 (m, 4 H), 4.85 (br. s, 1 H), 4.18 (dq, J = 3.9, 7.3 Hz,
1 H), 3.66 (br. s, 1 H), 1.32 (d, J = 7.3 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3) syn: δ = 204.8, 135.7, 135.3, 133.8, 129.1, 129.0,
128.9, 128.6, 128.1, 128.0, 125.0, 76.5, 42.8, 11.2 ppm. 1H NMR
(400 MHz, CDCl3) anti: δ = 8.08–8.02 (m, 2 H), 7.66–7.57 (m, 3
H), 7.56–7.49 (m, 2 H), 7.42–7.31 (m, 3 H), 7.19 (br. s, 1 H), 4.65
(t, J = Hz, 1 H 6.9), 4.15 (app. quint, J = 7.3 Hz, 1 H), 3.29 (d, J
= Hz, 1 H 6.6), 1.28 (d, J = 7.3 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3) anti: δ = 204.3, 136.7, 134.9, 133.6, 130.3, 129.2,
128.8, 128.6, 128.3, 128.2, 127.6, 80.0, 43.9, 15.7 ppm. HRMS
(ESI) syn, anti: calcd. for C18H17BrNaO2 [M]+ 367.0304; found
367.0322.
3-Hydroxy-2-methyl-1-phenyl-3-(pyridin-2-yl)propan-1-one
(11):
syn-11/anti-11 = 83:17 (88 mg, 91%), colorless oil. 1H NMR
(400 MHz, CDCl3): δ = 8.68–8.64 (m, 1 H syn + 1 H anti), 8.58–
8.53 (m, 1 H syn + 1 H anti), 7.99–7.95 (m, 2 H syn, 2 H anti),
7.83–7.78 (m, 1 H syn, 1 H anti), 7.67–7.59 (m, 1 H syn, 1 H anti),
7.55–7.48 (m, 2 H syn, 2 H anti), 7.35–730 (m, 1 H syn, 1 H anti),
5.33 (syn) (d, J = 2.8 Hz, 1 H), 5.07 (anti) (d, J = 8.3 Hz, 1 H),
3.94 (syn) (br. s, 1 H), 3.86 (anti) (app. quint, J = 7.6 Hz, 1 H),
3.71 (syn) (dq, J = 3.0, 7.3 Hz, 1 H), 3.40 (anti) (br. s, 1 H), 1.22
(syn) (d, J = 7.3 Hz, 3 H), 1.16 (anti) (d, J = 7.3 Hz, 3 H) ppm.
13C NMR (100 MHz, CDCl3) syn, anti: δ = 205.1, 204.4, 149.1,
148.6, 148.5, 147.8, 138.1, 137.7, 136.6, 135.5, 134.5, 134.2, 133.8,
133.5, 128.9, 128.8, 128.52, 128.51, 123.6, 123.3, 74.4, 71.3, 47.9,
47.0, 15.6, 11.5 ppm. HRMS (ESI): calcd. for C15H15NNaO2
[M]+ 264.0995; found 264.0989.
(E)-3-Hydroxy-2,4-dimethyl-1,5-diphenylpent-4-en-1-one
(19):[33]
syn-19/anti-19 = 50:50 (54 mg, 48%), colorless oil. 1H NMR
(400 MHz, CDCl3) syn: δ = 8.02–7.98 (m, 2 H), 7.66–7.60 (m, 1
H), 7.56–7.51 (m, 2 H), 7.37–7.20 (m, 5 H), 6.73 (br. s, 1 H), 4.63
(br. d, J = 2.6 Hz, 1 H), 3.79 (dq, J = 3.4, 7.2 Hz, 1 H), 3.46 (br.
s, 1 H), 1.90 (d, J = 1.4 Hz, 3 H), 1.31 (d, J = 7.2 Hz, 3 H) ppm.
13C NMR (100 MHz, CDCl3) syn: δ = 205.4, 137.7, 136.3, 136.0,
133.5, 129.0, 128.8, 128.5, 128.1, 126.39, 126.36, 75.7, 42.9, 15.4,
3-(4-Chlorophenyl)-3-hydroxy-1-(4-methoxyphenyl)-2-methylpropan-
1-one (13): syn-13/anti-13 = 79:21 (96 mg, 79%), colorless oil. 1H
NMR (400 MHz, CDCl3): δ = 7.96–7.90 (m, 2 H syn, 2 H anti),
7.38–7.29 (m, 4 H syn, 4 H anti), 6.98–6.89 (m, 2 H syn, 2 H anti),
5.20 (syn) (dd, J = 1.9, 2.7 Hz, 1 H), 4.94 (anti) (dd, J = 5.3, 7.5 Hz,
1 H), 3.99 (syn) (d, J = 1.9 Hz, 1 H), 3.88 (syn) (s, 3 H), 3.87 (anti)
(s, 3 H), 3.73 (anti) (app. quint, J = 7.4 Hz, 1 H), 3.58 (syn) (dq, J
= 2.7, 7.2 Hz, 1 H), 3.33 (anti) (d, J = 5.3 Hz, 1 H), 1.14 (syn) (d,
J = 7.3 Hz, 3 H), 1.07 (anti) (d, J = 7.5 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3) syn, anti: δ = 204.3, 203.2, 164.1, 163.0, 141.0,
140.4, 133.4, 132.9, 130.9, 130.8, 129.4, 128.6, 128.4, 128.3, 128.0,
127.5, 114.0, 113.9, 77.2, 76.1, 72.5, 55.6, 47.3, 46.3, 16.0, 11.2 ppm.
HRMS (ESI): calcd. for C17H17ClNaO3 [M]+ 327.0758; found
327.0754.
1
11.3 ppm. H NMR (400 MHz, CDCl3) anti: δ = 8.07–8.00 (m, 2
H), 7.65–7.58 (m, 1 H), 7.56–7.48 (m, 2 H), 7.40–7.22 (m, 5 H),
6.60 (br. s, 1 H), 4.56 (dd, J = 4.3, 8.4 Hz, 1 H), 3.86 (dq, J = 7.2,
8.4 Hz, 1 H), 2.67 (d, J = 4.3 Hz, 1 H), 1.97 (d, J = 1.3 Hz, 3 H),
1.21 (d, J = 7.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3) anti:
δ = 204.9, 137.6, 137.2, 137.1, 133.3, 129.0, 128.7, 128.5, 128.4,
128.1, 126.7, 80.6, 43.9, 15.6, 13.1 ppm. HRMS (ESI) syn, anti:
calcd. for C19H20NaO2 [M]+ 303.1356; found 303.1360.
3-Hydroxy-2-methyl-1-phenylpent-4-en-1-one (20):[34] syn-20/anti-20
= 56:44 (137 mg, 72%), colorless oil. 1H NMR (400 MHz, CDCl3):
δ = 8.05–7.99 (m, 2 H syn, 2 H anti), 7.68–7.59 (m, 1 H syn, 1 H
anti), 7.58–7.49 (m, 2 H syn, 2 H anti), 5.99 (anti) (ddd, J = 6.5,
10.3, 17.3 Hz, 1 H), 5.94 (syn) (ddd, J = 5.1, 10.4, 17.2 Hz, 1 H),
5.44 (syn) (dt, J = 1.6, 17.3 Hz, 1 H), 5.40 (anti) (dt, J = 1.4,
17.3 Hz, 1 H), 5.27 (syn) (dt, J = 1.6, 10.4 Hz, 1 H), 5.26 (anti) (dt,
J = 1.4 Hz, 1 H, 10.3), 4.68 (syn) (m, 1 H), 4.47 (anti) (m, 1 H),
3.66 (anti) (app. quint, J = 7.2 Hz, 1 H), 3.60 (syn) (dq, J = 3.4,
7.2 Hz, 1 H), 3.19 (syn) (d, J = 2.7 Hz, 1 H), 2.89 (anti) (d, J =
5.9 Hz, 1 H), 1.32 (syn) (d, J = 7.2 Hz, 3 H), 1.30 (anti) (d, J =
7.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3) syn, anti: δ =
205.2, 204.9, 138.5, 137.9, 136.6, 135.9, 133.5, 133.4, 128.8, 128.7,
128.5, 128.4, 116.8, 116.0, 75.4, 72.3, 45.0, 15.3, 11.6 ppm. HRMS
(ESI): calcd. for C12H14NaO2 [M]+ 213.0886; found 213.0886.
1,3-Bis(4-chlorophenyl)-3-hydroxy-2-methylpropan-1-one (14): syn-
14/anti-14 = 75:25 (93 mg, 75%), colorless oil. 1H NMR (400 MHz,
CDCl3): δ = 7.95–7.91 (m, 2 H anti), 7.91–7.86 (m, 2 H syn), 7.51–
7.45 (m, 2 H syn, 2 H anti), 7.38–7.34 (m, 4 H syn, 4 H anti), 5.23
(syn) (dd, J = 2.1, 3.2 Hz, 1 H), 4.98 (anti) (dd, J = 4.7, 8.1 Hz, 1
H), 3.74 (anti) (app. quint, J = 7.3 Hz, 1 H), 3.61 (syn) (d, J =
2.1 Hz, 1 H), 3.61 (syn) (dq, J = 3.2, 7.2 Hz, 1 H), 2.93 (anti) (d, J
= 4.7 Hz, 1 H), 1.19 (syn) (d, J = 7.2 Hz, 3 H), 1.08 (anti) (d, J =
7.3 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3) syn, anti: δ =
204.2, 203.4, 140.6, 140.30, 140.26, 140.0, 135.0, 133.9, 133.8,
133.2, 133.0, 129.2, 129.1, 128.7, 128.5, 128.1, 127.8, 127.5, 76.1,
72.6, 48.0, 47.1, 15.6, 11.4 ppm. HRMS (ESI): calcd. for
C16H14Cl2NaO2 [M]+ 331.0263; found 331.0251.
(E)-3-Hydroxy-2-methyl-1,5-diphenylpent-4-en-1-one (17):[33] syn-
17/anti-17 = 54:46 (80 mg, 75%), colorless oil. 1H NMR (400 MHz,
CDCl3) syn: δ = 8.02–7.98 (m, 2 H), 7.66–7.59 (m, 1 H), 7.56–7.49
(m, 2 H), 7.43–7.39 (m, 2 H), 7.37–7.30 (m, 2 H), 7.29–7.24 (m, 1
H), 6.75 (dd, J = 1.5, 16.0 Hz, 1 H), 6.27 (dd, J = 5.8, 16.0 Hz, 1
H), 4.83 (a t, J = 3.5 Hz, 1 H), 3.67 (dq, J = 3.5, 7.3 Hz, 1 H), 3.34
(br. s, 1 H), 1.34 (d, J = 7.3 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3) syn: δ = 205.3, 136.7, 135.9, 133.6, 131.1, 129.2, 128.8,
128.6, 128.5, 127.6, 126.5, 72.2, 45.4, 11.8 ppm. 1H NMR
(400 MHz, CDCl3) anti: δ = 8.05–7.98 (m, 2 H), 7.64–7.58 (m, 1
H), 7.55–7.47 (m, 2 H), 7.43–7.37 (m, 2 H), 7.37–7.30 (m, 2 H),
7.28–7.23 (m, 1 H), 6.70 (d, J = 15.9 Hz, 1 H), 6.30 (dd, J = 7.2,
15.9 Hz, 1 H), 4.62 (m, 1 H), 3.72 (app. quint, J = 7.2 Hz, 1 H),
2.92 (d, J = 7.2 Hz, 1 H), 1.29 (d, J = 7.2 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3) anti: δ = 204.8, 136.7, 136.5, 133.4, 132.1, 129.7,
128.7, 128.6, 128.5, 127.8, 126.6, 75.3, 46.4, 15.4 ppm. HRMS
(E)-3-Hydroxy-2-methyl-1-phenylhex-4-en-1-one (21):[35] syn-21/
anti-21 = 48:52 (70 mg, 86%), colorless oil. 1H NMR (400 MHz,
CDCl3): δ = 8.03–7.94 (m, 2 H syn, 2 H anti), 7.65–7.57 (m, 1 H
syn, 1 H anti), 7.54–7.46 (m, 2 H syn, 2 H anti), 5.85–5.73 (m, 1 H
syn, 1 H anti), 5.61–5.52 (m, 1 H syn, 1 H anti), 4.55 (syn) (br. s, 1
H), 4.38 (anti) (m, 1 H), 3.59 (anti) (m, 1 H), 3.55 (syn) (m, 1 H),
2.99 (syn) (d, J = 2.5 Hz, 1 H), 2.68 (anti) (d, J = 5.0 Hz, 1 H),
1.76–1.71 (m, 3 H syn, 3 H anti), 1.29 (syn) (d, J = 7.3 Hz, 3 H),
1.21 (anti) (d, J = 7.3 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3)
syn, anti: δ = 205.3, 205.00, 136.8, 136.1, 133.4, 133.3, 131.5, 130.8,
128.9, 128.74, 128.67, 128.5, 128.4, 127.9, 75.4, 72.5, 46.3, 45.5,
17.77, 17.78, 15.4, 11.8 ppm. HRMS (ESI): calcd. for C13H16NaO2
[M]+ 227.1043; found 227.1046.
3-Hydroxy-2,5-dimethyl-1-phenylhex-4-en-1-one (22): syn-22/anti-22
1
(ESI) syn, anti: calcd. for C18H18NaO2 [M]+ 289.1199; found = 77:23 (67 mg, 77%), colorless oil. H NMR (400 MHz, CDCl3):
289.1208.
δ = 8.00–7.91 (m, 2 H syn, 2 H anti), 7.60–7.55 (m, 1 H syn, 1 H
1526
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2012, 1517–1530

Synthesis of Functionalized Ketones from Allylic Alcohols
anti), 7.51–7.50 (m, 2 H syn, 2 H anti), 5.29 (syn) (m, 1 H), 5.26
(anti) (m, 1 H), 4.76 (syn) (dd, J = 4.3, 8.8 Hz, 1 H), 4.72 (anti) (t,
J = 8.8 Hz, 1 H), 3.57 (anti) (app. quint, J = 7.4 Hz, 1 H), 3.55
(syn) (dq, J = 4.4, 7.1 Hz, 1 H), 2.73 (syn) (br. s, 1 H), 2.49 (anti)
(br. s, 1 H), 1.79 (anti) (d, J = 1.3 Hz, 3 H), 1.76 (anti) (d, J =
1.3 Hz, 3 H), 1.72 (syn) (d, J = 1.4 Hz, 3 H), 1.71 (syn) (d, J =
1.4 Hz, 3 H), 1.33 (syn) (d, J = 7.1 Hz, 3 H), 1.17 (anti) (d, J =
7.4 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3) syn, anti: δ =
N-[1-(4-Fluorophenyl)-2-methyl-3-oxo-3-phenylpropyl]-4-methyl-
benzenesulfonamide (34): syn-34/anti-34 = 62:38 (128 mg, 78%),
white powder. 1H NMR (400 MHz, CDCl3) syn: δ = 7.75–7.68 (m,
2 H), 7.60–7.49 (m, 3 H), 7.42–7.34 (m, 2 H), 7.14–7.03 (m, 4 H),
6.81–6.71 (m, 2 H), 5.83 (d, J = 8.0 Hz, 1 H), 4.64 (t, J = 8.1 Hz,
1 H), 3.87 (app. quint, J = 7.1 Hz, 1 H), 2.34 (s, 3 H), 1.29 (d, J =
7.1 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3) syn: δ = 201.6,
161.7 [d, 1J(13C–19F) = 246.2 Hz], 143.3, 136.9, 135.7 [d, 4J(13C–
205.13, 205.07, 137.0, 136.9, 136.4, 136.1, 133.3, 133.2, 128.74, 19F) = 3.2 Hz], 135.4, 133.4, 129.3, 128.8 [d, 3J(13C–19F) = 8.1 Hz],
128.68, 128.49, 128.46, 125.5, 125.0, 70.8, 69.1, 47.1, 45.9, 26.0,
25.9, 18.6, 18.5, 15.1, 12.3 ppm. HRMS (ESI): calcd. for
C14H18NaO2 [M]+ 241.1199; found 241.1197.
128.6, 128.1, 127.2, 115.1 [d, 2J(13C–19F) = 21.5 Hz], 59.1, 46.7,
21.4, 14.7 ppm. HRMS (ESI) syn: calcd. for C23H22FNNaO3S
[M]+ 434.1197; found 434.1217. 1H NMR (400 MHz, CDCl3) anti:
δ = 7.73–7.68 (m, 2 H), 7.57–7.49 (m, 3 H), 7.44–7.36 (m, 2 H),
7.14–7.08 (m, 2 H), 7.07–7.00 (m, 4 H), 6.81–6.72 (m, 2 H), 6.48
(d, J = 8.7 Hz, 1 H), 4.72 (dd, J = 4.8, 8.7 Hz, 1 H), 3.88 (dq, J =
4.8, 7.2 Hz, 1 H), 2.33 (s, 3 H), 1.31 (d, J = 7.3 Hz, 1 H) ppm. 13C
3-Hydroxy-2,5-dimethyl-1-phenylhexan-1-one (23): syn-23/anti-23 =
92:8 (81 mg, 92%), colorless oil. 1H NMR (400 MHz, CDCl3): δ =
8.00–7.94 (m, 2 H syn, 2 H anti), 7.65–7.59 (m, 1 H syn, 1 H anti),
7.56–7.48 (m, 2 H syn, 2 H anti), 4.16 (syn) (ddd, J = 2.9, 3.9,
9.4 Hz, 1 H), 3.96 (anti) (ddd, J = 3.0, 5.9, 10.0 Hz, 1 H), 3.53
(anti) (dq, J = 5.9, 7.2 Hz, 1 H), 3.44 (syn) (dq, J = 2.9, 7.3 Hz, 1
H), 3.16–2.55 (br. s, 1 H syn, 1 H anti), 1.97–1.78 (m, 1 H syn, 1
H anti), 1.60 (syn) (ddd, J = 5.3, 9.4, 13.7 Hz, 1 H), 1.49 (anti)
(ddd, J = 4.4, 10, 13.7 Hz, 1 H), 1.33–1.26 (anti) (m, 1 H), 1.29
(anti) (d, J = 7.2 Hz, 3 H), 1.28 (syn) (d, J = 7.3 Hz, 3 H), 1.19
(syn) (ddd, J = 3.9, 8.6, 13.7 Hz, 1 H), 0.97 (syn) (d, J = 3.1 Hz, 3
H), ca. 0.96 (anti) (d, 3 H, overlaps with 0.97 syn), 0.95 (syn) (d, J
= 3.1 Hz, 3 H), 0.93 (anti) (d, J = 6.5 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3) syn, anti: δ = 206.1, 206.0, 136.7, 136.0, 133.5,
133.4, 128.82, 128.77, 128.5, 128.4, 72.3, 69.2, 46.3, 45.0, 44.2, 43.5,
24.7, 24.6, 23.8, 23.5, 22.0, 21.7, 15.6, 11.2 ppm. HRMS (ESI):
calcd. for C14H20NaO2 [M]+ 243.1356; found 243.1347.
1
NMR (100 MHz, CDCl3) anti: δ = 203.9, 162.6 [d, J(13C–19F) =
248.0 Hz], 142.9, 138.0, 136.1, 135.4 [d, 4J(13C–19F) = 3.1 Hz],
133.7, 129.2, 128.7, 128.3 [d, 3J(13C–19F) = 8.1 Hz], 128.2, 126.9,
115.0 [d, 2J(13C–19F) = 21.5 Hz], 60.1, 46.0, 21.4, 16.8 ppm. HRMS
(ESI) anti: calcd. for C23H22FNNaO3S: 434.1197; found 434.1220.
N-[1-(4-Bromophenyl)-2-methyl-3-oxo-3-phenylpropyl]-4-methyl-
benzenesulfonamide (35): syn-35/anti-35 = 73:27 (147 mg, 78%),
white powder. 1H NMR (400 MHz, CDCl3) syn: δ = 7.76–7.69 (m,
2 H), 7.55–7.49 (m, 3 H), 7.43–7.37 (m, 2 H), 7.25–7.19 (m, 2 H),
7.10–7.05 (m, 2 H), 7.03–6.97 (m, 2 H), 5.65 (d, J = 7.5 Hz, 1 H),
4.60 (t, J = 7.5 Hz, 1 H), 3.85 (app. quint, J = 7.4 Hz, 1 H), 2.36
(s, 3 H), 1.26 (d, J = 7.4 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3) syn: δ = 201.4, 143.4, 138.5, 136.7, 135.6, 133.5, 131.3,
129.4, 128.9, 128.7, 128.1, 127.2, 121.4, 59.1, 46.3, 21.5, 14.3 ppm.
HRMS (ESI) syn: calcd. for C23H22BrNNaO3S [M]+ 494.0396;
4-Ethyl-3-hydroxy-2-methyl-1-phenylhexan-1-one (24): syn-24/anti-
24 = 89:11 (71 mg, 76%), colorless oil, only syn was isolated. 1H
NMR (400 MHz, CDCl3) (syn): δ = 8.00–7.95 (m, 2 H), 7.65–7.59
(m, 1 H), 7.54–7.48 (m, 2 H), 3.92 (dt, J = 3.3, 7.3 Hz, 1 H), 3.70
(dq, J = 3.3, 7.1 Hz, 1 H), 2.98 (d, J = 3.3 Hz, 1 H), 1.76–1.62 (m,
1 H), 1.55–1.33 (m, 4 H), 1.28 (d, J = 7.1 Hz, 3 H), 0.94 (t, J =
7.3 Hz, 3 H), 0.87 (t, J = 7.3 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3, syn): δ = 206.0, 136.1, 133.4, 128.8, 128.4, 72.6, 42.5, 41.9,
21.3, 20.5, 11.4, 10.7, 10.5 ppm. HRMS (ESI): calcd. for
C15H22NaO2 [M]+ 257.1512; found 257.1519.
1
found 494.0381. H NMR (400 MHz, CDCl3) anti: δ = 7.75–7.69
(m, 2 H), 7.58–7.50 (m, 3 H), 7.44–7.37 (m, 2 H), 7.22–7.17 (m, 2
H), 7.15–7.08 (m, 2 H), 6.97–6.91 (m, 2 H), 6.51 (d, J = 8.8 Hz, 1
H), 4.68 (dd, J = 4.6, 8.8 Hz, 1 H), 3.87 (dq, J = 4.9, 7.3 Hz, 1 H),
2.38 (s, 3 H), 1.33 (d, J = 7.3 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3) anti: δ = 203.7, 143.1, 138.6, 137.9, 136.0, 133.8, 131.3,
129.2, 128.8, 128.5, 128.2, 126.9, 121.1, 60.2, 45.8, 21.4, 16.9 ppm.
HRMS (ESI) anti: calcd. for C23H22BrNNaO3S [M]+ 494.0396;
found 494.0422.
2-Methyl-1-phenylpentane-1,3-dione (25):[36] 25 could not be sepa-
1
N-[1-(3-Bromophenyl)-2-methyl-3-oxo-3-phenylpropyl]-4-methyl-
benzenesulfonamide (36): syn-36/anti-36 = 63:37 (156 mg, 83%),
white powder. 1H NMR (400 MHz, CDCl3) syn: δ = 7.77–7.72 (m,
2 H), 7.59–7.49 (m, 3 H), 7.45–7.39 (m, 2 H), 7.27–7.22 (m, 1 H),
7.15–7.08 (m, 4 H), 7.07–7.01 (m, 1 H), 5.26 (d, J = 7.2 Hz, 1 H),
4.58 (t, J = 7.2 Hz, 1 H), 3.85 (app. quint, J = 7.2 Hz, 1 H), 2.36
(s, 3 H), 1.27 (d, J = 7.2 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3) syn: δ = 201.3, 143.5, 141.6, 136.4, 135.5, 133.5, 130.6,
130.5, 129.9, 129.4, 128.7, 128.2, 127.2, 125.5, 122.4, 58.9, 46.2,
21.5, 14.0 ppm. HRMS (ESI) syn: calcd. for C23H22BrNNaO3S
[M]+ 494.0396; found 494.0379. 1H NMR (400 MHz, CDCl3) anti:
δ = 7.78–7.70 (m, 2 H), 7.58–7.50 (m, 3 H), 7.44–7.37 (m, 2 H),
7.21–7.14 (m, 1 H), 7.13–7.06 (m, 3 H), 7.05–7.00 (m, 1 H), 7.00–
6.93 (m, 1 H), 6.49 (d, J = 9.0 Hz, 1 H), 4.69 (dd, J = 4.7, 9.0 Hz,
1 H), 3.88 (dq, J = 4.7, 7.2 Hz, 1 H), 2.36 (s, 3 H), 1.33 (d, J =
7.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3) anti: δ = 203.5,
143.1, 141.7, 137.8, 136.0, 133.7, 130.3, 129.9, 129.8, 129.3, 128.7,
128.2, 126.8, 125.4, 122.4, 60.2, 45.8, 21.4, 16.8 ppm. HRMS (ESI):
calcd. for C23H22BrNNaO3S [M]+ 494.0396; found 494.0383.
rated from traces of 5a and 1a. H NMR (400 MHz, CDCl3): δ =
8.02–796 (m, 2 H), 7.65–7.55 (m, 1 H), 7.54–7.46 (m, 2 H), 4.53 (q,
J = 4.5 Hz, 1 H), 2.50 (m, 2 H), 1.48 (d, J = 7.0 Hz, 3 H), 1.04 (t,
J = 7.4 Hz, 3 H) ppm. HRMS (ESI): calcd. for C12H14NaO2 [M]+
213.0886; found 213.0878.
4-Methyl-N-(2-methyl-3-oxo-1,3-diphenylpropyl)benzenesulfonamide
(31):[37] syn-31/anti-31 = 71:29 (126 mg, 80%), white powder. 1H
NMR (400 MHz, CDCl3) syn: δ = 7.77–7.69 (m, 2 H), 7.57–7.49
(m, 3 H), 7.42–7.36 (m, 2 H), 7.16–7.04 (m, 7 H), 5.41 (d, J =
7.4 Hz, 1 H), 4.64 (t, J = 7.4 Hz, 1 H), 3.89 (app. quint, J = 7.3 Hz,
1 H), 2.33 (s, 3 H), 1.27 (d, J = 7.2 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3) syn: δ = 201.7, 143.1, 139.6, 135.8, 133.2, 129.3,
128.6, 128.3, 128.1, 127.4, 127.3, 127.0, 126.5, 59.6, 46.6, 21.4, 14.3
ppm. HRMS (ESI) syn: calcd. for C23H23NNaO3S [M]+ 416.1291;
1
found 416.1307. H NMR (400 MHz, CDCl3) anti: δ = 7.72–7.68
(m, 2 H), 7.57–7.51 (m, 3 H), 7.40–7.35 (m, 2 H), 7.14–7.03 (m, 7
H), 6.46 (d, J = 9.0 Hz, 1 H), 4.74 (dd, J = 4.7, 9.0 Hz, 1 H), 3.92
(dq, J = 4.7, 7.3 Hz, 1 H), 2.33 (s, 3 H), 1.30 (d, J = 7.3 Hz, 1 H)
ppm. 13C NMR (100 MHz, CDCl3) anti: δ = 203.9, 142.7, 139.5,
138.1, 136.3, 133.5, 129.1, 128.6, 128.23, 128.20, 127.2, 126.9, N-[1-(3-Bromophenyl)-2-methyl-3-oxo-3-phenylpropyl]-4-methyl-
126.6, 60.7, 46.0, 21.4, 16.7 ppm. HRMS (ESI) anti: calcd. for
benzenesulfonamide (37): syn-37/anti-37 = 56:44 (141 mg, 75%),
C23H23NNaO3S [M]+ 416.1291; found 416.1266.
white powder. 1H NMR (400 MHz, CDCl3) syn, anti: δ = 7.88–
Eur. J. Inorg. Chem. 2012, 1517–1530
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
1527

B. Martín-Matute et al.
FULL PAPER
6.85 (m, 13 H), 6.78 (anti) (d, J = 9.2 Hz, 1 H), 5.82 (syn) (br. s, 1
7.38–7.30 (m, 2 H), 7.20 (dd, J = 1.9, 8.5 Hz, 1 H), 6.87 (d, J =
H), 5.06 (anti) (dd, J = 4.1, 9.2 Hz, 1 H), 4.85 (syn) (t, J = 5.6 Hz, 8.1 Hz, 2 H), 6.60 (d, J = 9.0 Hz, 1 H), 4.90 (dd, J = 5.2, 9.0 Hz,
1 H), 4.10 (anti) (dq, J = 4.1, 7.1 Hz, 1 H), 4.05 (syn) (br. s, 1 H), 1 H), 4.03 (dq, J = 5.2, 7.2 Hz, 1 H), 2.11 (s, 3 H), 1.35 (d, J =
2.32 (anti) (s, 3 H), 2.27 (syn) (s, 3 H), 1.33 (anti) (d, J = 7.1 Hz, 3
H), 1.23 (syn) (br. s, 3 H) ppm. 13C NMR (100 MHz, CDCl3) syn,
anti (one carbon atom is missing due to overlap): δ = 204.0 (anti);
7.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3) anti: δ = 203.8,
142.7, 137.9, 136.4, 136.2, 133.5, 132.9, 132.5, 129.0, 128.6, 128.21,
128.17, 127.9, 127.4, 126.9, 126.2, 126.0, 125.9, 124.4, 61.0, 45.9,
202.2 (syn), 143.1, 142.9, 138.4, 137.7, 137.5 (syn), 136.2, 135.4 21.1, 16.9 ppm. HRMS (ESI) anti: calcd. for C27H25NNaO3S
(syn), 133.6, 133.5, 133.0 (syn), 132.6, 131.1 (syn), 129.24, 129.22, [M]+ 466.1447; found 466.1443.
129.1, 128.9 (syn), 128.64, 128.62, 128.5, 128.4 (syn), 128.2, 127.4
4-Methyl-N-[2-methyl-3-(naphthalen-1-yl)-3-oxo-1-phenylpropyl]-
(syn), 127.3, 127.2, 126.9, 122.2 (anti), 121.9 (syn), 59.5 (anti), 57.6
benzenesulfonamide (41): syn-41:anti-41 = 84:16 (122 mg, 69%),
(syn), 42.8 (anti), 42.3 (syn), 21.42, 21.40, 16.7 (anti), 11.5 (syn)
white powder. 1H NMR (400 MHz, CDCl3) syn: δ = 8.10–8.03 (m,
ppm. HRMS (ESI): calcd. for C23H22BrNNaO3S [M]+ 494.0396;
1 H), 7.96–7.90 (m, 1 H), 7.86–7.81 (m, 1 H), 7.58–7.45 (m, 5 H),
found 494.0379.
7.43–7.37 (m, 1 H), 7.14–7.04 (m, 7 H), 5.27 (d, J = 7.9 Hz, 1 H),
4.72 (t, J = 7.9 Hz, 1 H), 3.84 (app. quint, J = 7.5 Hz, 1 H), 2.32
(s, 3 H), 1.36 (d, J = 7.1 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3) syn: δ = 205.7, 143.1, 139.4, 137.0, 135.8, 133.8, 132.6,
130.2, 129.3, 128.4, 128.3, 127.8, 127.5, 127.3, 127.2, 126.6, 126.5,
125.4, 124.1, 59.9, 50.8, 21.4, 14.6 ppm. HRMS (ESI) syn: calcd.
for C27H25NNaO3S [M]+ 466.1447; found 466.1460. 1H NMR
(400 MHz, CDCl3) anti: δ = 8.24–8.17 (m, 1 H), 7.97–7.87 (m, 1
H), 7.87–7.80 (m, 1 H), 7.62–7.49 (m, 4 H), 7.37–7.25 (m, 2 H),
7.11 (s, 5 H), 7.10–7.04 (m, 2 H), 6.64 (d, J = 8.7 Hz, 1 H), 4.80
(dd, J = 4.8, 8.7 Hz, 1 H), 3.89 (adq, J = 4.8, 7.2 Hz, 1 H), 2.33 (s,
3 H), 1.35 (d, J = 7.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3)
anti: δ = 208.1, 142.7, 139.7, 138.1, 135.9, 133.8, 132.8, 130.1, 129.2,
128.37, 128.36, 128.0, 127.3, 127.1, 126.9, 126.7, 126.6, 125.4,
124.1, 60.9, 50.1, 21.4, 16.4 ppm. HRMS (ESI): calcd. for
C27H25NNaO3S [M]+ 466.1447; found 466.1447.
4-Methyl-N-[2-methyl-3-oxo-3-phenyl-1-(o-tolyl)propyl]benzene-
sulfonamide (38): syn-38:anti-38 = 66:34 (114 mg, 70%), white pow-
der. 1H NMR (400 MHz, CDCl3) syn: δ = 7.74–7.67 (m, 2 H),
7.54–7.47 (m, 3 H), 7.40–7.33 (m, 2 H), 7.25–7.20 (m, 1 H), 7.10–
7.04 (m, 2 H), 7.03–6.94 (m, 2 H), 6.93–6.87 (m, 1 H), 5.55 (d, J
= 7.5 Hz, 1 H), 4.86 (t, J = 7.5 Hz, 1 H), 3.91 (dq, J = 7.1, 7.5 Hz,
1 H), 2.33 (s, 3 H), 2.21 (s, 3 H), 1.33 (d, J = 7.1 Hz, 3 H) ppm.
13C NMR (100 MHz, CDCl3) syn: δ = 202.0, 143.0, 138.0, 137.1,
136.1, 135.3, 133.2, 130.4, 129.2, 128.5, 128.0, 127.3, 127.1, 126.5,
126.1, 55.2, 46.0, 21.4, 19.3, 14.9 ppm. HRMS (ESI) syn: calcd. for
C
24H25NNaO3S [M]+ 430.1447; found 430.1450. 1H NMR
(400 MHz, CDCl3) anti: δ = 7.69–7.61 (m, 2 H), 7.56–7.43 (m, 3
H), 7.41–7.32 (m, 2 H), 7.08–7.00 (m, 3 H), 6.98–6.90 (m, 2 H),
6.84–6.75 (m, 1 H), 6.39 (d, J = 8.5 Hz, 1 H), 4.98 (dd, J = 4.9,
8.5 Hz, 1 H), 3.82 (dq, J = 4.9, 7.3 Hz, 1 H), 2.38 (s, 3 H), 2.32 (s,
3 H), 1.29 (d, J = 7.3 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3)
anti: δ = 204.0, 142.6, 137.9, 137.5, 136.5, 134.3, 133.4, 130.3, 129.0,
128.6, 128.1, 127.0, 126.8, 126.5, 126.0, 56.6, 44.3, 21.4, 19.3, 16.7
ppm. HRMS (ESI) anti: calcd. for C24H25NNaO3S [M]+ 430.1447;
found 430.1436.
N-(2-Benzyl-3-oxo-1-phenylbutyl)-4-methylbenzenesulfonamide (42):
syn-42/anti-42 = 49:51 (129 mg, 79 %), white powder. 1H NMR
(400 MHz, CDCl3) syn, anti: δ = 7.58–7.50 (m, 4 H), 7.32–7.92 (m,
24 H), 6.37 (anti) (br. s, 1 H), 5.57 (syn) (br. s, 1 H), 4.68 (anti) (dd,
J = 4.9, 9.2 Hz, 1 H), 4.49 (syn) (t, J = 8.7 Hz, 1 H), 3.28–3.15 (m,
3 H), 3.00–2.93 (m, 1 H), 2.91–2.79 (m, 2 H), 2.35 (syn) (s, 3 H),
4-Methyl-N-[2-methyl-3-oxo-3-phenyl-1-(p-tolyl)propyl]benzene-
sulfonamide (39): syn-39/anti-39 = 53:47 (114 mg, 70%), white pow-
der. 1H NMR (400 MHz, CDCl3) syn: δ = 7.77–7.71 (m, 2 H),
7.57–7.50 (m, 3 H), 7.43–7.36 (m, 2 H), 7.11–7.05 (m, 2 H), 7.04–
6.91 (m, 4 H), 5.25 (br. s, 1 H), 4.57 (t, J = 7.1 Hz, 1 H), 3.87 (app.
quint, J = 7.1 Hz, 1 H), 2.34 (s, 3 H), 2.24 (s, 3 H), 1.26 (d, J =
7.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3) syn: δ = 201.4,
143.4, 138.5, 136.7, 135.6, 133.5, 131.3, 129.4, 128.9, 128.7, 128.1,
2.33 (anti) (s, 3 H), 1.59 (anti) (s, 3 H), 1.41 (syn) (s, 3 H) ppm. 13
C
NMR (100 MHz, CDCl3) syn, anti: δ = 213.2, 210.4, 143.3, 142.8,
139.1, 138.7, 138.6, 138.1, 138.0, 137.1, 129.4, 129.2, 128.9, 128.83,
128.75, 128.6, 128.5, 128.4, 127.7, 127.3, 127.2, 126.93, 126.91,
126.8, 126.5, 126.3, 60.6, 59.43, 59.40, 58.9, 36.8, 35.8, 33.1, 32.7,
21.30, 21.29 ppm. HRMS (ESI): calcd. for C24H25NNaO3S [M]+
430.1447; found 430.1468.
1
127.2, 121.4, 59.1, 46.3, 21.5, 21.0, 14.3 ppm. H NMR (400 MHz,
N-[3-(4-Chlorophenyl)-2-methyl-3-oxo-1-phenylpropyl]-4-methyl-
benzenesulfonamide (43): syn-43:anti-43 = 60:40 (136 mg, 80%),
white powder. 1H NMR (400 MHz, CDCl3) syn: δ = 7.69–7.64 (m,
2 H), 7.55–7.49 (m, 2 H), 7.39–7.34 (m, 2 H), 7.17–7.04 (m, 7 H),
5.22 (d, J = 7.7 Hz, 1 H), 4.61 (t, J = 7.5 Hz, 1 H), 3.82 (app. quint,
J = 7.2 Hz, 1 H), 2.35 (s, 3 H), 1.26 (d, J = 7.1 Hz, 3 H) ppm. 13C
NMR (100 MHz, CDCl3) syn: δ = 200.4, 143.2, 139.8, 139.3, 136.7,
134.1, 129.5, 129.3, 128.9, 128.4, 127.6, 127.3, 126.9, 59.5, 46.7,
21.4, 13.9 ppm. HRMS (ESI) syn: calcd. for C23H22ClNNaO3S
[M]+ 450.0898; found 450.0901. 1H NMR (400 MHz, CDCl3) anti:
δ = 7.67–7.60 (m, 2 H), 7.56–7.50 (m, 2 H), 7.36–7.30 (m, 2 H),
7.11–7.00 (m, 7 H), 6.37 (d, J = 8.8 Hz, 1 H), 4.73 (dd, J = 5.2,
8.8 Hz, 1 H), 3.86 (dq, J = 5.2, 7.2 Hz, 1 H), 2.33 (s, 3 H), 1.26 (d,
J = 7.3 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3) anti: δ =
202.7, 142.8, 140.0, 139.3, 137.9, 134.6, 129.6, 129.1, 128.9, 128.3,
127.3, 126.9, 126.5, 60.6, 46.0, 21.4, 16.6 ppm. HRMS (ESI) anti:
calcd. for C23H22ClNNaO3S [M]+ 450.0898; found 450.0920.
CDCl3) anti: δ = 7.77–7.70 (m, 2 H), 7.57–7.49 (m, 3 H), 7.42–7.35
(m, 2 H), 7.11–7.05 (m, 2 H), 6.96–6.85 (m, 2 H), 6.38 (d, J =
9.0 Hz, 1 H), 4.69 (dd, J = 5.1, 9.0 Hz, 1 H), 3.90 (dq, J = 5.1,
7.3 Hz, 1 H), 2.35 (s, 3 H), 2.21 (s, 3 H), 1.27 (d, J = 7.3 Hz, 3 H)
ppm. 13C NMR (100 MHz, CDCl3) anti: δ = 203.9, 142.6, 138.1,
136.8, 136.5, 136.3, 133.4, 129.1, 128.9, 128.6, 128.2, 127.0, 126.6,
60.5, 46.1, 21.4, 20.9, 16.6 ppm. HRMS (ESI) syn, anti: calcd. for
C24H25NNaO3S [M]+ 430.1447; found 430.1440.
4-Methyl-N-[2-methyl-1-(naphthalen-2-yl)-3-oxo-3-phenylpropyl]-
benzenesulfonamide (40): syn-40/anti-40 = 61:39 (135 mg, 76%),
white powder. 1H NMR (400 MHz, CDCl3) syn: δ = 7.77–7.65 (m,
3 H), 7.63–7.56 (m, 2 H), 7.53–7.26 (m, 9 H), 6.88 (d, J = 8.1 Hz,
2 H), 5.89 (d, J = 8.2 Hz, 1 H), 4.85 (t, J = 8.1 Hz, 1 H), 4.05 (to
dq, J = 7.2, 8.1 Hz, 1 H), 2.13 (s, 3 H), 1.36 (d, J = 7.2 Hz, 3 H)
ppm. 13C NMR (100 MHz, CDCl3) syn: δ = 201.6, 143.1, 136.9,
136.5, 135.8, 133.2, 132.9, 132.5, 129.1, 128.6, 128.3, 128.1, 127.9,
127.4, 127.2, 126.8, 126.0, 125.9, 124.4, 59.9, 46.5, 21.2, 14.8 ppm.
HRMS (ESI) syn: calcd. for C27H25NNaO3S [M]+ 466.1447; found
Preparation of 45 from 50: nBuLi (15 μL, 0.15 mmol, 1 m in hex-
anes) was added to an NMR tube that contained [D6]benzene
466.1437. 1H NMR (400 MHz, CDCl3) anti: δ = 7.78–7.67 (m, 3 (0.4 mL) and 2a (17 μL, 0.13 mmol) under a nitrogen atmosphere.
H), 7.61–7.54 (m, 2 H), 7.52–7.45 (m, 3 H), 7.44–7.38 (m, 3 H),
1H NMR (400 MHz, [D6]benzene, selected peaks): δ = 7.47–7.34
1528
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Eur. J. Inorg. Chem. 2012, 1517–1530

Synthesis of Functionalized Ketones from Allylic Alcohols
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(m, 2 H), 7.33–7.27 (m, 2 H), 7.21–7.15 (m, 1 H), 6.01 (br. s, 1 H),
5.22 (d, 1 H, J = 16.8 Hz), 5.16 (br. s, 1 H), 5.00 (d, 1 H, J =
9.2 Hz) ppm. A solution of 50 (186 μL, 0.05 mmol, 0.27 m in
[D6]benzene) was added to an NMR tube that contained 1a (30 mg,
0.047 mmol) in [D6]benzene (0.2 mL) under a nitrogen atmosphere.
When the tube was shaken vigorously, the mixture changed color
from yellow to red. Slow formation of 45[6a] was observed by 1H
NMR spectroscopy.
[4]
[5]
Preparation of 45 from 51: NaHMDS (70 μL, 0.14 mmol, 2 m in
THF) was added to an NMR tube that contained [D6]benzene
(0.4 mL) and 2a (17 μL, 0.13 mmol) under a nitrogen atmosphere.
1
Compound 51 was formed quantitatively within a few seconds. H
NMR (400 MHz, [D6]benzene): δ = 7.70–7.64 (m, 2 H), 7.41–734
(m, 2 H), 7.23–7.17 (m, 1 H), 6.33 (ddd, 1 H, J = 6.0, 10.1,
17.2 Hz), 5.60 (d, 1 H, J = 5.6 Hz), 5.09 (dt, 1 H, J = 17.4, 1.9 Hz),
5.09 (d, 1 H, J = 10.2 Hz) ppm. A solution of 51 (185 μL,
0.05 mmol, 0.27 m in [D6]benzene) was added to an NMR tube that
contained 1a (30 mg, 0.047 mmol) in [D6]benzene (0.4 mL) under
a nitrogen atmosphere. The tube was shaken vigorously, and the
mixture of 1a and 51 changed color from yellow to red. Quantita-
tive formation of 45 was observed within a few seconds. The NMR
spectroscopic data of 45 were identical to those reported.[6a]
Preparation of 47b from 52: A solution of 5a in pentane (10 mL,
5 mmol, 0.5 m) was added to a solution of KHMDS (24 mL,
6 mmol, 0.25 m in toluene/pentane, 100:1). After precipitation, 52
was collected by filtration, washed with pentane, and stored in a
drybox.[25b] Enolate 52 was highly sensitive to moisture and could
be only characterized as a mixture of 52 and 5a in a ratio of 80:20.
1H NMR (400 MHz, [D8]THF): δ = 7.49–7.41 (m, 2 H), 7.05–6.96
(m, 2 H), 6.93–6.85 (m, 1 H), 4.13 (q, J = 6.6 Hz, 1 H), 1.57 (d, J
= 6.6 Hz, 1 H) ppm. A solution of 52 (100 μL, 0.045 mmol, 0.08 m
in [D8]THF) was added to an NMR tube that contained 1a (20 mg,
0.03 mmol) in [D8]THF (0.4 mL) under a nitrogen atmosphere. The
tube was shaken vigorously until the color of the reaction mixture
had changed from yellow to red (4 min). Analysis by 1H NMR
spectroscopy showed the formation of 47b in approximately 35%
yield, the remainder was 5a and unidentified Ru complexes. 1H
NMR (400 MHz, [D8]THF, selected peaks): δ = 3.91 (q, 1 H, J =
6.5 Hz), 1.58 (d, 1 H, J = 6.5 Hz) ppm. 13C NMR (100 MHz,
[D8]THF, selected peaks): δ = 203.8, 202.2, 201.0, 198.7, 107.6,
27.0, 22.3 ppm. See Supporting Information for further details.
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Supporting Information (see footnote on the first page of this arti-
cle): Characterization data and copies of the NMR spectra for 11,
13–14, 18–20, 22–25, 31, and 34–43. Comparison of NMR shifts
of 47b with other C-bound ruthenium enolates reported in litera-
ture. NMR spectra of crude 45, and 49–52
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Acknowledgments
Financial support from the Swedish Research Council (veten-
skapsrådet), the Knut and Alice Wallenberg Foundation, the Swed-
ish Governmental Agency for Innovation (VINNOVA), and the
Berzelius Center EXSELENT is gratefully acknowledged. We also
thank Madeleine Livendahl for preliminary investigations of the
aldol couplings.
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Received: September 23, 2011
Published Online: December 29, 2011
1530
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Eur. J. Inorg. Chem. 2012, 1517–1530