Synthesis of (R)-BINOL-Derived (Cyclopentadienone)iron Complexes and Their Application in the Catalytic Asymmetric Hydrogenation of Ketones

Article abstract of DOI:10.1002/ejoc.201500796

A family of chiral (cyclopentadienone)iron complexes, featuring an (R)-BINOL-derived backbone, and their application in the asymmetric hydrogenation of ketones are described. The complexes differ from each other in the substituents at the 3,3′-positions of the binaphthyl residue (H, OH, OR, OCOR, OSO₂R) or at the 2,5-positions of the cyclopentadienone ring [trimethylsilyl (TMS) or Ph]. Remarkably, eight precatalysts with different 3,3′-binaphthyl substitution [(R)-1c-1j] were synthesized from a common parent complex [(R)-1b] through direct functional group interconversion reactions of the complexes. The 3,3′-(bis)methoxy-substituted precatalyst (R)-1b gave the best catalytic performance, and its application scope was assessed in the hydrogenation of several ketones. The observed ee values (up to 77%) are much higher than those previously reported for other chiral (cyclopentadienone)iron complexes.

Full text of DOI:10.1002/ejoc.201500796

FULL PAPER
DOI: 10.1002/ejoc.201500796
Synthesis of (R)-BINOL-Derived (Cyclopentadienone)iron Complexes and
Their Application in the Catalytic Asymmetric Hydrogenation of Ketones
Piotr Gajewski,[a,b] Marc Renom-Carrasco,[a,b] Sofia Vailati Facchini,[c] Luca Pignataro,*[a]
Laurent Lefort,[b] Johannes G. de Vries,[d] Raffaella Ferraccioli,[e] Umberto Piarulli,*[c] and
Cesare Gennari*[a]
Keywords: Asymmetric catalysis / Homogeneous catalysis / Hydrogenation / Iron / Ketones
A family of chiral (cyclopentadienone)iron complexes, featur-
ing an (R)-BINOL-derived backbone, and their application in
the asymmetric hydrogenation of ketones are described. The
complexes differ from each other in the substituents at the
3,3Ј-positions of the binaphthyl residue (H, OH, OR, OCOR,
OSO2R) or at the 2,5-positions of the cyclopentadienone ring
[trimethylsilyl (TMS) or Ph]. Remarkably, eight precatalysts
with different 3,3Ј-binaphthyl substitution [(R)-1c–1j] were
synthesized from a common parent complex [(R)-1b] through
direct functional group interconversion reactions of the com-
plexes. The 3,3Ј-(bis)methoxy-substituted precatalyst (R)-1b
gave the best catalytic performance, and its application
scope was assessed in the hydrogenation of several ketones.
The observed ee values (up to 77%) are much higher than
those previously reported for other chiral (cyclopenta-
dienone)iron complexes.
processes. However, the use of “noninnocent” ligands [i.e.,
those able to modify the redox properties of the metal and/
or to interact with the reactant(s)] may “force” the Fe cata-
lyst to follow reactivity patterns different from the more
common ones.[3] This approach has been applied extensively
to Fe-catalyzed reductions[4] such as hydrogenation (of ole-
fins,[5] ketones,[6] imines,[6c] esters[4a,7] and carbon dioxide/
sodium hydrogen carbonate)[8] and transfer hydrogenation
(of ketones[9] and imines).[9c,10] (Cyclopentadienone)iron
complexes A[11] (Scheme 1) perhaps represent the most im-
pressive application of this concept.[12] Analogously to what
is reported for the Shvo Ru catalyst,[13] the shuttling of the
ligand between its two cyclopentadienone/hydroxycyclo-
Introduction
The development of homogeneous catalytic methodolo-
gies based on first-row transition metals is becoming an in-
dustrially relevant task, owing to the high price and limited
stock of noble metals. Indeed, first-row transition metals
such as Fe, Co, Ni and Cu are far more abundant and,
generally, less toxic than their second- and third-row coun-
terparts, which have been employed intensely in homogen-
eous catalysis. In particular, Fe is readily available (second
most abundant metal in the earth’s crust) and has a lower
toxicity than those of most other transition metals. As such,
Fe has been employed widely in heterogeneous catalysis
(e.g., in the Haber process for the synthesis of ammonia).[1]
On the contrary, the use of Fe in homogeneous catalysis has
been relatively limited,[2] possibly because of its tendency
to engage in radical reactions rather than in two-electron
pentadienyl forms enables
a
Fe0/FeII catalytic cycle
(Scheme 1, Cycle I), which is uncharacteristic of more clas-
sical Fe complexes. The active cyclopentadienone(iron)
complexes act-A are able to split H2 and, thus, catalyze the
hydrogenation of carbonyl compounds through a concerted
outer-sphere mechanism, in which the ligand is involved
again through its OH group.[14]
This catalytic Cycle I (Scheme 1) can be accessed either
from the cyclopentadienone(iron) complexes act-A, gener-
ated in situ from complexes A by creation of a vacant coor-
dination site (by reaction with Me3NO[15] or UV light),[16]
or from the (hydroxycyclopentadienyl)iron complexes B.
The latter can be either preisolated (as in the seminal work
of Casey and Guan)[17] or generated in situ by reaction of
A with an aqueous base.[18] The in situ activation protocols
have the advantage of employing the stable complexes A
(which can be handled in air) and avoid the direct manipu-
lation of the highly air- and moisture-sensitive compounds
[a] Università degli Studi di Milano, Dipartimento di Chimica,
Via C. Golgi 19, 20133 Milan, Italy
E-mail: luca.pignataro@unimi.it
cesare.gennari@unimi.it
http://eng.chimica.unimi.it/ecm/home
[b] DSM Chemical Technology R&D BV,
P. O. Box 18, 6160 MD Geleen, The Netherlands
[c] Università degli Studi dell’Insubria, Dipartimento di Scienza e
Alta Tecnologia,
Via Valleggio 11, 22100 Como, Italy
E-mail: umberto.piarulli@uninsubria.it
http://www4.uninsubria.it/on-line/home.html
[d] Leibniz-Institut für Katalyse e. V. an der Universitt Rostock,
Albert-Einstein-Straße 29a, 18059 Rostock, Germany
[e] CNR, Istituto di Scienze e Tecnologie Molecolari (ISTM)
Via C. Golgi 19, 20133 Milan, Italy
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500796.
5526
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5526–5536

Catalytic Asymmetric Hydrogenation of Ketones
Scheme 1. Catalytic pathways of (i) hydrogenation of C=O and C=N double bonds (Cycle I) and (ii) Oppenauer-type alcohol oxidation
(Cycle II) catalyzed by cyclopentadienone complexes act-A.
B. Owing to their easy preparation and interesting catalytic et al. (Figure 1, b),[15d] but their use in ketone reduction led
properties, complexes A and B have become the object of only to modest enantioselectivities (up to 31% ee).
increasing interest among organic chemists: they have been
To fill this gap, our research group has recently devel-
employed successfully to promote the hydrogenation of oped a new class of A-type complexes featuring a chiral
C=O[15a,15e,18,19a] and C=N bonds[15b,15c,15e,19b,19c] as well as backbone derived from (R)-BINOL.[24] In this paper, we
the transfer hydrogenation of ketones.[15d,20] Moreover, present a full account of the synthesis of 11 members of
through the same mechanism (Scheme 1, Cycle II) they also this family of chiral complexes. Their use as precatalysts for
catalyze the Oppenauer-type dehydrogenation of alcohols the asymmetric hydrogenation (AH) of ketones allowed us
to carbonyl compounds[21] as well as the amination of to obtain the highest ee ever reported with (cyclopenta-
alcohols through a “hydrogen-borrowing” reaction.[22]
Despite this burgeoning interest, the applications of com-
plexes A and B in enantioselective reductions remain scarce;
the most successful example was the cooperative iron–
Brønsted acid catalysis developed by Beller and co-workers
for the hydrogenation of imines[19c] and quinoxalines.[19b]
However, in the latter case, an achiral B-type complex was
used, and the enantiodiscrimination stems from chiral
phosphoric acid derivatives.[23] Chiral A-type complexes
were developed by Berkessel et al. (Figure 1, a)[16] and Wills
dienone)iron complexes.
Results and Discussion
We selected (R)-BINOL as a cheap and readily available
chiral building block for the synthesis of our (cyclopenta-
dienone)iron complexes 1 (Figure 2, a). In the pericyclic
transition state commonly accepted for ketone hydrogen-
ation (Figure 2, b),[14,17b] the substrate is located at a re-
markable distance from the binaphthyl stereoaxis. For this
reason, we expected that the substituents at the 3,3Ј-posi-
tions of the binaphthyl moiety[25] and at the 2,5-positions
of the cyclopentadienone ring would influence the transfer
Figure 2. (a) General structure of chiral precatalysts 1 and (b) ex-
pected importance of the binaphthyl 3,3Ј-substituents and cyclo-
pentadienone 2,5-substituents in AH.
Figure 1. Previously reported methods for the enantioselective re-
duction of ketones catalyzed by chiral A-type complexes.
Eur. J. Org. Chem. 2015, 5526–5536
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5527

L. Pignataro, U. Piarulli, C. Gennari et al.
FULL PAPER
of stereochemical information. Thus, we synthesized several
derivatives, each differing in the substituents at these “cru-
cial” positions.
Firstly, the 3,3Ј-unsubstituted complex (R)-1a was syn-
thesized in three steps from the commercially available com-
pound (R)-2 according to the procedure shown in
Scheme 2.[24]
Scheme 4. Synthesis of the 3,3Ј-disubstituted precatalyst (R)-1b.[24]
presence of (R)-1b allowed the identification of the optimal
conditions for AH, and these conditions were adopted for
the substrate screening (Table 1).[24] Notably, the use of
Me3NO for precatalyst activation led to higher and more
reproducible conversions than those obtained with the ini-
[18]
Scheme 2. Synthesis of the precatalyst (R)-1a.[24]
tially used K2CO3 (84% instead of 54% conversion with
1 mol-% catalyst).
Precatalyst (R)-1a was tested in the AH of acetophenone
(S1, Scheme 3) under the conditions reported by Beller and
co-workers[18] for the in situ activation of (cyclopen-
tadienone)iron complexes. A conversion of 62% into 1-
phenylethanol (P1) was observed, along with a very low
enantioselectivity (8% ee) in favor of the S enantiomer.[24]
As can be seen in Table 1, the application scope of the
precatalyst (R)-1b is quite broad and ranges from aceto-
phenones to aliphatic and cyclic ketones. As a general
trend, a larger difference in size between the substituents of
the carbonyl group leads to a higher enantiomeric excess,
which ranges from fair to good (up to 77%).
The improved enantioselectivity obtained with (R)-1b
stimulated us to prepare other precatalysts substituted at
the 3,3Ј-positions of the binaphthyl system. To this end,
rather than opting for a costly and time-consuming parallel
synthesis of each new precatalyst, we decided to directly
derivatize (R)-1b. Like other (cyclopentadienone)iron deriv-
atives A, this iron complex possesses a stability uncom-
monly high among metal complexes. Complexes 1 are stable
in air and moisture, do not decompose in column
chromatography (silica), and are also compatible with the
Scheme 3. Test of precatalyst (R)-1a in the AH of acetophenone
(S1).[24]
We attributed this low enantiomeric excess to a poor experimental conditions required for the transformation of
transfer of stereochemical information owing to the remote unreactive functional groups. Remarkably, the conversion
position of the stereoaxis with respect to the substrate in of (R)-1b into (R)-1c (Scheme 5) involved treatment with
the reaction transition state (Figure 2, b). Consequently, we BBr3 and Bu4NI at 85 °C in 1,2-dichloroethane (DCE) for
set out to synthesize the 3,3Ј-bis(methoxy) derivative (R)-1b 70 h. Despite these harsh conditions, the yield of the desired
from (R)-5, the preparation of which was described by product was 80%, and no appreciable degradation of the
Cramer and co-workers.[26] The synthesis was carried out in metal complex was observed.[24]
three steps, as shown in Scheme 4.[24]
Compound (R)-1c was characterized by single-crystal X-
The double alkynylation of bis(iodide) 6 did not occur ray diffraction analysis, and the structure is shown in Fig-
under the conditions used for the synthesis of 4 (copper- ure 3. CCDC-1037376 contains the supplementary crystal-
catalyzed reaction of the alkynyl Grignard, see Scheme 2) lographic data for this paper. These data can be obtained
but proceeded smoothly with the lithium acetylide (80% free of charge from The Cambridge Crystallographic Data
yield). On the contrary, the latter reaction was not success- Centre via www.ccdc.cam.ac.uk/data_request/cif.[24]
ful with bis(iodide) 3, which suggests that the assistance of
It was decided to use (R)-1c as a scaffold for the prepara-
the 3,3Ј-OMe groups is required for the nucleophilic substi- tion of new compounds by exploiting its 3,3Ј-hydroxy
tution by the lithium acetylide. Complex (R)-1b was tested groups for the following transformations (Scheme 5):
in the AH of S1 and showed a substantially increased (a) esterification, (b) etherification, (c) sulfonylation, poss-
enantioselectivity compared to that with (R)-1a (50 vs. ibly followed by (d) cross-coupling to form the 3,3Ј-substi-
8% ee). The optimization of the reaction parameters in the tuted derivatives. In this way, our synthetic efforts to obtain
5528
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5526–5536

Catalytic Asymmetric Hydrogenation of Ketones
Table 1. Substrate screening[a] for the act-(R)-1b-catalyzed AH.[24]
Scheme 5. General synthetic strategy for the preparation of 3,3Ј-
substituted (cyclopentadienone)iron complexes 1: (a) esterification,
(b) etherification, (c) sulfonylation, and (d) cross-coupling.
[a] Reaction conditions: substrate/(R)-1b/Me3NO 100:2:4, P
=
H2
30 bar, solvent: 5:2 iPrOH/H2O, c0 (substrate) = 1.43 m, T = 70 °C,
reaction time: 18 h. [b] Determined by GC with a chiral capillary
column (see Supporting Information). [c] Determined by GC or
HPLC with a chiral capillary column (see Supporting Infor-
mation). [d] Assigned by comparison of the sign of the optical rota-
tion with the literature data (see Supporting Information). [e] Sub-
strate/(R)-1b/Me3NO 100:5:10.
Figure 3. ORTEP diagram (CCDC-1037376) of the molecular
structure of (R)-1c (thermal ellipsoids set at the 50% probability
level). Cocrystallized solvent molecules are omitted for clarity.[24]
(R)-1c [12 steps and three chromatographic purifications
from (R)-BINOL] were leveraged towards the preparation
of several new precatalysts in just one or two steps from the
same advanced precursor.
The esterification of (R)-1c proceeded smoothly under
classical conditions [acyl chloride, triethylamine (TEA), and
catalytic 4-(dimethylamino)pyridine (DMAP) in tetra-
hydrofuran (THF) under reflux] to provide diesters (R)-1d
and (R)-1e in high yields (Scheme 6).
The etherification of (R)-1c was more problematic, as
only the bis(benzyl ether) (R)-1f could be prepared in a syn-
thetically meaningful yield (Scheme 7). Attempts to prepare Scheme 6. Synthesis of esters (R)-1d and (R)-1e.
Eur. J. Org. Chem. 2015, 5526–5536
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5529

L. Pignataro, U. Piarulli, C. Gennari et al.
FULL PAPER
the bis(isopropyl ether) under similar reaction conditions
failed, as did the preparation of the bis(tert-butyl ether) by
reaction of (R)-1c with isobutene or (tBuO)2CHNMe2.
Scheme 8. Synthesis of sulfonyl esters (R)-1g–1i.
Scheme 7. Synthesis of (R)-1c and attempted preparation of other
3,3Ј-bis(ether) derivatives.
led to almost quantitative formation of the monosubsti-
tuted product (R)-1j (Table 2, Entries 1 and 2), without any
Complex (R)-1c showed a good reactivity with meth- trace of the desired product (R)-1k. Other conditions for
anesulfonyl chloride (MsCl) and p-toluenesulfonyl chloride the Suzuki–Miyaura reaction[30,31] were screened without
(TsCl), which, in the presence of TEA and catalytic DMAP, success (Table 2, Entries 3–6). In particular, the use of rela-
allowed us to obtain (R)-1g and (R)-1h, respectively, in tively strong bases, the presence of water, or both caused
good yields (Scheme 8). To our surprise, (R)-1c did not re- the decomposition of the iron complex, probably through a
act with trifluoromethanesulfonyl chloride (TfCl) or tri- Hieber base reaction to form the sensitive B-type (hydroxy-
fluoromethanesulfonic anhydride (Tf2O) under the same cyclopentadienyl)iron complex.[29] Several other Pd- and
conditions. However, the synthesis of the 3,3Ј-bis(triflate) Ni-catalyzed cross-coupling reactions were screened (see
(R)-1i could be realized with good yield (Scheme 8) by reac- Supporting Information for the full set of employed meth-
tion of (R)-1c with the Comins reagent [N-(5-chloro-2-pyr- odologies), but (R)-1k could not be formed.
idyl)bis(trifluoromethanesulfonimide)].[27]
NMR spectroscopy analysis showed that (R)-1j (see
According to our general synthetic strategy (Scheme 5, Scheme Table 2) is a single species, not a mixture of the two
d), we tried to exploit the triflate groups of (R)-1i for the possible monosubstitution products. However, as we could
installation of aryl groups through cross-coupling reaction. not grow crystals of (R)-1j, we could not ascertain which of
The Suzuki–Miyaura cross-coupling of (R)-1i with phenyl- the two diastereotopic OTf groups of (R)-1i was replaced.
boronic acid under typical conditions for aryl triflates[28] We speculate that the OTf group of (R)-1i that did not react
Table 2. Arylation of bis-triflate (R)-1i by Suzuki–Miyaura cross-coupling.
Entry
Conditions
NMR ratio[a]
1i [%]
1j [%]
1k [%]
1[28]
2
PhB(OH)2 (2.5 equiv.), [Pd(PPh3)4] (0.1 equiv.), K3PO4 (3 equiv.), KBr (2.2 equiv.), dioxane, 85 °C
5
95
(74)
98
(80)
3
0
PhB(OH)2 (2.5 equiv.), Pd(OAc)2 (0.2 equiv.), PPh3 (0.4 equiv.), K3PO4 (3 equiv.), KBr (2.2 equiv.), dioxane, 85 °C
2
0
0
3[30]
4[31]
PhB(OH)2 (2.5 equiv.), Pd(OAc)2 (0.15 equiv.), PCy3 (0.18 equiv.), KF (3.3 equiv.), THF, 60 °C
PhB(OH)2 (5 equiv.), [Pd(PPh3)4] (0.1 equiv.), Ba(OH)2·8H2O, DME/H2O, 85 °C
97
decomposition
[a] Conversion determined by NMR spectroscopy; isolated yields are indicated in parentheses.
5530
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5526–5536

Catalytic Asymmetric Hydrogenation of Ketones
is probably the one close the Fe(CO)3 group, which is steri- Table 3. Screening of precatalysts (R)-1c–1j in the AH of aceto-
phenone.[a]
cally more hindered than the one that is more distant from
the metal center.
To achieve substitution of both OTf groups, we decided
to perform the Suzuki–Miyaura reaction of the cyclo-
pentadienone ligand 8 (Scheme 9), obtained by decomplex-
ation of (R)-1i according to the methodology reported by
Knölker and co-workers.[29] As expected, both of the homo-
topic OTf groups of 8 reacted smoothly under Suzuki–Mi-
yaura conditions[28] to yield the 3,3Ј-bis(phenyl)-substituted
cyclopentadienone 9 (Scheme 9). This result lends credit to
our hypothesis that the unreactive OTf group of complex
(R)-1i is the one close to the Fe(CO)3 group. We then tried
to prepare complex (R)-1k by reaction of 9 with Fe2(CO)9
or Fe(CO)5 in hot toluene or xylene (Scheme 6),[32] but no
reaction occurred.
Scheme 9. Attempted synthesis of (R)-1k from (R)-1i by a decom-
plexation/cross-coupling/recomplexation sequence.
The newly synthesized complexes (R)-1c–1j were
screened in the AH of acetophenone under the optimized
conditions used with (R)-1b,[24] and the results are shown
in Table 3. All complexes (R)-1c–1j (Table 3) were less active
and induced lower enantioselectivity that the parent com-
plex (R)-1b (Table 1, Entry 1). An incomplete conversion of
[a] Reaction conditions: substrate/(R)-1b/Me3NO 100:2:4, P
=
H2
the starting material was observed in all cases, and the best
conversion (63%) was obtained with (R)-1c (Table 3, En-
try 1). Moreover, only (R)-1j (Table 3, Entry 8) led to the
same level of enantioselectivity as that obtained with (R)-
1b, and all of the other precatalysts gave lower ee values
(Table 3, Entries 1–7). Although a slight decrease of
30 bar, solvent: 5:2 iPrOH/H2O, c0 (substrate) = 1.43 m, T = 70 °C,
reaction time: 18 h. [b] Determined by GC with a chiral capillary
column (MEGADEX DACTBSβ, diacetyl-tert-butylsilyl-β-cyclo-
dextrin). [c] Absolute configuration: S in all cases (assigned by
comparison of the optical rotation sign with literature data).[24]
enantioselectivity was expected for (R)-1c owing to the our synthetic efforts towards these modified analogs of (R)-
smaller size of its OH substituents compared with OMe 1b are shown in Scheme 10. The precursor diynes (R)-10
groups, we do not have a straightforward explanation for and (R)-11 were prepared by the reactions of the bis(iodide)
the low ee values observed with (R)-1d–1i, which bear 3,3Ј- (R)-6 with [(triisopropylsilyl)ethynyl]lithium and [(phenyl)-
substituents bulkier than OMe.
ethynyl]lithium, respectively (Scheme 10, a).
To assess the influence of the 2,5-substituents of the
Diyne (R)-12 was synthesized in 90% yield by desil-
cyclopentadienone ring on the catalytic performance, we ylation of (R)-7 in the presence of K2CO3 in MeOH
decided to replace the trimethylsilyl (TMS) groups of (R)- (Scheme 10, b). The cyclization of the diynes to give the
1b with triisopropylsilyl (TIPS), Ph, or H. The results of corresponding (cyclopentadienone)iron complexes was suc-
Eur. J. Org. Chem. 2015, 5526–5536
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5531

L. Pignataro, U. Piarulli, C. Gennari et al.
FULL PAPER
Scheme 10. Synthesis of (R)-1b analogs modified at the 2,5-positions of the cyclopentadienone ring.
cessful only for (R)-11, which yielded the corresponding bis- enantiomer of P1, in sharp contrast with the bis(trimethyl-
(phenyl)-substituted complex (R)-1l. Diyne (R)-10 did not silyl)-substituted precatalyst (R)-1b, which forms (S)-P1
cyclize, probably owing to the excessive steric bulk of the preferentially. This inversion in the stereochemical prefer-
TIPS groups, whereas the unprotected diyne 12 underwent ence demonstrates that the cyclopentadienone 2,5-substitu-
complete degradation under cyclization conditions.
ents play an important role in the transmission of the
The new precatalyst (R)-1l was tested in the AH of aceto- stereochemical information to the substrate, which is no less
phenone under the conditions optimized for (R)-1b important than that of the binaphthyl 3,3Ј-substituents.
(Scheme 11).
Overall, the outcome of the AH promoted by precata-
lysts (R)-1a–1l depends on a subtle interplay between the
binaphthyl 3,3Ј-substituents and the adjacent cyclopenta-
dienone 2,5-substituents, and the optimal balance (in terms
of both activity and enantiodiscrimination) was reached
with the 3,3Ј-bis(methoxy)- and 2,5-bis(trimethylsilyl)-sub-
stituted complex (R)-1b. Future work will be devoted to ra-
tionalize this interplay to develop more-efficient second-
generation precatalysts.
Scheme 11. Test of precatalyst (R)-1l in the AH of acetophenone
under the optimized conditions [substrate/(R)-1l/Me3NO 100:2:4,
Conclusions
PH = 30 bar, solvent = 5:2 iPrOH/H2O, c0 (substrate) = 1.43 m, T
2
= 70 °C, reaction time: 18 h].
We have presented a new family of chiral (cyclopenta-
Precatalyst (R)-1l gave very low conversion (6%). A pos- dienone)iron complexes [(R)-1a–1j and (R)-1l], which fea-
sible explanation for such low activity is that the phenyl ture a backbone derived from (R)-BINOL, and their use as
groups on the cyclopentadienone ring are not bulky enough precatalysts for the AH of ketones. The 3,3Ј-(bis)methoxy-
to prevent dimerization of the (R)-1l-derived B-type com- substituted complex (R)-1b provided the best conversion
plex followed by decomposition, as pointed out by Guan and ee with acetophenone; thus, (R)-1b was employed in
and co-workers for a related achiral complex.[21a] A modest substrate screening and provided up to 77% ee. These ee
enantiomeric excess (11%) was observed in favor of the R values are the highest obtained to date with chiral (cyclo-
5532
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5526–5536

Catalytic Asymmetric Hydrogenation of Ketones
pentadienone/hydroxycyclopentdienyl)iron catalysts.[15d,16]
Like other previously reported (cyclopentadienone)iron
complexes, the new compounds are highly stable and toler-
ate the conditions required for several functional-group in-
terconversion reactions. Taking advantage of this feature,
we prepared seven complexes with different substituents at
the 3,3Ј-positions of the binaphthyl moiety [(R)-1d–1j] from
the common precursor (R)-1c, which in turn was prepared
by demethylation of (R)-1b.[24] Substitution at the 3,3Ј-posi-
chromatography was performed with a GC instrument equipped
with a flame ionization detector and a chiral capillary column.
High-resolution mass spectrometry (HRMS) was performed with
a Fourier transform ion cyclotron resonance (FTICR) Mass Spec-
trometer APEX II with a 4.7 T Magnet (Magnex) and an ESI
source at CIGA (Centro Interdipartimentale Grandi Apparecchiat-
ure) c/o Università degli Studi di Milano; the Xmass software
(Bruker Daltonics) was used. Elemental analyses were performed
with a Perkin–Elmer Series II CHNS/O Analyzer 2000. The X-ray
intensity data were collected with a Bruker Apex II CCD area de-
tions of the binaphthyl system affected both the activity and tector by using graphite-monochromated Mo-Kα radiation.
the enantioselectivity in an unclear manner, and (R)-1b re-
General Procedure for the Asymmetric Hydrogenation: Hydrogen-
mained the best precatalyst. The synthesis of analogs of
ations were performed in a 450 mL Parr autoclave equipped with
(R)-1b featuring different substituents at the 2,5-positions
a removable aluminum block that can accommodate up to fifteen
magnetically stirred 7 mL glass vials. The catalyst (0.01 mmol,
2 mol-%) was weighed into glass vials, which were accommodated
of the cyclopentadienone ring was then undertaken, and the
2,5-bis(phenyl)-substituted compound (R)-1l was prepared.
Compared to (R)-1b, the latter complex showed low cata- in the aluminum block after the addition of magnetic stir bars to
each of them. The block was placed in a Schlenk tube, which was
then subjected to three vacuum–nitrogen cycles. iPrOH (0.25 mL)
was added to each vial, and stirring was started. Me3NO
(0.02 mmol, 4 mol-%) was added to each vial as an H2O solution
(0.1 mL). The mixtures were stirred at room temperature under ni-
trogen for 10 min, and then the substrate (0.5 mmol) was added.
Each vial was capped with a Teflon septum pierced by a needle,
the block was transferred into the autoclave, and stirring was
started. After four purges with hydrogen at the selected pressure,
heating was started. The reaction mixtures were stirred under
hydrogen pressure overnight and then analyzed for conversion and
ee determination.
lytic activity and the opposite stereochemical preference in
the AH of acetophenone. This finding suggests that both
the binaphthyl 3,3Ј-substituents and the cyclopentadienone
2,5-substituents of the new catalysts play a role in the trans-
mission of the stereochemical information.
Experimental Section
General Remarks: All reactions were performed in flame-dried
glassware with magnetic stirring under an inert atmosphere (nitro-
gen or argon), unless otherwise stated. The solvents for the reac-
tions were distilled from the following drying agents and transfer-
red under nitrogen: CH2Cl2 (CaH2), MeOH (CaH2), THF (Na),
dioxane (Na), toluene (Na), Et3N (CaH2). Dry dichloroethane,
N,N-dimethylformamide (DMF), dimethoxyethane, 2-propanol,
ethanol, acetone, and CHCl3 (over molecular sieves in bottles with
crown caps) were purchased from Sigma–Aldrich and stored under
nitrogen. The reactions were monitored by analytical thin-layer
chromatography (TLC) with silica gel 60 F254 precoated glass
plates (0.25 mm thickness). Visualization was accomplished by irra-
diation with a UV lamp, staining with a potassium permanganate
alkaline solution, or both. Flash column chromatography was per-
formed with silica gel (60 Å, particle size 40–64 μm) as the station-
ary phase by following the procedure of Still and co-workers.[33]
The 1H NMR spectra were recorded with a spectrometer operating
at 400.13 MHz. The 1H chemical shifts (δ) are reported in ppm
with the solvent signal relative to tetramethylsilane employed as the
internal standard (CDCl3 δ = 7.26 ppm, CD2Cl2 δ = 5.32 ppm,
[D]6acetone δ = 2.05 ppm). The following abbreviations are used to
describe spin multiplicity: s = singlet, d = doublet, t = triplet, q =
quartet, m = multiplet, br = broad signal, dd = doublet of doublets,
ddd = doublet of doublets- of doublets, td = triplet of doublets.
The 13C NMR spectra were recorded with a 400 MHz spectrometer
operating at 100.56 MHz with complete proton decoupling. The
13C chemical shifts are reported in ppm (δ) relative to tetramethyl-
silane with the respective solvent resonance as the internal standard
(CDCl3 δ = 77.16 ppm, CD2Cl2 δ = 54.00 ppm, [D]6acetone δ =
29.84, 206.26 ppm). The 19F NMR spectra were recorded with a
300 MHz spectrometer operating at 282 MHz. The 19F NMR
chemical shifts are reported in ppm relative to external CFCl3 at δ
= 0 ppm (positive values downfield). The coupling constants are
given in Hz. The infrared spectra were recorded with a standard
FTIR spectrometer. The optical rotation values were measured
with an automatic polarimeter with a 1 dm cell at the sodium D
Complex (R)-1a: Diyne 4 (0.510 g, 1.07 mmol, 1 equiv.) and
Fe2(CO)9 (0.781 g, 2.14 mmol, 2 equiv.) were dissolved in toluene
(9 mL) and heated to 90 °C for 4 h. After cooling to room tempera-
ture, the reaction mixture was filtered through a pad of Celite
[rinsed with dichloromethane (DCM)]. The filtrate was concen-
trated in vacuo, and the residue was purified by flash column
chromatography (8:2 hexane/DCM) to afford (R)-1a as a pale yel-
low solid, yield 0.320 g (46%); m.p. 209 °C (dec.). [α]1D9 = –32.24 (c
1
3
= 0.9, DCM). H NMR (400 MHz, CD2Cl2): δ = 8.04 [d, J(H,H)
3
3
= 8.5 Hz, 2 H], 7.99 [d, J(H,H) = 8.8 Hz, 1 H], 7.97 [d, J(H,H)
3
3
= 8.8 Hz, 1 H], 7.68 [d, J(H,H) = 8.5 Hz, 1 H], 7.55 [d, J(H,H)
= 8.5 Hz, 1 H], 7.52–7.45 (m, 2 H), 7.30 [td, 3J(H,H) = 8.5, 4J(H,H)
= 1.1 Hz, 1 H], 7.25 [td, 3J(H,H) = 8.5, 4J(H,H) = 1.1 Hz, 1 H],
7.20 [d, J(H,H) = 8.5 Hz, 1 H], 7.09 [d, J(H,H) = 8.5 Hz, 1 H],
3.76 [d, 2J(H,H) = 15.7 Hz, 1 H], 3.67 [d, 2J(H,H) = 14.1 Hz, 1 H],
3.45 [d, 2J(H,H) = 15.7 Hz, 1 H], 3.38 [d, 2J(H,H) = 14.1 Hz, 1 H],
0.41 (s, 9 H), 0.26 (s, 9 H) ppm. 13C NMR (100 MHz, CD2Cl2): δ
= 209.8, 181.4, 137.0, 135.6, 135.0, 134.6, 133.4, 132.5, 130.0, 129.7,
128.9, 128.7, 127.5, 127.3, 127.1, 127.0, 126.9, 126.5, 113.1, 111.5,
3
3
76.0, 74.0, 34.8, 32.8, 0.9, 0.5 ppm. IR (film): ν = 3054.69, 2953.93,
˜
2060.1, 2005.1, 1985.4, 1626.2, 1507.6, 1429.5, 1264.1, 1248.7 cm–1.
HRMS (ESI+): calcd. for C36H35O4Si2Fe [M + H]+ 643.14294;
found 643.14164.
Complex (R)-1b: Diyne 7 (3.27 g, 6.11 mmol, 1 equiv.) and Fe2(CO)
(4.55 g, 12.5 mmol, 2 equiv.) were dissolved in toluene (45 mL)
9
and heated to 90 °C for 4.5 h. After cooling to room temperature,
the reaction mixture was filtered through a pad of Celite (rinsed
with DCM). The filtrate was concentrated in vacuo, and the residue
was purified by flash column chromatography (93:7 hexane/AcOEt)
to afford (R)-1b as a pale yellow solid, yield 2.88 g (67% yield);
m.p. 233–237 °C (dec.). [α]2D3 = –129.38 (c = 0.41, DCM). 1H NMR
3
(400 MHz, CDCl3): δ = 7.84 (m, 2 H), 7.42 [t, J(H,H) = 7.2 Hz,
line (λ = 589 nm) or with a Hg lamp at λ = 436 nm. Gas 2 H], 7.33 (s, 1 H), 7.30 (s, 1 H), 7.11–7.03 (m, 2 H), 6.92 [d,
Eur. J. Org. Chem. 2015, 5526–5536
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5533

L. Pignataro, U. Piarulli, C. Gennari et al.
FULL PAPER
3J(H,H) = 8.4 Hz, 2 H], 4.37 [d, J(H,H) = 15.5 Hz, 1 H], 4.15 [d, 1 equiv.), Et3N (41 μL, 0.3 mmol, 4 equiv.), and DMAP (0.8 mg,
2
2J(H,H) = 13.7 Hz, 1 H], 4.04 (s, 3 H), 3.94 (s, 3 H), 3.26 [d,
0.007 mmol, 0.1 equiv.) in THF (1 mL), and the mixture was heated
under reflux for 4 h. After this time, the mixture was diluted with
2J(H,H) = 13.7 Hz, 1 H], 3.12 [d, J(H,H) = 15.5 Hz, 1 H], 0.43 (s,
2
9 H), 0.32 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 208.7, DCM and washed with 0.5 m HCl (2ϫ 5 mL), saturated aqueous
181.1, 155.1, 154.8, 138.6, 137.2, 133.9, 133.8, 127.4, 127.2, 127.1,
127.0, 126.9, 126.8, 126.6, 126.5, 126.4, 124.3, 124.1, 115.4, 107.8,
NaHCO3 (5 mL), and brine (5 mL). The organic phase was then
dried with Na2SO4. After concentration, the pure complex (R)-1e
106.3, 105.7, 75.2, 74.9, 55.6, 54.8, 26.3, 26.2, 0.7, 0.2 ppm. IR was obtained as a pale yellow solid after purification by flash col-
(film): ν = 3059.5, 2960.2, 2169.0, 2059.6, 2004.2, 1987.3, 1620.4, umn chromatography (95:5 to 9:1 hexane/AcOEt), yield 53 mg
˜
27
1
1598.7, 1454.1, 1246.3, 1111.3 cm–1. HRMS (ESI+): calcd. for (81%); m.p. 176 °C (dec.). [α] = –108.6 (c = 0.25 in DCM). H
436
C38H39O6Si2Fe [M + H]+ 703.16410; found 703.16264.
NMR (400 MHz, CDCl3): δ = 8.26 (m, 1 H), 8.24 (m, 1 H), 8.21
3
(m, 1 H), 8.19 (m, 1 H), 7.92 [d, J(H,H) = 4.7 Hz, 1 H], 7.90 [d,
Complex (R)-1c: In a Schlenk tube fitted with a Teflon screw cap,
BBr3 (1 m DCM solution, 14.0 mL, 14.0 mmol, 10 equiv.) was
added dropwise to a stirred solution of (R)-1b (0.99 g, 1.41 mmol,
1 equiv.) and Bu4NI (1.30 g, 3.52 mmol, 2.5 equiv.) in DCE
(40 mL) at 0 °C. The Schlenk tube was sealed, and the mixture was
heated to 84 °C and stirred for 3 d. After this time, the reaction
mixture was cooled to 0 °C, and ice-cold H2O (50 mL) was added.
The mixture was extracted with DCM (3ϫ 20 mL), washed with
brine (30 mL), and then dried with Na2SO4. Filtration of the DCM
solution through a short pad of silica allowed the removal of the
ammonium salts (which eluted before the product), and then com-
plex (R)-1c was obtained as a pale yellow solid after purification
by flash column chromatography (83:17 to 77:23 hexane/AcOEt),
yield 0.762 g (80%); m.p. 187–195 °C (dec.). [α]2D3 = –115.07 (c =
0.515, DCM). H NMR (400 MHz, CDCl3): δ = 7.71 [d, J(H,H)
= 8.2 Hz, 2 H], 7.39–7.35 (m, 3 H), 7.31 (s, 1 H), 7.06 [t, J(H,H)
= 7.5 Hz, 2 H], 6.98 [dd, J(H,H) = 8.3, J(H,H) = 2.3 Hz, 2 H],
6.32 (br s, 2 H), 4.34 [d, J(H,H) = 15.6 Hz, 1 H], 4.14 [d, J(H,H)
= 13.8 Hz, 1 H], 3.24 [d, 2J(H,H) = 13.8 Hz, 1 H], 3.11 [d, 2J(H,H)
= 15.5 Hz, 1 H], 0.41 (s, 9 H), 0.31 (s, 9 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 208.4, 180.3, 152.3, 152.2, 138.9, 137.7,
134.0, 133.9, 127.3, 127.3, 127.1, 126.4, 126.1, 125.5, 123.8, 123.6,
114.7, 110.4, 109.5, 76.3, 75.4, 29.8, 26.4, 0.9, 0.5 ppm. IR (film):
3J(H,H) = 4.6 Hz, 1 H], 7.83 (s, 1 H), 7.82 (s, 1 H), 7.72–7.64 (m,
3
2 H), 7.59–7.46 (m, 6 H), 7.31–7.26 (m, 2 H), 7.01 [dd, J(H,H) =
8.4, 4J(H,H) = 0.6 Hz, 1 H], 6.97 [dd, 3J(H,H) = 8.5, 4J(H,H) =
2
2
0.6 Hz, 1 H], 4.01 [d, J(H,H) = 14.5 Hz, 1 H], 3.98 [d, J(H,H) =
2
2
16.1 Hz, 1 H], 3.58 [d, J(H,H) = 14.6 Hz, 1 H], 3.49 [d, J(H,H)
= 16.1 Hz, 1 H], 0.10 (s, 9 H), 0.03 (s, 9 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 208.1, 181.0, 167.0, 166.6, 147.3, 147.1,
139.0, 137.8, 134.2, 134.1, 133.3, 131.1, 130.7, 129.7, 129.7, 129.5,
129.2, 128.7, 127.8, 127.1, 126.9, 126.7, 121.1, 120.7, 113.2, 109.1,
75.7, 74.8, 27.7, 27.2, 0.7, 0.3 ppm. IR (film): ν = 3062.9, 2953.9,
˜
2897.5, 2062.0, 2007.5, 1990.2, 1740.4, 1624.7, 1266.0, 1246.3,
1090.1, 1022.1, 847.1, 711.1 cm–1. HRMS (ESI+): calcd. for
C50H43O8Si2Fe [M + H]+ 883.18537; found 883.187411.
1
3
Complex (R)-1f: Benzyl bromide (53 μL, 0.45 mmol, 6 equiv.) was
added slowly to a stirred solution of (R)-1c (50 mg, 0.07 mmol,
1 equiv.) and K2CO3 (41 mg, 0.30 mmol, 4 equiv.) in DMF
(0.37 mL), and the mixture was stirred at 70 °C overnight. After
this time, the reaction mixture was cooled to room temp. and di-
luted with Et2O (8 mL). The mixture was washed with H2O (3ϫ
5 mL), and the organic phase was dried with Na2SO4. Complex
(R)-1f was obtained as a pale yellow solid after purification by flash
column chromatography (9:1 DCM/hexane), yield 42 mg (70%);
m.p. 155 °C (dec.). [α]3D2 = –20.6 (c = 0.92, DCM). 1H NMR
3
3
4
2
2
ν = 3236.0, 2953.4, 2852.7, 2065.9, 2010.4, 1996.9, 1575.1, 1342.2,
˜
3
1248.2 cm–1. HRMS (ESI+): calcd. for C36H35O6Si2Fe [M + H]+
675.13277; found 675.13152.
(400 MHz, CDCl3): δ = 7.80 [d, J(H,H) = 8.1 Hz, 1 H], 7.71 [d,
3J(H,H) = 8.1 Hz, 1 H], 7.46–7.23 (m, 14 H), 7.11–7.03 (m, 2 H),
6.91–6.84 (m, 2 H), 5.51 [d, 2J(H,H) = 13.5 Hz, 1 H], 5.46 [d,
2J(H,H) = 13.5 Hz, 1 H], 5.26 [d, 2J(H,H) = 11.3 Hz, 1 H], 5.17 [d,
2J(H,H) = 11.3 Hz, 1 H], 4.38 [d, 2J(H,H) = 15.6 Hz, 1 H], 4.29 [d,
2J(H,H) = 13.8 Hz, 1 H], 3.35 [d, 2J(H,H) = 13.8 Hz, 1 H], 3.15 [d,
2J(H,H) = 15.6 Hz, 1 H], 0.32 (s, 9 H), 0.08 (s, 9 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 208.6, 181.1, 154.1, 153.6, 139.0,
137.6, 136.7, 136.1, 133.8, 133.6, 129.1, 128.9, 128.7, 128.5, 128.1,
127.4, 127.4, 127.2, 127.1, 127.1, 127.0, 126.9, 126.9, 126.6, 126.4,
124.3, 124.3, 114.8, 108.7, 108.6, 107.3, 75.8, 75.1, 70.5, 70.1, 26.4,
Complex (R)-1d: Acetyl chloride (32 μL, 0.44 mmol, 3 equiv.) was
added slowly to a stirred solution of (R)-1c (100 mg, 0.15 mmol,
1 equiv.), Et3N (83 μL, 0.59 mmol, 4 equiv.), and DMAP (1.6 mg,
0.015 mmol, 0.1 equiv.) in THF (2 mL), and the mixture was heated
under reflux for 3 h. After this time, the mixture was diluted with
DCM and washed with 0.5 m HCl (2ϫ 5 mL), saturated aqueous
NaHCO3 (5 mL), and brine (5 mL). The organic phase was then
dried with Na2SO4. Complex (R)-1d was obtained as a pale yellow
solid after purification by flash column chromatography (90:10 to
85:15 hexane/AcOEt), yield 103.3 g (92%); m.p. 162–166 °C. [α]2D2
= + 19.37 (c = 0.51, DCM). 1H NMR (400 MHz, CDCl3): δ = 7.90
26.2, 0.8, 0.2 ppm. IR (film): ν = 3063.4, 3034.4, 2953.0, 2899.0,
˜
2060.1, 2004.2, 1987.3, 1757.3, 1620.9, 1596.8, 1246.3, 1105.5,
850.5, 738.1 cm–1. HRMS (ESI+): calcd. for C50H47O6Si2Fe [M +
H]+ 855.22685; found 855.22583.
3
3
[d, J(H,H) = 8.2 Hz, 1 H], 7.87 [d, J(H,H) = 8.2 Hz, 1 H], 7.80
(s, 1 H), 7.73 (s, 1 H), 7.52–7.43 (m, 2 H), 7.25–7.17 (m, 2 H), 6.99
Complex (R)-1g: Methanesulfonyl chloride (17 μL, 0.22 mmol,
3 equiv.) was added slowly to a stirred solution of (R)-1c (50 mg,
0.07 mmol, 1 equiv.), Et3N (41 μL, 0.30 mmol, 4 equiv.), and
DMAP (0.8 mg, 0.007 mmol, 0.1 equiv.) in THF (1 mL), and the
mixture was heated under reflux for 5 h. After this time, the reac-
tion mixture was cooled to room temp., diluted with AcOEt
(5 mL), and washed with 0.5 m HCl (2ϫ 5 mL), saturated aqueous
NaHCO3 (5 mL), and brine (5 mL). The organic phase was dried
with Na2SO4. After concentration, the pure complex (R)-1g was
obtained as a pale yellow solid, yield 40 mg (65%); m.p. 172 °C
(dec.). [α]2D7 = –6.8 (c = 1.4 in DCM). 1H NMR (400 MHz, CDCl3):
δ = 8.12 (s, 1 H), 8.09 (s, 1 H), 7.99 [d, 3J(H,H) = 8.3 Hz, 1 H],
3
3
[d, J(H,H) = 8.4 Hz, 1 H], 6.85 [d, J(H,H) = 8.4 Hz, 1 H], 4.00
[d, 2J(H,H) = 16.0 Hz, 1 H], 3.89 [d, 2J(H,H) = 14.3 Hz, 1 H], 3.36
[d, 2J(H,H) = 14.3 Hz, 1 H], 3.34 [d, 2J(H,H) = 16.0 Hz, 1 H], 2.45
(s, 3 H), 2.39 (s, 3 H), 0.45 (s, 9 H), 0.32 (s, 9 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 208.2, 181.0, 170.1, 169.8, 146.1, 138.8,
137.5, 133.0, 132.9, 130.2, 130.1, 128.7, 127.9, 127.8, 127.5, 127.0,
126.8, 126.7, 126.6, 121.6, 121.1, 112.0, 110.2, 74.9, 74.6, 27.5, 26.6,
22.3, 21.9, 0.9, 0.5 ppm. IR (film): ν = 3062.4, 2953.9, 2923.6,
˜
2903.3, 2852.7, 2062.5, 2007.5, 1989.7, 1768.4, 1624.25, 1189.4,
1155.6, 1087.7, 849.0 cm–1. HRMS (ESI+): calcd. for C50H43O8-
Si2Fe [M + H]+ 759.15395; found 759.15207.
3
3
3
Complex (R)-1e: Benzoyl chloride (26 μL, 0.22 mmol, 3 equiv.) was
added slowly to stirred solution of (R)-1c (50 mg, 0.07 mmol,
7.96 [d, J(H,H) = 8.3 Hz, 1 H], 7.56 [dd, J(H,H) = 8.3, J(H,H)
= 7.0 Hz, 1 H], 7.53 [dd, J(H,H) = 8.3, J(H,H) = 6.9 Hz, 1 H],
3
3
5534
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5526–5536

Catalytic Asymmetric Hydrogenation of Ketones
3
3
7.33 [dd, 3J(H,H) = 8.4, J(H,H) = 7.0 Hz, 1 H], 7.28 [dd, J(H,H)
(ESI+): calcd. for C38H32O10F6S2Si2FeNa [M + Na]+ 961.01332;
found 961.01272.
= 8.5, 3J(H,H) = 6.9 Hz, 1 H], 6.99 [d, 3J(H,H) = 8.4 Hz, 1 H],
6.85 [d, J(H,H) = 8.5 Hz, 1 H], 4.25 [d, J(H,H) = 16.2 Hz, 1 H],
4.15 [d, 2J(H,H) = 14.4 Hz, 1 H], 3.35 [d, 2J(H,H) = 14.4 Hz, 1 H],
3
2
Complex (R)-1j: Complex (R)-1i (100 mg, 0.1 mmol, 1 equiv.),
Pd(OAc)2 (4.5 mg, 0.02 mmol, 0.2 equiv.), PPh3 (10.5 mg,
0.04 mmol, 0.4 equiv.), K3PO4 (63 mg, 0.3 mmol, 3 equiv.), KBr
(26 mg, 0.22 mmol, 2.2 equiv.), and phenylboronic acid (30.5 mg,
0.25 mmol, 2.5 equiv.) were dissolved in dioxane (2.5 mL). The re-
action mixture was heated to 85 °C and stirred overnight. The mix-
ture was diluted with DCM (5 mL), washed with 1 m NaOH
(5 mL), H2O (5 mL), and brine (5 mL), and then dried with
Na2SO4. Complex (R)-1j was obtained as a yellow solid after puri-
fication by flash column chromatography (6:4 to 8:2 DCM/hexane),
yield 69 mg (80%); m.p. 157–158 °C (dec.). [α]2D1 = + 88.3 (c = 0.6,
DCM). 1H NMR (400 MHz, CDCl3): δ = 8.10 (s, 1 H), 8.01 [d,
2
3.33 [d, J(H,H) = 16.2 Hz, 1 H], 3.31 (s, 3 H), 3.29 (s, 3 H), 0.45
(s, 9 H), 0.33 (m, 9 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
208.2, 181.4, 144.4, 143.5, 139.3, 138.0, 132.8, 132.7, 130.5, 130.5,
128.8, 128.5, 128.4, 128.2, 128.0, 127.8, 127.8, 127.7, 126.6, 126.3,
121.9, 121.4, 111.1, 110.1, 75.5, 75.1, 38.8, 38.6, 27.7, 26.7, 0.7,
0.5 ppm. IR (film): ν = 3054.2, 2986.7, 2066.4, 2010.4, 1994.5,
˜
1617.5, 1265.6, 739.1, 705.3 cm–1. HRMS (ESI+): calcd. for
C38H38O10S2Si2FeNa [M + Na]+ 853.06985; found 853.06820.
Complex (R)-1h: p-Toluenesulfonyl chloride (43 mg, 0.22 mmol,
3 equiv.) was added slowly to a stirred solution of (R)-1c (50 mg,
0.07 mmol, 1 equiv.), Et3N (41 μL, 0.03 mmol, 4 equiv.), and
DMAP (0.8 mg, 0.007 mmol, 0.1 equiv.) in THF (1 mL), and the
mixture was heated under reflux overnight. The reaction mixture
was cooled to room temp., diluted with AcOEt (5 mL), and washed
with 0.5 m HCl (2ϫ 5 mL), saturated aqueous NaHCO3 (5 mL),
and brine (5 mL). The organic phase was dried with Na2SO4. After
concentration, the pure complex (R)-1h was obtained as a pale yel-
low solid, yield 63 mg (96%); m.p. 166–168 °C (dec.). [α]2D3 = +
3
3J(H,H) = 8.2 Hz, 1 H], 7.93 [d, J(H,H) = 8.2 Hz, 1 H], 7.90 (s, 1
H), 7.63–7.31 (m, 8 H), 7.26 [dd, 3J(H,H) = 8.5, 3J(H,H) = 7.3 Hz,
3
3
1 H], 7.02 [d, J(H,H) = 8.5 Hz, 1 H], 6.70 [d, J(H,H) = 8.5 Hz,
1 H], 4.27 [d, 2J(H,H) = 14.8 Hz, 1 H], 4.11 [d, 2J(H,H) = 15.8 Hz,
1 H], 3.58 [d, 2J(H,H) = 14.8 Hz, 1 H], 3.50 [d, 2J(H,H) = 15.8 Hz,
1 H], 0.33 (s, 9 H), –0.15 (s, 9 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 208.1, 180.8, 144.9, 141.6, 141.3, 139.4, 136.1, 132.7,
132.5, 132.5, 132.1, 131.1, 130.9, 128.6, 128.3, 128.1, 127.9, 127.6,
127.4, 127.0, 126.4, 125.7, 120.0, 118.9 [q, 1J(C,F) = 321.3 Hz],
111.8, 111.2, 75.9, 75.5, 29.5, 27.5, 0.5, 0.4 ppm. 19F NMR
1
168.6 (c = 1.2, DCM). H NMR (400 MHz, CDCl3): δ = 7.92 (s, 1
H), 7.85 [d, J(H,H) = 8.3 Hz, 1 H], 7.82 [d, J(H,H) = 8.3 Hz, 1
3
3
3
3
H], 7.79 (s, 1 H), 7.70 [d, J(H,H) = 8.0 Hz, 2 H], 7.65 [d, J(H,H)
(282 MHz, CDCl ): δ = –72.1 ppm. IR (film): ν = 3054.7, 2987.2,
˜
3
= 8.0 Hz, 2 H], 7.51 [t, 3J(H,H) = 7.5 Hz, 2 H], 7.29–7.19 (m, 6
2065.4, 2009.5, 1639.7, 1421.8, 1265.6, 744.4, 705.3 cm–1. HRMS
(ESI+): calcd. for C43H37O7F3S1Si2FeNa [M + Na]+ 889.10049;
found 889.10212.
3
3
H), 6.65 [d, J(H,H) = 8.4 Hz, 1 H], 6.54 [d, J(H,H) = 8.5 Hz, 1
2
2
H], 3.93 [d, J(H,H) = 16.1 Hz, 1 H], 3.92 [d, J(H,H) = 14.3 Hz,
1 H], 3.01 [d, 2J(H,H) = 14.3 Hz, 1 H], 2.86 [d, 2J(H,H) = 16.1 Hz,
1 H], 2.40 (s, 3 H), 2.37 (s, 3 H), 0.43 (s, 9 H), 0.27 (s, 9 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 208.0, 181.3, 145.9, 145.9, 145.0,
145.0, 138.8, 137.3, 132.7, 132.5, 132.4, 130.2, 130.1, 130.0, 129.9,
129.3, 128.9, 128.8, 128.5, 128.4, 128.3, 127.4, 127.3, 127.3, 126.2,
126.1, 121.2, 121.2, 111.5, 108.6, 75.3, 74.9, 27.3, 26.4, 21.9, 21.9,
Complex (R)-1l: Diyne 11 (271 mg, 0.50 mmol, 1 equiv.) and
Fe2(CO)9 (455 mg, 1.25 mmol, 2.5 equiv.) were dissolved in toluene
(6 mL), and the mixture was stirred at 90 °C overnight. After cool-
ing to room temperature, the reaction mixture was filtered through
a pad of Celite (rinsed with DCM). The filtrate was concentrated
in vacuo, and the residue was purified by flash column chromatog-
raphy (8:2 hexane/DCM) to afford (R)-1l as a pale yellow solid,
yield 201 mg (57% yield); m.p. 156–158 °C. [α]1D7 = –92.1 (c = 0.4,
DCM). 1H NMR (400 MHz, CDCl3): δ = 7.85 [d, 3J(H,H) =
0.6, 0.6 ppm. IR (film): ν = 3054.2, 2986.7, 2916.8, 2066.4, 2010.9,
˜
1422.2, 1265.6, 895.8, 740.5, 705.3 cm–1. HRMS (ESI+): calcd. for
C50H47O10S2Si2Fe [M + H]+ 983.15069; found 983.14923.
Complex (R)-1i: N-(5-Chloro-2-pyridyl)bis(trifluoromethanesulfon-
imide) (1.2 g, 3.0 mmol, 3 equiv.) was added to a stirred solution
of (R)-1c (670 mg, 1.0 mmol, 1 equiv.), Et3N (550 μL, 4.0 mmol,
4 equiv.), and DMAP (12 mg, 0.1 mmol, 0.1 equiv.) in DCM
(30 mL), and the mixture was stirred at room temp. overnight. The
reaction was diluted with DCM (30 mL) and washed with 0.5 m
HCl (2ϫ 50 mL), 0.5 m NaOH (2ϫ 50 mL), and brine (50 mL).
The organic phase was then dried with Na2SO4. Complex (R)-1i
was obtained as a pale yellow solid after purification by flash col-
umn chromatography (10:1 hexane/AcOEt), yield 882 mg (94%);
3
8.2 Hz, 1 H], 7.80 [d, J(H,H) = 8.2 Hz, 1 H], 7.46–7.30 (m, 5 H),
7.30 (s, 1 H), 7.26 (s, 1 H), 7.21–7.01 (m, 9 H), 6.91 (m, 1 H), 6.81
2
(m, 1 H), 3.97 [d, J(H,H) = 15.2 Hz, 1 H], 3.96 (s, 3 H), 3.86 [d,
2J(H,H) = 14.3 Hz, 1 H], 3.80 (s, 3 H), 3.08 [d, 2J(H,H) = 15.1 Hz,
2
1 H], 2.99 [d, J(H,H) = 14.3 Hz, 1 H] ppm. 13C NMR (100 MHz,
CDCl3): δ = 213.8, 212.2, 205.9, 204.7, 183.1, 167.3, 155.6, 155.1,
148.7, 148.6, 138.6, 138.4, 134.0, 133.8, 132.7, 129.8, 128.6, 128.2,
128.0, 127.5, 127.2, 127.0, 127.0, 127.0, 126.9, 126.6, 126.5, 126.4,
126.4, 126.3, 124.1, 123.9, 105.9, 105.6, 55.1, 54.8, 30.2, 29.3 ppm.
IR (film): ν = 3055.7, 2919.7, 2858.0, 2061.5, 1985.4, 2024.9,
˜
m.p. 142–143 °C (dec.). [α]2D4 = + 43.9 (c = 1.9, DCM). H NMR
1
1599.6, 1451.2, 1111.8, 1025.9 cm–1. HRMS (ESI+): calcd. for
C40H30O2Na [M + Na]+ 733.12972; found 733.13041.
(400 MHz, CDCl3): δ = 8.14 (s, 1 H), 8.12 (s, 1 H), 8.03 [d, 3J(H,H)
3
3
= 8.5 Hz, 1 H], 8.01 [d, J(H,H) = 8.3 Hz, 1 H], 7.62 [t, J(H,H) =
7.5 Hz, 1 H], 7.61 [t, 3J(H,H) = 7.5 Hz, 1 H], 7.40 [t, 3J(H,H) =
3
3
8.2 Hz, 1 H], 7.38 [t, J(H,H) = 8.1 Hz, 1 H], 6.90 [d, J(H,H) =
8.5 Hz, 1 H], 6.84 [d, J(H,H) = 8.5 Hz, 1 H], 4.18 [d, J(H,H) =
Acknowledgments
3
2
2
2
16.2 Hz, 1 H], 4.13 [d, J(H,H) = 14.6 Hz, 1 H], 3.40 [d, J(H,H)
= 14.7 Hz, 1 H], 3.35 [d, 2J(H,H) = 16.2 Hz, 1 H], 0.41 (s, 9 H),
0.31 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 207.9, 181.3,
145.2, 144.9, 139.4, 137.9, 132.7, 132.6, 130.8, 130.7, 128.9, 128.8,
128.8, 128.7, 128.4, 128.3, 127.8, 127.1, 126.2, 126.0, 120.9, 120.8,
The authors thank the European Commission [ITN-EID “RE-
DUCTO” PITN-GA-2012-316371] for financial support and for
predoctoral fellowships (to P. G. and M. R.-C.). L. P. thanks the
Dipartimento di Chimica, Università di Milano, for financial sup-
port (Piano di sviluppo dell’Ateneo-anno 2014-Linea B.1 grants for
young researchers).
119.0 [q, J(C,F) = 324.5 Hz], 118.9 [q, 1J(C,F) = 324.5 Hz], 110.7,
1
108.7, 75.5, 75.5, 27.6, 26.8, 0.5, 0.4 ppm. 19F NMR (282 MHz,
CDCl ): δ = –71.7, –72.7 ppm. IR (film): ν = 3066.7, 2954.9,
˜
3
2925.5, 2903.3, 2852.7, 2065.4, 2011.9, 1993.6, 1629.1, 1427.6,
[1] R. Schlögl, Angew. Chem. Int. Ed. 2003, 42, 2004–2008; Angew.
Chem. 2003, 115, 2050–2055.
1245.8, 1212.5, 1138.3, 915.5, 883.2, 844.7, 822.0 cm–1. HRMS
Eur. J. Org. Chem. 2015, 5526–5536
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5535

L. Pignataro, U. Piarulli, C. Gennari et al.
FULL PAPER
[2] For general reviews on homogeneous iron catalysis, see: a) I.
Bauer, H.-J. Knölker, Chem. Rev. 2015, 115, 3170–3387; b) K.
Gopalaiah, Chem. Rev. 2013, 113, 3248–3296; c) M. Darwish,
M. Wills, Catal. Sci. Technol. 2012, 2, 243–255; d) W. M. Cza-
plik, M. Mayer, J. Cvengrosˇ, A. J. von Wangelin, ChemSus-
Chem 2009, 2, 396–417; e) S. Enthaler, K. Junge, M. Beller,
Angew. Chem. Int. Ed. 2008, 47, 3317–3321; Angew. Chem.
2008, 120, 3363–3367; f) C. Bolm, J. Legros, J. Le Paih, L. Zani,
Chem. Rev. 2004, 104, 6217–6254.
[15] a) S. Moulin, H. Dentel, A. Pagnoux-Ozherelyeva, S. Gaillard,
A. Poater, L. Cavallo, J.-F. Lohier, J.-L. Renaud, Chem. Eur. J.
2013, 19, 17881–17890; b) D. S. Mérel, M. Elie, J.-F. Lohier, S.
Gaillard, J.-L. Renaud, ChemCatChem 2013, 5, 2939–2945; c)
A. Pagnoux-Ozherelyeva, N. Pannetier, M. D. Mbaye, S. Gail-
lard, J.-L. Renaud, Angew. Chem. Int. Ed. 2012, 51, 4976–4980;
Angew. Chem. 2012, 124, 5060–5064; d) J. P. Hopewell, J. E. D.
Martins, T. C. Johnson, J. Godfrey, M. Wills, Org. Biomol.
Chem. 2012, 10, 134–145; e) T.-T. Thai, D. S. Mérel, A. Poater,
S. Gaillard, J.-L. Renaud, Chem. Eur. J. 2015, 21, 7066–7070.
[16] A. Berkessel, S. Reichau, A. von der Höh, N. Leconte, J.-M.
Neudörfl, Organometallics 2011, 30, 3880–3887.
[3] a) R. H. Morris, Acc. Chem. Res. 2015, 48, 1494–1502; b) O. R.
Luca, R. H. Crabtree, Chem. Soc. Rev. 2013, 42, 1440–1459; c)
S. Blanchard, E. Derat, M. Desage-El Murr, L. Fensterbank,
M. Malacria, V. Mouriès-Mansuy, Eur. J. Inorg. Chem. 2012, [17] a) C. P. Casey, H. Guan, J. Am. Chem. Soc. 2007, 129, 5816–
376–389.
5817; b) C. P. Casey, H. Guan, J. Am. Chem. Soc. 2009, 131,
2499–2507.
[18] a) S. Fleischer, S. Zhou, K. Junge, M. Beller, Angew. Chem. Int.
Ed. 2013, 52, 5120–5124; Angew. Chem. 2013, 125, 5224–5228;
b) A. Tlili, J. Schranck, H. Neumann, M. Beller, Chem. Eur. J.
2012, 18, 15935–15939.
[19] a) F. Zhu, L. Zhu-Ge, G. Yang, S. Zhou, ChemSusChem 2015,
8, 609–612; b) S. Fleischer, S. Zhou, S. Werkmeister, K. Junge,
M. Beller, Chem. Eur. J. 2013, 19, 4997–5003; c) S. Zhou, S.
Fleischer, K. Junge, M. Beller, Angew. Chem. Int. Ed. 2011, 50,
5120–5124; Angew. Chem. 2011, 123, 5226–5230.
[20] T. N. Plank, J. L. Drake, D. K. Kim, T. W. Funk, Adv. Synth.
Catal. 2012, 354, 597–601.
[21] a) M. G. Coleman, A. N. Brown, B. A. Bolton, H. Guan, Adv.
Synth. Catal. 2010, 352, 967–970; b) M. K. Thorson, K. L.
Klinkel, J. Wang, T. J. Williams, Eur. J. Inorg. Chem. 2009, 295–
302.
[4] For reviews on Fe-catalyzed reductions, see: a) P. Dupau, M.-
L. Tran Do, S. Gaillard, J.-L. Renaud, Angew. Chem. Int. Ed.
2014, 53, 13004–13006; Angew. Chem. 2014, 126, 13218–13220;
b) G. Bauer, K. A. Kirchner, Angew. Chem. Int. Ed. 2011, 50,
5798–5800; Angew. Chem. 2011, 123, 5918–5920; c) R. H. Mor-
ris, Chem. Soc. Rev. 2009, 38, 2282–2291; d) S. Gaillard, J.-L.
Renaud, ChemSusChem 2008, 1, 505–509.
[5] a) P. J. Chirik, K. Wieghardt, Science 2010, 327, 794–795; b)
S. C. Bart, E. J. Hawrelak, E. Lobkovsky, P. J. Chirik, Organo-
metallics 2005, 24, 5518–5527.
[6] a) R. Langer, M. A. Iron, L. Konstantinovski, Y. Diskin-
Posner, G. Leitus, Y. Ben-David, D. Milstein, Chem. Eur. J.
2012, 18, 7196–7209; b) R. Langer, G. Leitus, Y. Ben-David,
D. Milstein, Angew. Chem. Int. Ed. 2011, 50, 2120–2124; An-
gew. Chem. 2011, 123, 2168–2172; c) P. O. Lagaditis, P. E. Sues,
J. F. Sonnenberg, K. Y. Wan, A. J. Lough, R. H. Morris, J. Am.
Chem. Soc. 2014, 136, 1367–1380; d) Y. Li, S. Yu, X. Wu, J.
Xiao, W. Shen, Z. Dong, J. Gao, J. Am. Chem. Soc. 2014, 136,
4031–4039.
[22] a) A. J. Rawlings, L. J. Diorazio, M. Wills, Org. Lett. 2015, 17,
1086–1089; b) T. Yan, B. L. Feringa, K. Barta, Nat. Commun.
2014, 5, DOI: 10.1038/ncomms6602.
[7] a) T. Zell, Y. Ben-David, D. Milstein, Angew. Chem. Int. Ed.
[23] K. Hopmann, Chem. Eur. J. 2015, 21, 10020–10030.
2014, 53, 4685–4689; Angew. Chem. 2014, 126, 4773–4777; b) [24] P. Gajewski, M. Renom-Carrasco, S. Vailati Facchini, L. Pig-
S. Werkmeister, K. Junge, B. Wendt, E. Alberico, H. Jiao, W.
Baumann, H. Junge, F. Gallou, M. Beller, Angew. Chem. Int.
Ed. 2014, 53, 8722–8726; Angew. Chem. 2014, 126, 8867–8871.
[8] R. Langer, Y. Diskin-Posner, G. Leitus, L. J. W. Shimon, Y.
Ben-David, D. Milstein, Angew. Chem. Int. Ed. 2011, 50, 9948–
9952; Angew. Chem. 2011, 123, 10122.
[9] a) R. Bigler, R. Huber, A. Mezzetti, Angew. Chem. Int. Ed.
2015, 54, 5171–5174; Angew. Chem. 2015, 127, 5260; b) R. Bi-
gler, A. Mezzetti, Org. Lett. 2014, 16, 6460–6463; c) W. Zuo,
A. J. Lough, Y. F. Li, R. H. Morris, Science 2013, 342, 1080–
1083; d) S. Yu, W. Shen, Y. Li, Z. Dong, Y. Xu, Q. Li, J. Zhang,
J. Gao, Adv. Synth. Catal. 2012, 354, 818–822; e) P. O. Lagad-
nataro, L. Lefort, J. G. de Vries, R. Ferraccioli, A. Forni, U.
Piarulli, C. Gennari, Eur. J. Org. Chem. 2015, 1887–1893.
[25] The importance of 3,3Ј-substituents for an efficient transfer of
the stereochemical information has been reported for many BI-
NOL-derived catalytic systems: a) see ref.[26]; b) D. Kampen,
C. Reisinger, B. List, Top. Curr. Chem. 2009, 291, 1–37; c) M.
Terada, Chem. Commun. 2008, 4097–4112.
[26] a) B. Ye, N. Cramer, Angew. Chem. Int. Ed. 2014, 53, 7896–
7899; Angew. Chem. 2014, 126, 8030–8033; b) B. Ye, N. Cramer,
J. Am. Chem. Soc. 2013, 135, 636–639.
[27] D. L. Comins, A. Dehghani, Tetrahedron Lett. 1992, 33, 6299–
6302.
itis, A. J. Lough, R. H. Morris, J. Am. Chem. Soc. 2011, 133, [28] T. Ohe, N. Miyaura, A. Suzuki, J. Org. Chem. 1993, 58, 2201–
9662–9665; f) P. E. Sues, A. J. Lough, R. H. Morris, Organome- 2208.
tallics 2011, 30, 4418–4431; g) P. O. Lagaditis, A. J. Lough, [29] H.-J. Knölker, E. Baum, H. Goesmann, R. Klauss, Angew.
R. H. Morris, Inorg. Chem. 2010, 49, 10057–10066; h) A. Naik,
T. Maji, O. Reiser, Chem. Commun. 2010, 46, 4475–4477.
[10] S. Zhou, S. Fleischer, K. Junge, S. Das, D. Addis, M. Beller,
Angew. Chem. Int. Ed. 2010, 49, 8121–8125; Angew. Chem.
2010, 122, 8298–8302.
[11] For the first report, see: G. N. Schrauzer, J. Am. Chem. Soc.
1959, 81, 5307–5310.
[12] For a recent review on (cyclopentadienone)iron complexes, see:
A. Quintard, J. Rodriguez, Angew. Chem. Int. Ed. 2014, 53,
4044–4055; Angew. Chem. 2014, 126, 4124–4136.
[13] B. L. Conley, M. K. Pennington-Boggio, E. Boz, T. J. Williams,
Chem. Rev. 2010, 110, 2294–2312.
[14] X. Lu, Y. Zhang, P. Yun, M. Zhang, T. Li, Org. Biomol. Chem.
2013, 11, 5264–5277.
Chem. Int. Ed. 1999, 38, 2064–2066; Angew. Chem. 1999, 111,
2196–2199.
[30] A. F. Littke, C. Dai, G. C. Fu, J. Am. Chem. Soc. 2000, 122,
4020–4028.
[31] T. Watanabe, N. Miyaura, A. Suzuki, Synlett 1992, 207–210.
[32] The syntheses of (cyclopentadienone)iron complexes by the re-
actions of cyclopentadienones with Fe2(CO)9 or Fe(CO)5 are
known, see: a) H. K. Gupta, N. Rampersad, M. Stradiotto,
M. J. McGlinchey, Organometallics 2000, 19, 184–191; b) E.
Weiss, W. Hübel, J. Inorg. Nucl. Chem. 1959, 11, 42–55.
[33] W. C. Still, M. Kahn, A. Mitra, J. Org. Chem. 1978, 43, 2923–
2925.
Received: June 16, 2015
Published Online: July 23, 2015
5536
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 5526–5536