Transition metal complexes of fesulphos ligands in enantioselective catalytic transformations

Article abstract of DOI:10.1080/10426500590911458

Metal complexes of 1-phosphino-2-sulfenylferrocene (fesulphos ligands) act as highly efficient catalysts in Pd-catalyzed desymmetrization of meso heterobicyclic alkenes and in Cu-catalyzed formal aza Diels-Alder reaction of Danishefsky diene to N-sulfonyl

Full text of DOI:10.1080/10426500590911458

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Phosphorus, Sulfur, and Silicon
and the Related Elements
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Transition Metal Complexes
of Fesulphos Ligands in
Enantioselective Catalytic
Transformations
Juan Carlos Carretero a , Ramón Gómez Arrayás a
Olga García Mancheño a & Silvia Cabrera a
,
a Departamento de Química Orgánica, Facultad de
Ciencias, Universidad Autónoma de Madrid , Madrid,
Spain
Published online: 16 Aug 2006.
To cite this article: Juan Carlos Carretero , Ramón Gómez Arrayás , Olga García
Mancheño & Silvia Cabrera (2005) Transition Metal Complexes of Fesulphos Ligands in
Enantioselective Catalytic Transformations, Phosphorus, Sulfur, and Silicon and the
Related Elements, 180:5-6, 1259-1265, DOI: 10.1080/10426500590911458
To link to this article: http://dx.doi.org/10.1080/10426500590911458
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Phosphorus, Sulfur, and Silicon, 180:1259–1265, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500590911458
Transition Metal Complexes of Fesulphos Ligands
in Enantioselective Catalytic Transformations
´
´
´
´
˜
Ramon Gomez Arrayas
Olga Garcıa Mancheno
Silvia Cabrera
Juan Carlos Carretero
Departamento de Qu´ımica Orga´nica, Facultad de Ciencias, Universidad
Auto´noma de Madrid, Madrid, Spain
Metal complexes of 1-phosphino-2-sulfenylferrocene (fesulphos ligands) act as
highly efficient catalysts in Pd-catalyzed desymmetrization of meso heterobicyclic
alkenes and in Cu-catalyzed formal aza Diels–Alder reaction of Danishefsky diene
to N-sulfonyl imines.
Keywords Aza Diels–Alder; planar chirality; ring-opening; sulfonyl imines; sulfur
ligands
INTRODUCTION
Thioether-based chiral ligands hold great promise in enantioselective
catalysis because the sulfur atom becomes stereogenic upon coordina-
tion to a metal, which imposes a unique asymmetric environment next
to the reactive metal center. We have recently developed a novel family
of P,S-bidentate ligands possessing planar chirality as the only element
of asymmetry: Fesulphos 1 (1-phosphino-2-sulfenylferrocenes).1 The
modular approach to their synthesis enables easy fine-tuning of their
asymmetric performance by simple modification of the electronic and
steric properties of the groups attached to phosphorus and sulfur. Lig-
ands 1 proved to be highly efficient in the Pd-catalyzed allylic substitu-
tions of 1,3-diphenylpropenyl acetate (96–99.5% ee).1 Described herein
Received July 9, 2004; accepted October 5, 2004.
Financial support by MEC (BQU2003-0508) is gratefully acknowledged. R. G. A.
thanks the MEC for a Ramon y Cajal contract. O. G. M. and S. C. thank MEC and UAM,
respectively, for predoctoral fellowships.
Address correspondence to Juan Carlos Carretero, Departamento de Qu´ımica
Orga´nica, Facultad de Ciencias, Universidad Auto´noma de Madrid, Cantoblanco, 28049
Madrid, Spain. E-mail: juancarlos.carretero@uam.es
1259

1260
R. G. Arraya´s et al.
is the behavior of metal complexes of these ligands as chiral catalysts
in other asymmetric transformations such as the Pd-catalyzed ring-
opening reaction of meso bicyclic alkenes,2 and the Cu-catalyzed aza
Diels–Alder cycloaddition of electron-rich dienes to N-sulfonyl imines.3
RESULTS
Cationic Palladium Complexes of Fesulphos
in the Asymmetric Ring-Opening Reaction
of Meso Heterobicyclic Alkenes
The Pd-catalyzed enantioselective ring opening of meso oxabicyclic
alkenes with dialkylzinc reagents is a powerful C C bond-forming re-
action recently reported by Lautens.4 Inspired by mechanistic stud-
ies evidencing enantioselective carbopalladation of the alkene with
cationic alkyl palladium species [L2PdR]+ as the key step, we en-
visioned that the cationic methylpalladium complexes of Fesulphos
[(1)PdMe]+ could function as very active catalysts in this reaction.
Scheme 1 shows the preparation of such cationic complexes. Treatment
of 1 with PdCl2(CH3CN)2 afforded in very high yield the correspond-
ing complexes [(1)PdCl2] as single epimers at sulfur. Interestingly, the
transmetallation reaction of these complexes with Me2Zn was com-
pletely stereoselective, affording a single complex [(1)Pd(Cl)(Me)] in 70–
95% yield. The cis arrangement of the methyl group and the phosphine
was unequivocally established by X-ray crystal diffraction analysis of
the complex [(1a)Pd(Cl)(Me)].
SCHEME 1 a) PdCl2(CH3CN)2, CH2Cl2, rt; b) Me2Zn (1.5 equiv.), CH2Cl2, rt;
c) AgPF6 or NaBArF4 , PhCN, CH2Cl2, rt.
The ring-opening reaction of oxabenzonorbornadiene with Me2Zn in
the presence of a 5 mol% of neutral palladium complexes [(1a)PdCl2]
and [(1a)Pd(Cl)(Me)] in toluene at room temperature (rt) led to about
80% conversion after 24 h, affording the ring-opened product in 81–85%
ee (Scheme 2 and Table I). Remarkably, a complete conversion was ob-
served within 10 min when 5 mol% of the air-stable cationic complex

Fesulphos Ligands
1261
TABLE I
Catalyst(× mol%)
Time
Yield (%) ee (%)
1a·PdCl2 (5.0)
24 h
24 h
10 min
5 h
80
75
86
88
81
85
78
97
1a·Pd(Cl)(Me) (5.0)
[1a·Pd(Me)(NCPh)] + NaBArF4 (5.0)
[1a·Pd(Me)(NCPh)] + NaBArF4 (0.2)
[(1a)Pd(Me)(PhCN)]BArF4 [ArF = 3,5-bis(trifluoromethyl)phenyl] was
used (78% ee). To fine-tune the reactivity and enantioselectivity of the
process we next studied the effect of the substitution at the phospho-
rus atom (complexes of ligands 1b–e), the complex of the electronically
rich dicyclohexyl phosphane 1e providing best results. In fact, the com-
bination of [(1e)Pd(Cl)(Me)] +NaB(ArF)4 proved to be so effective that
catalyst loading as low as 0.2 mol% was sufficient to reach quantitative
conversion within 5 h at −25◦C, which afforded alcohol 2a in 88% yield
with 97% ee.
SCHEME 2
Figure 1 highlights the scope of the process. Complete conversions
within 10–30 min, good chemical yields (61–98%), and excellent enan-
tioselectivities (94–99% ee, HPLC) were obtained in the ring opening
of a variety of substituted meso oxabenzonorbornadienes with both
Me2Zn and Et2Zn in DCE at room temperature by using 0.5 mol%
[(1e)Pd(Cl)(Me)] in combination with NaB(ArF)4 (0.5 mol%) as catalyst.
The efficiency of these highly active catalysts toward much less re-
active bicyclic substrates was also studied (Scheme 3). Thus, 1 mol%
FIGURE 1

1262
R. G. Arraya´s et al.
SCHEME 3
of both [(1a)Pd(Me)]+ and [(1e)Pd(Me)]+ induced the ring-opening re-
action of nonaromatic [2.2.1]-oxabicyclic alkene with Me2Zn in 3 h at
rt, providing the corresponding cyclohexenol in 96–97% ee. On the
other hand, a 5 mol% of the complex [(1a)Pd(Me)(PhCN)]+(PF6)− cat-
alyzed the opening of the N-tosyl azabenzonorbornadiene with Me2Zn
in 30 min at room temperature, the corresponding (R,R)-2-methyl-1-
tosylaminodihydronaphthalene being obtained with virtually complete
enantiocontrol (>99% ee).
The X-ray structure of palladium complexes shown in Scheme 1 sug-
gests that the high asymmetric induction displayed by these catalysts
relies on the strong trans effect of the phosphane moiety that acts in
combination with the sterically demanding environment imposed by
the stereogenic sulfur atom directly bonded to the palladium.
Copper Complexes of Fesulphos as Chiral Lewis
Acids for Enantioselective Aza Diels–Alder Reactions
of N-Sulfonyl Imines
The catalytic enantioselective aza Diels–Alder reaction of electron-rich
dienes with aldimines5 is conceptually an extremely powerful strategy
for the construction of dihydropyridones, which are key intermediates
in the synthesis of biologically active alkaloids.6 Initially, we performed
TABLE II
4
Cu salt
Yield (%)
ee (%)
Cu(MeCN)4ClO4
Cu(MeCN)4PF6
CuOTf
83
72
80
74
77
76

Fesulphos Ligands
1263
the reaction of Danishefsky’s diene with the N-tosylimine of benzalde-
hyde in the presence of a 10 mol% of ligand 1a and Cu(CH3CN)4ClO4
in CH2Cl2 at rt. Complete conversion was observed within 5 h to afford
the Mannich-type addition product 3, which was readily transformed
into the cycloadduct 4 upon addition of TFA to the reaction mixture
(Scheme 4 and Table II). Similar results were obtained with other Cu(I)
salts.
SCHEME 4
We turned our attention towards the isolation and structural study of
Cu(I) complexes of Fesulphos ligands, whose preparation was achieved
by simple combination of equimolar amounts of ligands 1a–e and CuX
(X = Cl, Br) in THF/MeOH (Scheme 5). The tetrahedral coordination at
copper and the absolute (R) configuration at sulfur of the single epimer
obtained in all cases were unambiguously established by X-ray analysis
of 5a.
SCHEME 5
The evaluation of this set of copper complexes (5.1 mol%), combined
with AgClO4 (10 mol%) as chiral catalysts in the model aza Diels–Alder
reaction, led us to find that both reactivity and enantioselectivity were
deeply influenced by the substitution at phosphorus. Complex 6d, hav-
ing the bulky α-naphthylphosphine moiety, exhibited highest values of
reactivity and asymmetric induction, affording (R)-4 in 87% yield and
97% ee at −20◦C (90% yield and 93% ee at room temperature).

1264
R. G. Arraya´s et al.
TABLE III
R
Yield (%)a
ee (%)b
Ph
o-Tol
90
82
78
76
39
85
66
65c
93 (97)c
93
(p-F)C6H4
(p-OMe)C6H4
(p-NMe2)C6H4
2-Naph
PhCH CH
n-Pr
88 (93)c
91
93
86 (93)c
83 (96)c
73c (82)d
aIsolated yield; bDetermined by HPLCs; cAT-20◦C; dAt-78◦C.
With optimized catalyst 6d in hand, the scope of the reaction was
next explored with a variety of other N-sulfonyl imines (Scheme 6 and
Table III). A high degree of stereochemical fidelity was observed with
SCHEME 6
a number of electronically varied aromatic imines (entries 1–6, 86–
93% ee at rt; 93–97% ee at −20◦C). It is also noteworthy that the high
reactivity and enantioselectivity displayed by the tosyl imine of cin-
namaldehyde, the reaction being complete within 1 h at –20◦C to afford
the cycloadduct with 82% yield and 96% ee. As far as we know, this
is the first example of a catalytic enantioselective aza Diels–Alder re-
action of α,β-unsaturated imino dienophiles. The applicability of this
protocol to aldimines of enolizable aliphatic aldehydes, a kind of het-
erodienophiles scarcely studied in this reaction, was demonstrated with
the tosylimine of butyraldehyde, which reacted in 30 min at −20◦C to
provide the corresponding dihydropyridone in 65% yield and 73% ee
(82% ee at −78◦C).
Finally, from a practical point of view, it is important to note that
these N-sulfonyl dihydropyridones are crystalline solids, giving rise to
enantiopure samples (>99.5% ee) upon a single recrystallization.
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Fesulphos Ligands
1265
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