1
Asymme ic hyd ogena ion eac ions wi h Rh and Ru complexes bea ing
phosphine-phosphi es wi h an oxyme hylene backbone
Pa yk Kleman, Mónica Vaque o, Inmaculada A ibas, And és Suá ez, Eleu e io
Ál a ez and An onio Pizzano*
Ins i u o de In es igaciones Químicas,
Consejo Supe io de In es igaciones Cien í icas and Uni e sidad de Se illa,
c/ Amé ico Vespucio 49, Isla de la Ca uja, 41092 Se illa (Spain).
Abs ac
Phosphine-phosphi es 3a and 3b, de i ed om diphenylhyd oxyme hyl phosphine ha e
been p epa ed. F om hese ligands [Rh(COD)(3a)]BF
4
(5a) and RuCl
2
(3b)[(S,S)-DPEN]
(6b, DPEN = 1,2-diphenyle hylenediamine) we e syn hesized and hei s uc u e
de e mined by X- ay di ac ion. Ligands 3 a e cha ac e ized by a small bi e angle o
83º. In addi ion, 5a led o an ac i e ca alys o he hyd ogena ion o ole ins, gi ing
enan ioselec i i ies up o 96 % ee. Likewise, compound 6b showed a good ac i i y and
enan ioselec i i y in he hyd ogena ion o N-1-phenyl e hylidene aniline and comple ed
a eac ion a S/C = 500 in 24 h wi h a 83 % ee.
* Co esponding au ho : phone: 34+954489556; e-mail: [email p o ec ed].
2
In oduc ion
Chi al phosphine-phosphi e ligands ha e become in an impo an class o
ligands o asymme ic ca alysis.
1
F om he ini ial applica ion o BINAPHOS in he
asymme ic hyd o o myla ion o ole ins,
2
a b oad ange o ligands ha e been p epa ed
and es ed in di e se ca aly ic eac ions, exhibi ing a wide scope.
3-9
Rega ding
hyd ogena ion, he applica ion o phosphine-phosphi es has led o e icien Rh,
10
I
11
o
Ru
12
ca alys s o he educ ion o C=C and C=N bonds, sui able no only o es
subs a es, bu o mo e syn he ically ele an ones as well.
13
Conside ing he a he unlimi ed possibili ies o ligand uning ha phosphine-
phosphi es allow, he s udy o he in luence o main ligand ea u es in a ca aly ic
eac ion has high alue on guiding he ca alys op imiza ion p ocess. In ecen yea s we
ha e p epa ed a lib a y o phosphine-phosphi es which possess a C-C-O backbone as a
common ea u e. Thus, ligands 1 and 2 a e cha ac e ized by an oxyphenylene and an
oxye hylene b idge subs i uen s, espec i ely. A his espec , he na u e o he backbone
in hese phosphine-phosphi es g ea ly in luences he con o ma ional mobili y o he
coo dina ed ligand and he o ien a ion o he phosphine subs i uen s, which may ha e a
p o ound in luence on he ca alysis.
14
In connec ion wi h his, Bakos and cowo ke s
ha e shown an impo an in luence o he leng h o he backbone in hodium ca alyzed
ole in hyd ogena ion using BINOL and H
8
-BINOL based ligands wi h oxyme hylene o
oxybu ylene b idges.
15
On he o he hand, we ha e also obse ed ha he use o bulkie ,
e c-bu yl based phosphi e agmen s, has a p o ound e ec on enan ioselec i i y in
di e se ole in and imine hyd ogena ions.
10g, 12b
Upon hese conside a ions and as a
complemen o ou p e ious wo k wi h ligands o ypes 1 and 2, we desc ibe he ein a
3
s udy dealing wi h oxyme hylene b idged ligands 3. Mo eo e , hese compounds a e
pa icula ly appealing om a syn he ic pe spec i e, as he co esponding
hyd oxyphosphine, which is he mos demanding componen in he syn hesis o
phosphine-phosphi es, can easily be p epa ed in one s ep and high yield om
diphenylphosphine and o maldehyde.
16
Thus, his con ibu ion includes he syn hesis
and pe o mance o ligands 3 in se e al ep esen a i e enan ioselec i e hyd ogena ion
eac ions, while complemen a y s uc u al in o ma ion has been ob ained by an X- ay
c ys allog aphy s udy on hei coo dina ion complexes.
Figu e 1. S uc u e o phosphine-phosphi e ligands.
Resul s and Discussion
Ini ially, phosphine-phosphi es 3a and 3b we e ob ained by condensa ion o
diphenylhyd oxyme hylphosphine wi h chlo ophosphi es 4a and 4b, espec i ely
(Scheme 1). These compounds ha e been cha ac e ized by he usual analy ic and
4
spec oscopic echniques and he da a ob ained a e in acco d wi h he p oposed
s uc u es. Among he cha ac e iza ion da a i should be highligh ed ha ligands 3 a e
cha ac e ized by wo double s in he
31
P{
1
H} NMR wi h a small
2
J
PP
coupling cons an
o ca. 4 Hz.
NE 3
OH
PPh2O
Ph2P
3
Cl PO
O
4
a:PO
O
=PO
O
B
u
Bu
b:PO
O
=PO
O
Bu
Bu
Bu
Bu
+PO
O
Scheme 1. Syn hesis o oxyme hylene b idged ligands 3.
Resea ch om ou labo a o y has shown ha chi al phosphine-phosphi es ha e
b oad applica ion in he hodium ca alyzed hyd ogena ion o ole ins, while achi al
coun e pa s also ha e in e es in he hyd ogena ion o imines ca alyzed by u henium
ca alys s bea ing a chi al diamine as an ancilla y ligand.
12b
Upon hese p eceden s
ca alys p ecu so s o o mula [Rh(COD)(3a)]BF
4
(5a) and RuCl
2
(4a)[(S,S)-DPEN]
(6b) we e p epa ed (Scheme 2).
5
Scheme 2. P epa a ion o complexes 5a and 6b.
Wi h he in en ion o gain in o ma ion abou he s uc u e o coo dina ed ligands
3, complexes 5a and 6b ha e been cha ac e ized by X- ay di ac ion. Rh compound 5a
shows a squa e-plana s uc u e (Figu e 2). A i s in e es ing obse a ion de i es om
he coo dina ion o he diole in. Calcula ion o dis ance om he hodium a om o he
ole in bond cen oids gi e alues o 2.209 and 2.171 Å, e lec ing he expec ed highe
ans in luence o he phosphi e agmen .
17
In addi ion, hese dis ances a e ela i ely
high conside ing he ange o diphosphine de i a i es, which ypically oscilla es
be ween 2.10 and 2.17 Å.
18
In con as o he ypical clock/coun e clockwise u n
obse ed o COD de i a i es o chi al diphosphines minimizing s e ic
in e ac ions,
18
coo dina ion o COD in 5a shows a displacemen o bo h ole in cen oids
abo e he coo dina ion plane. Thus C(39) and C(42) ole ínic ca bons nea ly lie in he
equa o ial plane. This s uc u al ea u e, enabled by he C
1
symme y o he chi al
ligand, as well as he ela i ely long Rh-ole in bonds can be a ibu ed o he high s e ic
encumb ance p oduced by bo h phospho us unc ionali ies o he phosphine-phosphi e
ligand, pa icula ly below he coo dina ion plane by he a yl ing o he biphenyl
de ined by C(11) and he edge o ien ed phenyl sub i uen de ined by C(26). Mo eo e ,
as obse ed be o e in s uc u es o ligands 1a and 2a, he PPh
2
agmen displays a
6
ypical p opelle -like a angemen o he phenyl subs i uen s wi h ha abo e he
coo dina ion plane in a pseudoaxial posi ion and he phenyl below he plane in a
pseudoequa o ial posi ion. Mos in e es ingly, he s uc u e is cha ac e ized by a bi e
angle o 82.6 deg ees (Figu e 2b), which is in he ange obse ed o e hane b idged
diphosphines, while subs an ially smalle han hose obse ed o complexes o ligands
1 and 2. The la e ypically ange a ound 90 deg ees (e.g. 90.9º in [I (COD)(1b)]BF
4
and 88.6 in Rh(Cl)(CO)(2a)). In addi ion, he adop ion o he i e membe ed
me alacycle p oduces alues o O-P-Rh and C-P-Rh angles o 114.3 and 106.6º. These
alues a e smalle han hose ound o he six membe ed me alacycle o he
a o emen ioned I compound, which show alues o 115 and 121º, espec i ely.
Compa ison wi h i e membe ed me alacycles de ined by diphosphines indica es
simila alues o he angles wi h he excep ion o he P(1)-O(3)-C(25) angle o 116.5º
(Figu e 3a), which is wide han he ypical alue o 107º o P-C-C agmen s in
diphosphines.
Figu e 2. (a) ORTEP iew o complex 5a.
7
On he o he hand, he Ru complex shows a dis o ed oc ahed al s uc u e wi h a
cis a angemen o he chlo o ligands. Thus, he phosphi e and one o he chlo o ligands
occupy he axial posi ions while he amine ni ogens, he emaining chlo o and he
phosphine occupy he equa o ial plane (Figu e 4). As men ioned in he s uc u e o 5a,
6b also displays a na ow bi e angle o 82.1 deg ees (Figu e 3b). This con as s, o
ins ance, wi h he alue o e hane b idged RuCl
2
(1a)[(R,R)-DPEN] which displays a
bi e angle o 92.3 deg ees. In addi ion, he s uc u e exhibi s a signi ican ans
in luence o he phosphi e g oup as he Ru-Cl(1) dis ance is app eciable longe han ha
Ru-Cl(2) one (2.461 and 2.404 Å, espec i ely). I is no iceable ha despi e complexes
5a and 6b ha e di e en na u e, he pa ame e s o he me alacycle a e e y simila .
Figu e 3. Angles (deg ees) ound in he me alacycles o med by 5a (a) and 6b (b).
8
Figu e 4. ORTEP iew o complex 6b.
Mo eo e , complexes 5a and 6b show in he
31
P{
1
H} NMR spec a
2
J
PP
coupling
cons an s, o 39 Hz and 47 Hz, espec i ely. These alues a e signi ican ly lowe han
cons an s ound in complexes wi h a longe backbone. Fo compa ison i can be ecalled
ha his coupling cons an amoun s 61 Hz in [Rh(COD)(1a)]BF
410g
and 69 Hz in
RuCl
2
(1a)[(S,S)-DPEN].
12b
We we e nex in e es ed in compa ing he pe o mance o ca alys p ecu so 5a
wi h hose based in phosphine-phosphi e ligands 1 in he asymme ic hyd ogena ion o
se e al ep esen a i e ole ins (Figu e 5). Fi s , complex 5a showed ull con e sion and
a 91 % ee in he hyd ogena ion o MAA (7b) unde mild condi ions (Table 1). In he
case o MAC (7a) he eac ion was slowe unde hese condi ions (70 % con e sion) bu
a highe enan ioselec i i y o 96 % ee was obse ed. In addi ion, he hyd ogena ion o
dime hyl i acona e also p oceeded smoo hly wi h a good enan ioselec i i y o 89 % ee.
9
Compa ison o hese esul s wi h hose ob ained wi h he analogous ca alys o longe
ligand backbone 1a shows ha he p oximi y be ween he wo phospho us
unc ionali ies in ligand 3a is de imen al o hese hyd ogena ions, since in he h ee
cases he ca alys bea ing ligand 1a p o ided highe enan ioselec i i ies (99 % ee) o
he h ee ole ins. In addi ion, we we e in e es ed on in es iga ing he in luence o he
size o he phosphi e agmen in oxyme hylene b idged ligands. A his ega d, i
should be men ioned ha li e a u e da a indica es ha a ca alys bea ing a BINOL based
ligand (3c), showed a 64 % ee in he hyd ogena ion o MAC.
15
Fo he sake o
comple ion we ha e gene a ed complex [Rh(COD)(3c)]BF
4
in si u and pe o med he
hyd ogena ions o MAA and dime hyl i acona e unde ou s anda d condi ions. Bo h
eac ions showed ull con e sion and enan ioselec i i ies o 54 and 87 % ee,
espec i ely (en ies 4,5). O e all, hese alues indica e a be e pe o mance o he
ca alys bea ing he bulkie phosphi e in he hyd ogena ion o he enamides, while
simila esul s o ca alys s based on 3a and 3c we e ob ained in he case o
dime hyli acona e. Howe e , he bulky phosphi e g oup along wi h he sho backbone
should ende a a he conges ed me al cen e ha should be de imen al o ca alys
ac i i y, as shown in he uncomple ed hyd ogena ion o MAC.
16
144.7 (d, J
CP
= 14 Hz; Cq a om); Elem. Anal. Calcd o C
45
H
56
BF
4
O
3
P
2
Rh (%): C,
60.28; H, 6.30. Found: C, 60.05; H, 6.47
[RuCl
2
(3b)[(S,S)-DPEN)] (6b). A solu ion o Ru(COD)(η
3
-2-MeC
3
H
4
)
2
(0.072
g, 0.20 mmol) and 3b (0.078 g, 0.12 mmol) in n-hexane (5 mL) was hea ed unde e lux
o 5h. The mix u e was e apo a ed unde educed p essu e and he esidue dissol ed in
CH
2
Cl
2
(3 mL). The solu ion was added d opwise o e a solu ion o (S,S)-DPEN (0.043
g, 0.20 mmol) and HCl (8 mL, 0.05 M in E
2
O) cooled a -20 ºC. The esul ing mix u e
was s i ed o 30 min a oom empe a u e, e apo a ed unde acuum and he esidue
was pu i ied by column ch oma og aphy using a cyclohexane/E
2
O 1:1 mix u e. Yellow
solid (0.057 g, 25 %).
1
H NMR (CD
2
Cl
2
, 500 MHz): δ 1.06 (s, 9H, CMe
3
), 1.12 (s, 9H,
CMe
3
), 1.30 (s, 9H, CMe
3
), 1.37 (s, 9H, CMe
3
), 2.99 (m, 1H, NHH), 3.16 (m, 1H,
NHH), 3.96 (m, 1H, NHH), 4.11 (m, 1H, NHH), 4.26 (ddd, J
HH
= 11.8 Hz, J
HH
= 4.5
Hz, J
HH
= 4.5 Hz, 1H, CHNH
2
), 4.40 (ddd, J
HH
= 11.8 Hz, J
HH
= 4.3 Hz, J
HH
= 4.3 Hz,
1H, CHNH
2
), 4.94 (m, 2H, PCH
2
), 6.95 (m, 3H, 3 H a om), 7.07 (m, 4H, 4 H a om),
7.13 (m, 6H, 6 H a om), 7.31 (m, 3H, 3 H a om), 7.36 (m, 4H, 4 H a om), 7.72 (m, 4H,
4 H a om);
31
P NMR (CD
2
Cl
2
, 202.5 MHz,): δ 69.7 (d, PC, J
PP
= 47 Hz), 171.9 (d, PO);
13
C NMR (CD
2
Cl
2
, 125 MHz): δ 30.2 (CMe
3
), 31.4 (CMe
3
), 31.5 (CMe
3
), 31.8 (CMe
3
),
32.2 (CMe
3
), 34.7 (d, J
CP
= 4 Hz, CMe
3
), 36.6 (CMe
3
), 36.8 (CMe
3
), 63.3 (s, 2 CH,
CHNH
2
), 67.8 (dd, J
CP
=34 Hz, J = 14 Hz, PCH
2
), 125.9 (CH a om), 126.2 (CH a om),
127.4 (CH a om), 127.7 (CH a om), 127.8 (2 CH a om), 127.9 (2 CH a om), 128.5 (2
CH a om), 128.6 (CH a om), 128.6 (CH a om), 128.7 (2 CH a om), 129.3 (2 CH a om),
129.5 (2 CH a om), 130.3 (2 CH a om), 131.1 (C
q
a om), 131.8 (d, J
CP
= 3 Hz, C
q
a om), 133.6 (CH a om), 133.7 (2 CH a om), 133.8 (CH a om), 134.7 (C
q
a om), 134.8
(C
q
a om), 135.0 (C
q
a om), 135.1 (C
q
a om), 140.1 (C
q
a om), 140.2 (2 C
q
a om), 140.5
(C
q
a om), 146.6 (d, J
CP
= 38 Hz, C
q
a om), 146.7 (d, J
CP
= 33 Hz, C
q
a om). Elem.
17
Anal. Calcd o C
55
H
68
Cl
2
N
2
O
3
P
2
Ru (%): C, 63.58; H, 6.60; N, 2.70. Found: C, 63.51;
H, 6.81; N, 2.76.
P ocedu e o he asymme ic hyd ogena ion o ole ins 7a-7c. In a glo ebox,
a solu ion o 7b (5.3 mg, 0.037 mmol) and 5a (0.33 mg, 0.35 µmol) in CH
2
Cl
2
(2.0 mL)
was placed in a HEL CAT-18 eac o . The eac o was pu ged wi h hyd ogen and
inally p essu ized a 4 ba . The eac ion was s i ed o 24 h. Then, he eac o was
e acua ed and he esul ing solu ion e apo a ed unde acuum. The emaining esidue
was analyzed by
1
H NMR o de e mine con e sion. Then i was b ough o d yness, and
dissol ed in a i-P OH/n-hexane 1:9 mix u e and passed h ough a sho pad o silica o
emo e ca alys impu i ies.The solu ion ob ained was e apo a ed and he esidue
ob ained was analyzed by chi al ch oma og aphy o de e mine enan iome ic excess as
ollows: N-ace yl phenylalanine me hyl es e (8a): HPLC, n-hexane:i-P OH 90:10;
1.0 mL/min,
1
(R) = 14.5 min,
2
(S) = 19.1 min; N-ace yl alanine me hyl es e (8b):
GC, Supelco β-DEX 225, 15 psi He, 150
o
C,
1
(S) = 6.9 min,
2
(R) = 7.2 min; dime hyl
2-me hylsuccina e (8c): GC, Supelco γ-DEX 225, 15 psi He, 70 ºC (5 min), 10 ºC/min
up o 130 ºC,
1
(S) = 12.6 min,
2
(R) = 12.7 min.
P ocedu e o he hyd ogena ion o enamides 7d and 7e. In a glo ebox, he
app op ia e ole in (0.042 mmol), phosphine-phosphi e ligand (0.46 µmol) and
[Rh(COD)
2
]BF
4
(0.42 µmol) om eshly p epa ed s ock solu ions in CH
2
Cl
2
( o al
olume = 0.5 mL), we e added o a 2 mL glass ial. Vials we e placed in a s eel eac ion
essel model HEL CAT18 ha holds up o eigh een eac ions. The eac o was pu ged
h ee imes wi h H
2
and inally p essu ized o he equi ed p essu e. In he case o
deu e a ion eac ions he eac o was pu ged wi h A , pa ially e acua ed unde acuum
and illed wi h D
2
a 20 a m. A e he desi ed eac ion ime, he eac o was slowly
dep essu ized, solu ions we e e apo a ed and con e sions we e de e mined by
1
H
18
NMR. The esul ing mix u es we e dissol ed in E OAc, and il e ed h ough a sho pad
o silica o emo e ca alys impu i ies. Enan iome ic excess was analyzed by chi al
HPLC, as ollows: N-(7-me hoxy-1,2,3,4- e ahyd onaph halen-2-yl)-ace amide
(8d): HPLC, Daicel Chi alcel OJ-H, n-hexane:i-P OH, 90:10,
1
= 20.6 min,
2
= 32.9
min; N-(8-me hoxy-1,2,3,4- e ahyd onaph halen-2-yl)-ace amide (8e): HPLC,
Daicel Chi alcel OJ-H, n-hexane:i-P OH 90:10,
1
= 12.1 min.,
2
= 13.5 min.
Hyd ogena ion o imine 7 . In a glo ebox, a HEL p essu e eac o (20 mL) was
cha ged wi h imine 7 (0.18 mmol), Ru complex 6b (1.8 µmol),
BuOK (22.0 mg, 0.18
mmol) and isop opanol (2.0 mL). The eac o was pu ged h ee imes wi h H
2
,
p essu ized a 20 a m and hea ed a 60 ºC. A e 24 h, he eac o was slowly
dep essu ized, solu ion was e apo a ed and con e sion was de e mined by
1
H NMR.
The esul ing mix u e was dissol ed in CH
2
Cl
2
, ea ed wi h 2 mL o HCl (2 M) and
s i ed o 20 minu es. Sa u a ed aqueous solu ion o NaHCO
3
(3 mL) was added o he
mix u e, he o ganic laye was sepa a ed and d ied o e magnesium sul a e and
concen a ed. Enan iome ic excesses we e analyzed by chi al HPLC, as ollows: N-
phenyl-1-phenyle hylamine (8 ): Chi alcel OJ-H, hexane-
i
P OH (93:7), low 1.0
mL/min,
1
= 23.0 min (R),
2
= 26.6 min (S);
19
Re e ences
1. Fo e iews in his opic see: a) Leeuwen, P. W. N. M. .; Kame , P. C. J.; Cla e , C.;
Pàmies, O.; Diéguez, M. Chem. Re . 2011, 111, 2077; b) Fe nández-Pé ez, H. C.;
E ayo, P.; Panossian, A.; Vidal-Fe an, A. Chem. Re . 2011, 111, 2119.
2. Sakai, N.; Mano, S.; Nozaki, K.; Takaya, H. J. Am. Chem. Soc. 1993, 115, 7033.
3. Fo applica ions in hyd o o myla ion eac ions, see: a) Nozaki, K.; Sakai, N.; Nanno,
T.; Higashijima, T.; Mano, S.; Ho iuchi, T.; Takaya, H. J. Am. Chem. Soc. 1997, 119,
4413; b) Dee enbe g, S.; Kame , P. C. J.; an Leeuwen, P. W. N. M. O ganome allics
2000, 19, 2065; c) Wa kins, A. L.; Hashiguchi, B. G.; Landis, C. R. O g. Le . 2008, 10,
4553; d) Rubio, M.; Suá ez, A.; Ál a ez, E.; Bianchini, C.; Obe hause , W.; Pe uzzini,
M.; Pizzano, A. O ganome allics 2007, 26, 6428; e) Robe , T.; Abi i, Z.; Wassenaa ,
J.; Sandee, A. J.; Romanski, S.; Neudö l, J. -M.; Schmalz, H.-G.; Reek, J. N. H.
O ganome allics 2010, 29, 478; ) Noonan, G. M.; Fuen es, J. A.; Cobley, C. J.; Cla ke,
M. L. Angew. Chem. In . Ed. 2012, 51, 2477; g) Fe nández-Pé ez, H. C.; Bene -
Buchholz, J.; Vidal-Fe an, A. O g. Le . 2013, 15, 3634.
4. Fo conjuga e addi ions: a) Robe , T.; Velde , J.; Schmalz, H.-G. Angew. Chem. In .
Ed. 2008, 47, 7718; b) Naeemi, Q.; Robe , T.; K anz, D. P.; Velde , J.; Schmalz, H.-G.
Te ahed on: Asymme y 2011, 22, 887; c) Naeemi, Q.; Dinda oğlu, M.; K anz, D. P.;
Velde , J.; Schmalz, H.-G. Eu . J. O g. Chem. 2012, 2012, 1179; d) D usan, M.;
Lölsbe g, W.; Šk o co á, A.; Schmalz, H.-G.; Šebes a, R. Eu . J. O g. Chem. 2012,
2012, 6285; e) Dinda oğlu, M.; Akyol, S.; Şimşi , H.; Neudö l, J.-M.; Bu ke, A.;
Schmalz, H.-G. Te ahed on: Asymme y 2013, 24, 657.
20
5. Hyd obo a ions: Blume, F.; Zemolka, S.; Fey, T.; K anich, R.; Schmalz, H.-G. Ad .
Syn h. Ca al. 2002, 344, 868.
6. Hyd ocyana ions: a) Ho iuchi, T.; Shi akawa, E.; Nozaki, K.; Takaya, H.
Te ahed on: Asymme y 1997, 8, 57; b) Falk, A.; Göde z, A.-L.; Schmalz, H.-G.
Angew. Chem. In . Ed. 2013, 52, 1576.
7. Copolyme iza ion CO/ole ins: a) Nozaki, K.; Sa o, N.; Tonomu a, Y.; Yasu omi, M.;
Takaya, H.; Hiyama, T.; Ma suba a, T.; Koga, N. J. Am. Chem. Soc. 1997, 119, 12779;
b) Fuji a, T.; Nakano, K.; Yamashi a, M.; Nozaki, K. J. Am. Chem. Soc. 2006, 128,
1968.
8. Allyl subs i u ion: a) Dee enbe g, S.; Sch ekke , H. S.; an S ijdonck, G. P. F.;
Kame , P. C. J.; an Leeuwen, P. W. N. M.; F aanje, J.; Goubi z, K. J. O g. Chem.
2000, 65, 4810, b) Pàmies, O.; an S ijdonck, G. P. F.; Diéguez, M.; Dee enbe g, S.;
Ne , G.; Ruiz, A.; Cla e , C.; Kame , P. C. J.; an Leeuwen, P. W. N. M. J. O g. Chem.
2001, 66, 8867; c) Lölsbe g, W.; Ye, S.; Schmalz, H.-G. Ad . Syn h. Ca al. 2010, 352,
2023.
9. Cycloaddi ions: Falk, A.; Fiebig, L.; Neudö l, J.-M.; Adle , A.; Schmalz, H.-G. Ad .
Syn h. Ca al. 2011, 353, 3357.
10. Rh ca alyzed hyd ogena ions: a) Dee enbe g, S.; Pàmies, O.; Diéguez, M.; Cla e ,
C.; Kame , P. C. J.; an Leeuwen, P. W. N. M. J. O g. Chem. 2001, 66, 7626; b)
Pàmies, O.; Diéguez, M.; Ne , G.; Ruiz, A.; Cla e , C. J. O g. Chem. 2001, 66, 8364; c)
Suá ez, A.; Méndez-Rojas, M. A.; Pizzano, A. O ganome allics 2002, 21, 4611; d) Jia,
X.; Li, X.; Lam, W. S.; Kok, S. H. L.; e) Xu, L.; Lu, G.; Yeung, C.-H.; Chan, A. S. C.
Te ahed on: Asymme y 2004, 15, 2273; ) Yan, Y.; Chi, Y.; Zhang, X. Te ahed on:
Asymme y 2004, 15, 2173; g) Rubio, M.; Va gas, S.; Suá ez, A.; Ál a ez, E.; Pizzano,
21
A. Chem. Eu . J. 2007, 13, 1821; h) Fe nández-Pé ez, H.; Donald, S. M. A.; Munslow,
I. J.; Bene -Buchholz, J.; Mase as, F.; Vidal-Fe an, A. Chem. Eu . J. 2010, 16, 6495; i)
Robe , T.; Abi i, Z.; Sandee, A. J.; Schmalz, H.-G.; Reek, J. N. H. Te ahed on:
Asymme y 2010, 21, 2671; j) Fa kas, G.; Balogh, S.; Szöllősy, Á.; Ü ge, L.; Da as, F.;
Bakos, J. Te ahed on: Asymme y 2011, 22, 2104; k) E ayo, P.; Núñez-Rico, J. L.;
Fe nández-Pé ez, H.; Vidal-Fe an, A. Chem. Eu . J. 2011, 17, 13978.
11. Fo examples o hyd ogena ions wi h I ca alys s, see o ins ance: a) Va gas, S.;
Rubio, M.; Sua ez, A.; Pizzano, A. Te ahed on Le . 2005, 46, 2049. b) Núñez-Rico, J.
L.; Fe nández-Pé ez, H.; Bene -Buchholz, J.; Vidal-Fe an, A. O ganome allics 2010,
29, 6627.
12. Fo Ru ca alyzed hyd ogena ions, see: a) Vaque o, M.; Va gas, S.; Suá ez, A.;
Ga cıBa-Ga ido, S. E.; Ál a ez, E.; Mance a, M.; Pizzano, A. O ganome allics 2012, 31,
3551; b) Vaque o, M.; Suá ez, A.; Va gas, S.; Bo a i, G.; Ál a ez, E.; Pizzano, A
Chem. Eu . J. 2012, 18, 15586.
13. a) Chá ez, M. Á.; Va gas, S.; Suá ez, A.; Ál a ez, E.; Pizzano, A. Ad . Syn h.
Ca al. 2011, 353, 2775; b) Núñez-Rico, J. L.; E ayo, P.; Fe nández-Pé ez, H.; Vidal-
Fe an, A. Ad . Syn h. Ca al. 2012, 354, 3025; c) Núñez-Rico, J. L.; Vidal-Fe an, A.
O g. Le . 2013, 15, 2066, d) Kleman, P.; González-Lis e, P. J.; Ga cía-Ga ido, S. E.;
Cadie no, V.; Pizzano, A. Chem. Eu . J. 2013, 19, 16209.
14. a) Va gas, S.; Rubio, M.; Suá ez, A.; del Rio, D.; Al a ez, E.; Pizzano, A.
O ganome allics 2006, 25, 961; b) A ibas, I.; Va gas, S.; Rubio, M.; Suá ez, A.;
Domene, C.; Al a ez, E.; Pizzano, A. O ganome allics 2010, 29, 5791.
15. Fa kas, G.; Balogh, S.; Mada asz, J.; Szollosy, A.; Da as, F.; U ge, L.; Gouygou,
M.; Bakos, J. Dal on T ansac ions 2012, 41, 9493.
22
16. Fo examples o phosphine-phosphi es based on an oxyme hylene b idge, see: a)
A ena, C. G.; D ommi, D.; Fa aone, F. Te ahed on: Asymme y 2000, 11, 4753; b)
A ena, Ca mela G.; Fa aone, F.; G ai , C.; Ti ipicchio, A. Eu . J. Ino g. Chem. 2002,
2002, 711; c) Re . 3 ; d) Re . 3g.
17. Coe, B. J.; Glenw igh , S. J. Coo d. Chem. Re . 2000, 203, 5.
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D. Te ahed on: Asymme y 2004, 15, 2139.
19. The asymme ic hyd ogena ion o β- e alone enamides is a eac ion wi h a high
po en ial due o he pha maceu ical in e es o he esul ing p oduc s. Al hough i has
been a emp ed wi h a wide a ie y o ca alys s, high enan ioselec i i i es ha e only
been achie ed in limi ed cases: a) De ocelle, M.; Mo eux, A.; Agbossou, F.; Do moy,
J.-R. Te ahed on Le . 1999, 40, 4551; b) Renaud, J. L.; Dupau, P.; Hay, A. E.;
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M.; de V ies, J. G.; Reek, J. N. H. Angew. Chem. In . Ed. 2006, 45, 1223; d) Pau igny,
C.; Deboui , C.; Vay on, P.; Ayad, T.; Ra o elomanana-Vidal, V. Te ahed on: Asymm.
2010, 21, 1382; e) Liu, G.; Liu, X.; Cai, Z.; Jiao, G.; Xu, G.; Tang, W. Angew. Chem.
In . Ed. 2013, 52, 4235; ) A ibas, I.; Rubio, M.; Kleman, P.; Pizzano, A. J. O g. Chem.
2013, 78, 3997.
20. Fo o he con ibu ions including examples o he asymme ic hyd ogena ions o β-
e alone enamides, see o ins ance: a) Zhang, Z.; Zhu, G.; Jiang, Q.; Xiao, D.; Zhang,
X. J. O g. Chem. 1999, 64, 1774; b) A goua ch, G.; Samuel, O.; Kagan, H. B. Eu . J.
O g. Chem. 2000, 2885; c) Tang, W.; Chi, Y.; Zhang, X. O g. Le . 2002, 4, 1695; (d)
Hoen, R.; an den Be g, M.; Be nsmann, H.; Minnaa d, A. J.; de V ies, J. G.; Fe inga,
23
B. L. O g. Le . 2004, 6, 1433; e) Be nsmann, H.; an den Be g, M.; Hoen, R.;
Minnaa d, A. J.; Mehle , G.; Ree z, M. T.; De V ies, J. G.; Fe inga, B. L. J. O g. Chem.
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E ayo, P.; Do an, S.; Re és, M.; Ma ín-Gago, P.; G abulosa, A.; Cos an ino, A. R.;
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