1
Highly Enan ioselec i e Imine Hyd ogena ion ca alyzed by Ru henium phosphane-
phosphi e diamine complexes
Mónica Vaque o,[a] And és Suá ez,[a] Se gio Va gas,[a] Gio anni Bo a i,[a] Eleu e io Ál a ez,[a]
An onio Pizzano,*[a]
[a] M. Vaque o, D . A. Suá ez, D . S. Va gas, D . G. Bo a i, D . E. Ál a ez, D . A. 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
A da Amé ico Vespucio 49, Isla de la Ca uja, 41092 Se illa (Spain)
Fax: (+)34-954460565
E-mail: [email p o ec ed]
Dedica ed o P o . José Gimeno on he occasion o his 65 h bi hday
The exceedingly high pe o mance o RuCl2(diphosphane)-(diamine) complexes in he
asymme ic hyd ogena ion o ke ones[1] has ocused a g ea in e es on he eac i i y o Ru(II)
complexes based on phospho us and amino ligands. Thus, a wide di e si y o s uc u ally
ela ed chi al complexes (e. g. RuX2(P-P)(N-N), RuX2(P)2(N-N), RuX2(P-N)2; X = anionic
ligand) has been desc ibed.[2] Mos no ably, hese compounds ha e displayed a ich eac i i y,
p o iding ac i e ca alys s o he hyd ogena ion o di e en ypes o subs a es.[3-5] In addi ion,
applica ions o hese complexes in ca aly ic ans e hyd ogena ion,[6] cycloaddi ion,[7]
conjuga e addi ion,[8] o hyd ocyana ion eac ions,[9] ha e also been epo ed.
Due o he indus ial impo ance o chi al amines, a highly in e es ing applica ion o he
a o emen ioned Ru complexes is he asymme ic ca aly ic hyd ogena ion o imines.[10] As bes
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enan ioselec i i ies o hese subs a es a e no mally achie ed wi h I ca alys s,[11] a gene al
goal in his a ea is he de elopmen o ca alys s based on less cos ly me als.[12] A his ega d,
he g oup o Mo is has epo ed ha se e al Ru hyd ides gi e ac i e ca alys s o imine
hyd ogena ion eac ions, while BINAP complexes wi h DPEN and DACH diamines ga e
mode a e enan ioselec i i ies.[5] Mo eo e , Cobley and cowo ke s, ollowing a sys ema ic
op imiza ion o bo h he diamine and diphosphane ligands, ound a highly enan ioselec i e
ca alys , based on E -DuPHOS and DACH, o he hyd ogena ion o N-(1-
phenyle hylidene)aniline.[13] Ve y ecen ly, Ohkuma e al ha e desc ibed a highly e icien
ca alys based on Xyl-skewphos and DPEN ligands o he hyd ogena ion o a wide ange o
imines.[14]
A ema kable ea u e o RuX2(P-P)(N-N) complexes is he p esence o ou unable
coo dina ing P and N g oups, o e ing a he unlimi ed possibili ies o ca alys op imiza ion.
Among he possible combina ions, pa icula ly appealing o p ac ical easons a e hose based
on only one chi al ligand.[15] Mo eo e , mos o he ca aly ic applica ions desc ibed wi h hese
Ru complexes ha e been pe o med wi h C2-symme ic diphosphane and diamine ligands.
Howe e , he use o unsymme ic biden a e N-N’ ligands (Figu e 1) ha e p oduced ema kable
achie emen s in ke one hyd ogena ion.[16] In con as , he applica ion o phospho us ligands
wi h wo di e en P coo dina ing agmen s (P-P’) is p ac ically unexplo ed, limi ed o he bes
o ou knowledge, o he dias e eoselec i e o ma ion o a highly ac i e ans e hyd ogena ion
ca alys based on a Josiphos diphosphane, epo ed by Ba a a e al.[6c] In his con ibu ion we
deep on he high po en ial o Ru de i a i es based on P-P’ ligands. Thus, a p ac ical highly
enan ioselec i e ca alys o he ca aly ic hyd ogena ion o N-a yl imines, based on an achi al
phosphane-phosphi e and DPEN is desc ibed.
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Figu e 1. Some C1 symme ic N-N’ and P-P’ ligands.
In ecen yea s we ha e s udied he applica ion o a amily o chi al phosphane-
phosphi es (P-OP) in di e se Rh, Ru and I asymme ic ca aly ic hyd ogena ions.[17] The highly
modula s uc u e o hese ligands, he ich ca aly ic eac i i y o RuCl2(diphosphane)(N-N)
complexes and he lack in he li e a u e o phosphane-phosphi e analogues, commi ed us o
in es iga e he p epa a ion o some de i a i es bea ing P-OP ligands. Ini ially, eac ion o
Ru(2-Me-C3H4)2(P-OP)[17 ] wi h wo equi alen s o HCl and one equi alen o (S,S)-DPEN
yielded complexes 1a-1g. Al e na i ely, complexes 2a, 2c and 2d we e p epa ed using (R,R)-
DPEN (Scheme 1a). On he o he hand, ea men o Ru(Cl)2(PPh3)3 wi h one equi alen o
ligand 3, ollowed by a s oichiome ic amoun o DPEN, p o ides an easy access o he desi ed
compounds (Scheme 1b). Depending on he na u e o P-OP and DPEN ligands hese eac ions
p oduced compounds 1 and 2 ei he as a single dias e eome , o as mix u es con aining wo o
h ee isome s, om which he majo one was pu i ied by column ch oma og aphy. In addi ion,
he majo isome can display ei he cis- o ans-dichlo ide coo dina ion depending on he
combina ion o he chela ing ligands (see below).
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Scheme 1. P epa a ion o complexes 1 and 2.
We ha e nex sc eened he pe o mance o complexes 1 and 2 in he enan ioselec i e
hyd ogena ion o N-(1-phenyle hylidene)aniline 4a (Scheme 2, Table 1). As a i s app oach,
simila eac ion condi ions o hose epo ed by Cobley we e used (i. e. S/C = 100, iP OH as
sol en , 20 ba H2, [4a]/[K BuO] = 1, 60 ºC).[13] Unde hese condi ions compounds 1a and 1b
ga e mode a e con e sions, while he diphenyl ca alys p o ided a signi ican ly be e
enan ioselec i i y (en ies 1, 2, Table 1). Mo eo e , p eca alys s wi h a smalle phosphi e
agmen 1c (en y 3) and an e hane backbone 1d (en y 4) we e also examined. None o hem
inc eased he enan ioselec i i y p o ided by 1a, al hough he e hane b idged ca alys , p obably
due o a mo e lexible backbone, p oduced a highe con e sion. To examine ma ching e ec s
be ween diamine and P-OP ligands dias e eome ic complex 2a was also es ed. This compound
p oduced a simila con e sion and a highe enan ioselec i i y (90 % ee, en y 8) han 1a. These
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esul s indica e ha he chi al induc ion is e y p edominan ly caused by he diamine ligand and
ha he s e eogenic axis o he phosphi e has a seconda y ole. Following his easoning we
nex examined complex 1e bea ing a con o ma ionally lexible phosphi e agmen . We we e
pleased o obse e ha his compound p oduced he same enan ioselec i i y han 2a (90 % ee,
en y 5) bu wi h be e con e sion. In e es ingly, hese esul s indica e ha an impo an
a iable is phosphi e lexibili y, which enables a highe ca alys eac i i y, while he use o a
mo e igid phosphi e agmen wi h a s e eogenic axis e a ds he eac ion and does no imp o e
enan ioselec i i y. In addi ion, hese esul s enable a u he op imiza ion o he ca alys using
o he achi al P-OP ligands di e ing on he phosphane g oup. Then, complexes 1 and 1g
bea ing p- olyl and xylyl phosphane subs i uen s we e examined. While he la e p oduced
mode a e le els o con e sion and enan ioselec i i y (en y 7), ca alys p ecu so 1 p o ided a
highe enan ioselec i i y han 1a, wi h an impo an imp o emen on con e sion (en y 6).
Scheme 2. Ca aly ic Hyd ogena ion o N-a yl imines.

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Table 1. Hyd ogena ion o 4a wi h complexes 1, 2[a]
En y
P-OP
N-N
Con [%]
Ee [%]
Con ig
1
3a
(S,S)-DPEN
39
80
R
2
3b
47
32
R
3
3c
55
58
R
4
3d
72
73
R
5
3e
67
90
R
6
3
97
93
R
7
3g
78
72
R
8
3a
(R,R)-DPEN
39
90
S
9
3c
24
12
S
10
3d
70
54
S
[a] Reac ions we e ca ied ou a 60 ºC using 0.1 M solu ions o subs a e and K BuO
as base (B), S/C/B = 100/1/100, eac ion ime 72 h. Con e sion was de e mined by
1H NMR and enan iome ic excess by Chi al HPLC. Con igu a ion was de e mined by
compa ison o sign o op ical o a ion wi h li e a u e da a (see suppo ing
in o ma ion).
Mos ema kably, p eca alys 1 showed a high eac i i y in oluene, enough o comple e
eac ions unde e y mild condi ions a lowe ca alys and base loadings ( oom empe a u e, 4
ba H2, S/C/B = 500/1/10). Unde hese condi ions a 93 % ee in he hyd ogena ion o 4a was
eached (en y 1, Table 2). These esul s p omp ed us o in es iga e he scope o he p esen
ca aly ic sys em. We we e pleased o obse e ha di e se N-a yl imines 4 we e hyd ogena ed
wi h high le els o con e sion and enan ioselec i i ies unde hese eac ion condi ions (Scheme
2). In gene al, N-phenyl imines ga e somewha lowe enan ioselec i i ies (91-93 % ee, en ies
1-4), han N-(p-anisyl) imines, which p o ided alues om 93 o 96 % ee (en ies 5, 6, 8, 10-
12), in good acco d wi h p e ious obse a ions.[11g, 14] Du ing his sc eening we ha e obse ed
ha subs a es 4g and 4h ga e uncomple ed eac ions unde he la e eac ion condi ions. An
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inc ease in he p essu e o 10 ba o hyd ogen p oduced amine 5g wi h ull con e sion and a 95
% ee (en y 8). In he case o he i luo ome hyl subs i u ed imine 4h, eac ion in iP OH unde
20 ba showed ull con e sion wi h a 93 % ee (en y 10). Finally, N-(p-me hoxyphenyl)-1-
phenylp opylamine 5j was ob ained wi h a 95 % ee and comple e con e sion by hyd ogena ion
o he co esponding imine 4j (en y 12).
Table 2. Hyd ogena ion o imines 4 wi h complex 1 [a]
En y
Subs a e
H2 [ba ]
Con [%]
Ee [%]
Con ig[b]
1
4a
4
> 99
93
R
2
4b
4
> 99
93
-
3
4c
4
> 99
91
R
4
4d
4
> 99
92
-
5
4e
4
> 99
95
R
6
4
4
> 99
96
R
7
4g
4
73
89
R
8
4g
10
> 99
95
R
9
4h
4
26
81
R
10[c]
4h
20
> 99
93
R
11
4i
4
> 99
96
-
12
4j
4
> 99
95
R
[a] Reac ions we e ca ied ou a oom empe a u e in oluene wi h K BuO as base
(B), S/C/B = 500/1/10, eac ion ime 24 h and [S] = 1.0 M, unless o he wise
speci ied. Con e sion was de e mined by 1H NMR and enan iome ic excess by Chi al
HPLC. [b] Con igu a ion was de e mined by compa ison o sign o op ical o a ion
wi h li e a u e da a when a ailable (see suppo ing in o ma ion), o he wise he op ical
o a ion sign is p o ided. [c] Reac ion pe o med a 60 ºC in iP OH.
Wi h he in en ion o gain addi ional in o ma ion abou he s e eochemis y o Ru
complexes, ep esen a i e examples 2d and 1e we e s uc u ally cha ac e ized by X- ay
c ys allog aphy.[18] Bo h compounds show a dis o ed oc ahed al s uc u e and no ewo hy
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di e in he coo dina ion posi ions o chlo ide ligands. Complex 2d shows a cis a angemen
wi h one o he chlo ides ans o he phosphi e g oup (Figu e 2). In addi ion, his s uc u e
displays a signi ican ans in luence o he phosphi e g oup as he Ru-Cl(2) dis ance is
app eciable longe han ha Ru-Cl(1) (2.475 and 2.409 Å, espec i ely). In con as , s uc u e
o compound 1e shows wo chlo ides in wo mu ually ans posi ions (Figu e 3). A ema kable
ea u e o his compound is he exis ence in he c ys al o wo dias e eome ic molecules
di e ing in he con o ma ion o he biphenyl agmen . The dissimila i y be ween he wo
s uc u es is no es ic ed o he phosphi e agmen , as he change in bia yl con o ma ion is
coupled wi h opposed con o ma ions o he benzene backbone and he phosphane g oup. Thus,
i he diamine backbone is igno ed bo h s uc u es a e nea ly enan iome ic each o he . In
solu ion, howe e , only one se o signals composed by wo double s cen e ed a 146.1 and 38.7
ppm [J(P,P) = 73 Hz], was obse ed by 31P{1H} NMR a oom empe a u e. Upon cooling,
signals b oadened and a -90 ºC wo species in a 2:1 a io we e obse ed. The majo species
appea ed as wo double s cen e ed a 149.5 and 37.3 ppm [J(P,P) = 71 Hz], while he mino one
is cha ac e ized by wo double s a 148.8 and 36.9 ppm [J(P,P) = 73 Hz]. These obse a ions
a e in acco d wi h a as exchange be ween he wo dias e eome s upon a opisome iza ion o
he phosphi e g oup a oom empe a u e, as obse ed in hodium de i a i es bea ing his
phosphi e agmen .[19] The e o e, he chi al diamine does no e icien ly a ou a phosphi e
bia yl con o ma ion, as obse ed be o e in he case o complexes based on con o ma ionally
lexible diphosphanes.[20]
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Figu e 2. ORTEP iew o complex 2d.
The high enan ioselec i i y p o ided by 1e, along wi h he lack o chi al con ol o he
diamine in phosphi e con o ma ion cons i u e a ema kable aspec which dese es u he
commen . Assuming ha he hyd ogena ion o N-a yl imines p oceeds in an analogous manne
o ke one hyd ogena ion,[21] se e al s uc u es o he key dihyd ide wi h cis hyd ide and amino
ligands a e possible.[22] Namely, a ans dihyd ide A (Figu e 4) and dias e eome ic cis
s uc u es B and C di e ing in he ela i e posi ions o he P unc ionali ies (only dias e eome s
co esponding o  Ru con igu a ion a e shown). Among hese s uc u es, dihyd ide B, which is
s uc u ally simila o 2d, places he mo e eac i e hyd ide (acco ding o he highe phosphi e
ans in luence o e ha o he amino ligand) in a ans posi ion o he phosphi e g oup. This
a angemen would minimize he in luence o phosphi e con o ma ion on asymme ic
induc ion, in good acco d wi h expe imen al esul s. This p oposal inds u he suppo on he
s e eochemical model p oposed by Ohkuma, based on a cis dihyd ide in which he apical
hyd ide, ans o a phosphane ligand, is ans e ed o he N-a yl imine.[14] Mo eo e , he
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M. Vaque o, S. Va gas, A. Suá ez, S. E. Ga cıa-Ga ido, E. Ál a ez, M. Mance a, A.
Pizzano, O ganome allics 2012, 31, 3551-3564.
[18] CCDC 894893 (1e) and CCDC-894894 (2d) con ain he supplemen a y c ys allog aphic
da a o his pape . These da a can be ob ained ee o cha ge om The Camb idge
C ys allog aphic Da a Cen e ia www.ccdc.cam.ac.uk/da a_ eques /ci .
[19] a) G. J. H. Buisman, M. E. Ma in, E. J. Vos, A. Kloo wijk, P. C. J. Kame , P. W. N. M.
an Leeuwen, Te ahed on: Asymme y 1995, 6, 719-738; b) M. Rubio, A. Suá ez, D. del
Rio, A. Galindo, E. Ál a ez, A. Pizzano, O ganome allics 2009, 28, 547-560.
[20] a) K. Mikami, T. Ko enaga, M. Te ada, T. Ohkuma, T. Pham, R. Noyo i, Angew. Chem.
In . Ed. 1999, 38, 495-497; b) T. Ko enaga, K. Aikawa, M. Te ada, S. Kawauchi, K.
Mikami, Ad . Syn h. Ca al. 2001, 343, 284-288.
[21] a) K. Abdu -Rashid, S. E. Clapham, A. Hadzo ic, J. N. Ha ey, A. J. Lough, R. H.
Mo is, J. Am. Chem. Soc. 2002, 124, 15104-15118; b) C. A. Sando al, T. Ohkuma, K.
Muñiz, R. Noyo i, J. Am. Chem. Soc. 2003, 125, 13490-13503.
[22] a) R. Abbel, K. Abdu -Rashid, M. Faa z, A. Hadzo ic, A. J. Lough, R. H. Mo is, J. Am.
Chem. Soc. 2005, 127, 1870-1882; b) K. Abdu -Rashid, R. Abbel, A. Hadzo ic, A. J.
Lough, R. H. Mo is, Ino g. Chem. 2005, 44, 2483-2492.