Efficient and selective hydrogenation of amides to alcohols and amines using a well-defined manganese–PNN pincer complex
Abstract
Peer reviewed
Full text
Efficien and selec i e hyd ogena ion o amides o
alcohols and amines using a well-defined
manganese–PNN pince complex†
Ve onica Papa,‡
a
Jose R. Cab e o-An onino,‡
a
Elisabe a Albe ico,
ab
Anke Spannebe g,
a
Ka h in Junge,
a
Hen ik Junge
a
and Ma hias Belle *
a
No el well-defined NNP and PNP manganese pince complexes ha e been syn he ized and ully
cha ac e ized. The ca alys Mn-2 con aining an imidazolyaminolphosphino ligand shows high ac i i y and
selec i i y in he hyd ogena ion o a wide ange o seconda y and e ia y amides o he co esponding
alcohols and amines, unde ela i ely mild condi ions. Fo he fi s ime, mo e challenging subs a es like
p ima y a oma ic amides including an ac ual he bicide can also be hyd ogena ed using his ea h-
abundan me al-based pince ca alys .
In oduc ion
Reduc ion o ca boxylic acid de i a i es ep esen s an impo -
an p ocess in o ganic syn hesis wi h po en ial applica ion in
bo h indus ial and academic se ings.
1,2
T adi ionally, his eac ion is pe o med using an excess o
educing agen s
3
p oducing s oichiome ic amoun s o was e-
p oduc s.
4
In con as , ca aly ic hyd ogena ion using molecula
hyd ogen is a much mo e a om-economical and was e- ee
app oach.
4c,5
Un o una ely, amides cons i u e one o he leas
eac i e de i a i es among all classes o ca bonyl compounds
because o he low elec ophilici y o he ca bonyl g oup. Thus,
hei educ ion equi es ha sh condi ions (high p essu es and
empe a u es) and con inues o be a challenging goal.
6
In
gene al, he hyd ogena ion o amides p oceeds h ough
hemiaminal o ela ed in e media es.
5a,7
He e, wo diffe en
pa hways (C–Oo C–N bond b eaking, hyd ogena ion and
hyd ogenolysis, espec i ely) can occu (Scheme 1).
5c
The C–O
clea age pa hway o ms he highe amine as he p oduc wi h
Scheme 1 Possible eac ion pa hways o he hyd ogena ion o
amides.
Scheme 2 Hyd ogena ion o amides o alcohols and amines ca alyzed
by: (a) u henium (p e ious wo k), (b) i on (p e ious wo k) and (c)
manganese ( his wo k).
a
See ESI o o he examples o Ru–pince
ca alys s epo ed o his eac ion (Scheme S1†).
a
Leibniz-Ins i u ¨
u Ka alyse, e.V. Albe -Eins ein S . 29a, 18059 Ros ock, Ge many.
E-mail: ma hias.belle[email p o ec ed]
b
Ins i u o di Chimica Biomolecola e, Consiglio Nazionale delle Rice che, T . La C ucca
3, 07100 Sassa i, I aly
†Elec onic supplemen a y in o ma ion (ESI) a ailable: Gene al expe imen al
p ocedu es, addi ional schemes and gu es, cha ac e iza ion da a and NMR
spec a a e a ailable. See DOI: 10.1039/c7sc00138j
‡V. P. and J. R. C.-A. con ibu ed equally o his wo k.
Ci e his: Chem. Sci.,2017,8,3576
Recei ed 11 h Janua y 2017
Accep ed 24 h Feb ua y 2017
DOI: 10.1039/c7sc00138j
sc.li/chemical-science
3576 |Chem. Sci.,2017,8, 3576–3585 This jou nal is © The Royal Socie y o Chemis y 2017
Chemical
Science
EDGE ARTICLE
Open Access A icle. Published on 08 Ma ch 2017. Downloaded on 1/7/2025 4:27:29 PM.
This a icle is licensed unde a
C ea i e Commons A ibu ion 3.0 Unpo ed Licence.
View A icle Online
View Jou nal
| View Issue
emo al o H
2
O (Scheme 1, pa h A), while he C–N clea age
p oduces he dep o ec ed amine and he co esponding alcohol
by collapse o he in e media e hemiaminal (Scheme 1, pa h B).
In he pas decade, signican imp o emen s in amide
hyd ogena ion using bo h he e ogeneous and homogeneous
ca alys sha ebeenachie ed.Whilesomeo hehe e ogeneous
ca alys s, e.g. Re–Pd/C, wo k unde compa ably mild condi ions,
hey p oceed ia pa h A (Scheme 1). No ably, hese p ecious me al
sys ems a e incompa ible wi h a oma ic and some o he sensi i e
unc ional g oups which can be easily educed.
8
No hyd ogena-
ion o a oma ic ings has been obse ed using homogeneous
u henium/1,1,1- is(diphenylphosphino-me hyl)e hane ( iphos)-
based sys ems in combina ion wi h specic acidic addi i es, as
epo ed by Cole-Hamil on's, Lei ne and Klanke maye 's, Qi-Lin
Zhou's g oups.
2b,9
Recen ly, we ha e demons a ed ha such
ca alys s also educe he amide ca bonyl g oup o he hemi-
aminal, which collapses o gi e he alcohol and he non-alkyla ed
amine (pa hway B). In e es ingly, hese compounds hen p oduce
he alkyla ed amine ia a hyd ogen bo owing mechanism.
9d
In
addi ion, an elegan deoxygena i e hyd ogena ion o amides
using a well-dened i idium pince complex in he p esence o
a s oichiome ic amoun o bo on Lewis acid was also epo ed.
10
On he o he hand, homogeneous pince ca alys s making
use o me al–ligand coope a ion,
11
ha e shown no able ac i i y
o he hyd ogena ion o he amide by C–N bond clea age
(Scheme 1, pa h B). This ans o ma ion allows o ob ain alco-
hols and amines om amides and is o in e es as selec i e
dep o ec ion me hodology in o ganic syn hesis.
The s example o his hyd ogenolysis o amides o alco-
hols and amines was epo ed by Mils ein using a well-dened
u henium pince complex.
12
Subsequen ly, o he examples,
mainly based in u henium, we e published by Ika iya, Sai o,
Be gens, Mashima, Zhang and ou g oup (Scheme 2(a)).
13
In gene al, he eplacemen o noble me als wi h inexpensi e
and abundan s ow me als is an ac ual goal o ca alysis as well
as o ganome allic chemis y and a ac i e in e ms o
Scheme 3 Syn hesis o pince ligand (1) and manganese complexes (Mn-1,Mn-2 and Mn-3).
This jou nal is © The Royal Socie y o Chemis y 2017 Chem. Sci.,2017,8, 3576–3585 | 3577
Edge A icle Chemical Science
Open Access A icle. Published on 08 Ma ch 2017. Downloaded on 1/7/2025 4:27:29 PM.
This a icle is licensed unde a
C ea i e Commons A ibu ion 3.0 Unpo ed Licence.
View A icle Online
sus ainabili y.
14
Recen effo s by Mils ein's, San o d's and Lang-
e 's g oups in his di ec ion ha e led o he de elopmen o h ee
homogeneous i on based ca alys s o his impo an ans-
o ma ion (Scheme 2(b)).
15
Howe e , ca alys s Fe-1o Fe-2(a,b)
15
affo ded modes con e sions and yields, and/o equi ed o cing
condi ions, o ha e a na ow scope which is limi ed o ac i a ed
subs a es like uo ine-con aining amides o o mamides.
In addi ion o i on, manganese is one o he mos abundan
me als in he ea h c us and plays an impo an ole in human
biochemis y. In gene al, Mn-based complexes we e employed in
ca aly ic oxida ion eac ions. Mo eo e , special hyd osilyla ion
and elec oca aly ic eac ions we e epo ed.
16
Ve y ecen ly, he
design and de elopmen o new Mn-based complex ca alys s o
o he applica ions, e.g. educ ion eac ions, became e y appea-
ling.
16b,17,18
In his con ex , he e we desc ibe he syn hesis o h ee
no el well-dened Mn–pince complexes and hei ca aly ic
applica ionin heefficien and selec i e hyd ogena ion o
seconda y and e ia y amides o he co esponding alcohols and
amines unde ela i ely mild condi ions. In addi ion, mo e
challenging subs a es like p ima y benzamides could be hyd o-
gena ed in mode a e yields. To he bes o ou knowledge, wi h
he excep ion o he p e iously epo ed i on-based sys ems, he e
is no ano he example o his ans o ma ion ca alyzed by non-
noble me al-based ca aly ic sys em.
Resul s and discussion
Ligand and me al complex syn hesis
In p e ious s udies, he impo an ole o pince ligands o
bi unc ional hyd ogena ions was cla ied.
19
While mos ca a-
lys s a e based on PNP ligands, o he complexes which combine
soand ha d dono s and/o hemilabile g oups ha e been
shown o be benecial in es e
2a,20
and amide educ ion.
12b
Following ou p e ious wo k conce ning he syn hesis o he
NNP- ype imidazolylphosphine pince ligand amily and he
co esponding u henium complexes,
21
ha we e success ully
applied in amide hyd ogena ion,
13g
we en isaged he possibili y
o p epa e he s Mn–NNP imidazolylphosphine pince
complexes and o es hei po en ial as educ ion ca alys s. Fo
his pu pose, ini ially he NNP pince ligand 2-(diisop opyl-
phosphanyl)-N-[(1-me hyl-1H-imidazol-2-yl)me hyl]e han-1-
amine 1(Scheme 3), was p epa ed in a one-po wo-s ep syn-
hesis.
13g,21
When ligand 1was eac ed wi h comme cially
a ailable Mn(CO)
5
B in oluene upon i adia ion wi h UV ligh
o 3 hou s, Mn-1 was ob ained in 60% yield (Scheme 3).
22
To
ou deligh he complex was c ys allized by apou diffusion o
n-hep ane in o a concen a ed DCM solu ion o he compound
and he molecula s uc u e was de e mined by X- ay diff ac ion
(Fig. S1,†ESI). The molecula s uc u e shows a dis o ed
igonal bipy amidal geome y in which he ligand is coo di-
na ed o he manganese in a ipodal ashion.
Fig. 1 Molecula s uc u e o manganese complex Mn-2 wi h he mal
ellipsoids d awn a he 30% p obabili y le el. Hyd ogen a oms o he
han H3 ha e been omi ed o he sake o cla i y.
Table 1 Hyd ogena ion o benzanilide 2 o aniline 3and benzyl alcohol 4wi h manganese complexes Mn-1–3
En y
a
H
2
(ba ) T(C) Mn-ca . (mol%) KO
Bu (mol%) Con .
b
(%) 3
b
(%) 4
b
(%)
1 50 130 —15 ———
2 50 130 Mn-1 (4) 15 ———
3 50 130 Mn-2 (4) 15 >99 >99 98
4 50 130 Mn-3 (4) 15 ———
5 50 130 Mn-2 (4) ————
6 50 130 Mn-2 (4) 10 >99 97 91
7 30 130 Mn-2 (4) 10 >99 96 93
8 30 120 Mn-2 (4) 10 >99 >99 90
9 30 120 Mn-2 (2.5) 10 98 90 89
10 30 120 Mn-2 (2.5) 8 95 89 82
11 30 120 Mn-2 (2.5) 6 72 65 62
12 30 120 Mn-2 (2.5) 4 51 45 40
13 30 120 Mn-2 (1.5) 8 47 32 29
a
S anda d eac ion condi ions: benzanilide 2(49.30 mg, 0.25 mmol), Mn-ca . (2.5–4 mol%), KO
Bu (4–15 mol%), -amylOH (2 mL), 30–50 ba o H
2
,
120 C o e 16 h.
b
Con e sion o 2and yields o 3and 4we e calcula ed by GC using hexadecane as ex e nal s anda d.
3578 |Chem. Sci.,2017,8,3576–3585 This jou nal is © The Royal Socie y o Chemis y 2017
Chemical Science Edge A icle
Open Access A icle. Published on 08 Ma ch 2017. Downloaded on 1/7/2025 4:27:29 PM.
This a icle is licensed unde a
C ea i e Commons A ibu ion 3.0 Unpo ed Licence.
View A icle Online
In addi ion, a Mn(I) complex was p epa ed by addi ion o he
manganese p ecu so o ligand 1in e hanol a 90 C in he
absence o ligh . In his way he is-ca bonyl ionic NNP Mn(I)
complex Mn-2 is o med in 95% yield (Scheme 3). C ys als
sui able o X- ay diff ac ion analysis we e ob ained by slow
e apo a ion o an e hanolic solu ion unde a gen le ow o
a gon. Compa ed o complex Mn-1 he molecula s uc u e
shown in Fig. 1
23
exhibi s a dis o ed oc ahed al geome y in
which he PNN ligand adop s a acial coo dina ion, one CO
ligand is ans o he cen al alipha ic ni ogen, hus ac ing as
a ipodal ligand a he han pince , simila o he p e iously
epo ed PNP–Mn complex.
18h
The s uc u e o Mn-2 was u he
p o en by NMR and IR spec oscopy, high esolu ion mass
spec oscopy and elemen al analysis (Fig. S9, see ESI†).
In gene al, he complex has a low molecula symme y (C
1
is
he symme y poin g oup) and i s IR spec um shows h ee
bands in he ca bonyl egion a 2027, 1943 and 1916 (pa ly
o e lapping) cm
1
which demons a es he p esence o h ee
CO molecules coo dina ed o he me al cen e .
Fo compa a i e ca aly ic s udies, in addi ion o he wo well-
dened Mn-1 and Mn-2 NNP pince complexes, he syn hesis o
an ionic PNP Mn(I) complex Mn-3 was also pe o med ( he
molecula s uc u e o his complex is shown in Fig. S10, see
ESI†). All he complexes syn hesized a e s able and do no
decompose easily in he p esence o ai , he ca aly ic p ope ies
esul unal e ed ae one mon h.
Ca aly ic hyd ogena ion o amides using Mn–pince
complexes
To es he po en ial o he new complexes as ca alys s, he
hyd ogena ion o benzanilide 2 o affo d aniline 3and benzyl
alcohol 4was chosen as benchma k eac ion.
Ini ially he h ee complexes we e es ed using 4 mol% o Mn
ca alys s unde 50 ba o H
2
and 130 Cin hep esenceo asligh
excess o base
24
and -amyl alcohol as sol en . Unde hese
condi ions only complex Mn-2 showed ac i i y affo ding p oduc s
3and 4in quan i a i e yields (Table 1, en y 2–4). Nex , a ia ions
Fig. 2 S udy o he sol en effec in he hyd ogena ion o benzanilide 2 o aniline 3and benzyl alcohol 4ca alyzed by Mn-2 complex. S anda d
eac ion condi ions: benzanilide 2(49.30 mg, 0.25 mmol), Mn-2 (1.78 mg, 0.00375 mmol, 1.5 mol%), KO
Bu (2.13 mg, 0.019 mmol, 8 mol%),
sol en (2 mL), 30 ba o H
2
, 120 C o e 16 h. Con e sion o 2and yields o 3and 4we e calcula ed by GC using hexadecane as ex e nal s anda d.
Table 2 Hyd ogena ion o benzanilide 2 o aniline 3and benzyl
alcohol 4wi h manganese complex Mn-2:fine uning o eac ion
condi ions
En y
a
T
(C)
Mn-2
(mol%)
KO
Bu
(mol%)
Con .
b
(%)
3
b
(%)
4
b
(%)
1 120 1.5 8 >99 96 90
2 100 2 10 >99 96 90
3 100 2 8 95 88 80
4 100 2 5 29 24 24
5
c
100 2 10 58 57 44
6 100 1.5 10 79 67 60
7 80 2 10 18 8 —
8
d
100 2 10 ———
9
e
100 2 10 ———
10
100 2 10 63 53 50
a
S anda d eac ion condi ions: benzanilide 2(49.30 mg, 0.25 mmol),
Mn-2 (1.5–2 mol%), KO
Bu (5–10 mol%), cyclohexane (2 mL), 15–30
ba o H
2
, 100–120 C o e 16 h.
b
Con e sion o 2and yields o 3and
4we e calcula ed by GC using hexadecane as ex e nal s anda d.
c
Run
a 15 ba o H
2
.
d
Run wi h 2 mol% o ligand 1in he absence o Mn-2
complex.
e
Run wi h 2 mol% o Mn(CO)
5
B in he absence o Mn-2
complex.
Run wi h 2 mol% o ligand 1and 2 mol% o Mn(CO)
5
B .
This jou nal is © The Royal Socie y o Chemis y 2017 Chem. Sci.,2017,8,3576–3585 | 3579
Edge A icle Chemical Science
Open Access A icle. Published on 08 Ma ch 2017. Downloaded on 1/7/2025 4:27:29 PM.
This a icle is licensed unde a
C ea i e Commons A ibu ion 3.0 Unpo ed Licence.
View A icle Online
Table 3 Subs a e scope in he hyd ogena ion o amides o alcohols and amines ca alyzed by Mn-2 complex
En y
a
Amide Mn-2 (mol%) Con .
b
(%) Yield o amine
b
(%) Yield o alcohol
b
(%)
12 >99 96 90
229488 85
32 >99 90 n.d.
429084 80
548581 75
64 >99 >99 >99
739485 80
8
c
3 >99 >99 90
949594 90
10 48582 80
11 4 >99 98 94
12 49592 90
13
c
4 >99 >99 >99
14
d
29590 85
15
c,d
28281 78
3580 |Chem. Sci.,2017,8, 3576–3585 This jou nal is © The Royal Socie y o Chemis y 2017
Chemical Science Edge A icle
Open Access A icle. Published on 08 Ma ch 2017. Downloaded on 1/7/2025 4:27:29 PM.
This a icle is licensed unde a
C ea i e Commons A ibu ion 3.0 Unpo ed Licence.
View A icle Online
o p essu e, empe a u e, ca alys loading and base concen a ion
we e pe o med (Table 1, en y 6–13). I was ound ha Mn-2 was
efficien also unde milde condi ions (30 ba o H
2
, 120 C, 10
mol% KO
Bu), e en i he ca alys loading was educed o 2.5 mol%
(Table 1, en y 9) and he p oduc s 3and 4we e ob ained in 90%
and 89% yields, espec i ely. Howe e a u he educ ion o he
amoun o ca alys o base was de imen al (Table 1, en ies 10–13).
No ably, no eac ion ook place in he absence o base as p edic -
able in a sys em wi h non-innocen pince ligand (Table 1, en y 5).
This effec o he base sugges s ha he ac i e ca aly ic species is
he amido complex, ob ained by dep o ona ion o N–Hand
esul ing in he elease o one CO molecule. Then he p oposed
mechanism migh s be he ou e sphe e ca aly ic cycle al eady
in es iga e in p e ious wo k ega ding hyd ogena ion o ca boxylic
de i a i es ca alyzed by hese ype o pince complexes.
2a,13g,18g,h
Nex , we explo ed he sol en effec on he ca aly ic ac i i y o
Mn-2 (Fig. 2).
In o de o obse e posi i e o nega i e effec s o he diffe en
sol en s, he sc eening was ca ied ou a 30 ba o H
2
and
120 C using 1.5 mol% Mn-2 and 8 mol% o base. Su p isingly,
among all he sol en s es ed (mo e han 13), cyclohexane was
ound o gi e he bes esul s o his sys em (Fig. 2). This is
a a he unexpec ed effec o his ype o eac ions and e he -,
alcohol-, a ene-, and uo ina ed-sol en s as well as o he
alkanes p o ided signican ly lowe ac i i ies. In his con ex , i
is in e es ing o no e ha cyclohexane allowed o efficien
ans e hyd ogena ion o ni iles ca alyzed by a well-dened
NNP Co imidazolylphosphine pince complex.
25
Ha ing iden ied cyclohexane as he bes sol en o ou
eac ion, a ne uning o he ini ially selec ed op imized
condi ions was ca ied ou . Ca aly ic ac i i y did no dec ease
when he empe a u e was educed om 120 C o 100 C and
he ca alys loadings om 2.5 o 2 mol% (Table 2, en y 2).
In con as , a subs an ial dec ease o base loadings had
a signican impac (Table 2, en ies 3 and 4). Addi ional
mi iga ion o he eac ion empe a u e, hyd ogen p essu e and
ca alys loading had nega i e effec s on he ac i i y (Table 2,
en ies 5–7). Finally, when he eac ion was conduc ed in he
p esence o ei he ligand 1o me al p ecu so no con e sion
was obse ed (Table 2, en ies 8 and 9). No iceable, in si u
combina ion o Mn(CO)
5
B and ligand 1also affo ded mode -
a ed ac i i y in he eac ion (Table 2, en y 10).
A his s age we decided o s udy he gene al applicabili y o
he no el Mn-2 complex in he hyd ogena ion o a wide ange o
diffe en seconda y and e ia y amides o he co esponding
alcohols and amines (Table 3). Mos subs a es we e hyd oge-
na ed in good o excellen yields unde he p e iously selec ed
op imized condi ions a 100 C, 30 ba o hyd ogen o e 16 h
using cyclohexane as sol en .
Table 3 (Con d.)
En y
a
Amide Mn-2 (mol%) Con .
b
(%) Yield o amine
b
(%) Yield o alcohol
b
(%)
16
d
3 >99 >99 >99
17
c,d
4 >99 >99 90
18
c,d
59897 96
a
S anda d eac ion condi ions: amide (0.25 mmol), Mn-2 ca . (2–5 mol%), KO
Bu (2.8 mg, 0.025 mmol, 10 mol%), cyclohexane (2 mL), 30 ba o H
2
,
100 C o e 16 h.
b
Con e sion o he amide and yield o he alcohol and amine we e calcula ed by GC using hexadecane as ex e nal s anda d.
c
The
eac ion was ca ied ou using cyclohexane/ -amylOH (1.5/0.5) mix u e as sol en (2 mL).
d
Run a 120 C.
Scheme 4 Hyd ogena ion o p ima y amides o co esponding alco-
hols ca alyzed by Mn-2 complex. S anda d eac ion condi ions: amide
(0.25 mmol), KO
Bu (3 eq. o Mn), cyclohexane/ -amylOH (1.5/0.5)
mix u e (2 mL), 50 ba o H
2
and 140 C. Specific eac ion condi ions
o benzamide: Mn-2 (5 mol%) o e 48 h, o nico inamide: Mn-2 (7
mol%) o e 24 h, o p-( ifluo ome hyl)benzamide and 4-me hox-
ybenzamide: Mn-2 (5 mol%), o e 24 h. Con e sion o he amide and
yields o he co esponding benzyl alcohols we e calcula ed by GC
using hexadecane as ex e nal s anda d.
This jou nal is © The Royal Socie y o Chemis y 2017 Chem. Sci.,2017,8, 3576–3585 | 3581
Edge A icle Chemical Science
Open Access A icle. Published on 08 Ma ch 2017. Downloaded on 1/7/2025 4:27:29 PM.
This a icle is licensed unde a
C ea i e Commons A ibu ion 3.0 Unpo ed Licence.
View A icle Online
E en less eac i e elec ophilic amides we e con e ed in e y
good yields using up o 5 mol% ca alys loading a 100–120 C. Fo
ins ance, educ ion o diffe en uo o- and chlo o-subs i u ed
amides p oceeded smoo hly and no dehalogena ion p oduc s
we e de ec ed. No ably, also highly sensi i e iodide was ully
ole a ed (Table 3, en ies 4–8 and 13). G a i yingly, benzyl-
subs i u ed amides (Table 3, en y 11) and amides con aining
elec on-dona ing g oups such as me hoxy affo ded e y high
con e sions (Table 3, en ies 12 and 15). No iceably, Mn-2 allowed
he hyd ogena ion o N-ace yl-1,2,3,4- e ahyd oquinoline (Table
3, en y 2), as well as N-(naph halen-1-yl)ace amide (Table 3, en y
14) and impo an bioac i e py idine-con aining amides (Table 3,
en ies 17 and 18).
Te ia y amides including s e ically hinde ed subs a es
we e also success ully hyd ogena ed in he p esence o his
manganese complex. Thus, N,N-diphenylace amide (Table 3,
en y 10) and iuo ome hyl-ac i a ed amides (Table 3, en ies
3 and 16) affo ded excellen con e sion and yields.
Un o una ely he educ ion o alipha ic N-alkyl amide as
N,N-dime hyloc anamide o non ac i a ed N-alkyl subs i u ed
benzamides, ailed wi h his ca aly ic sys em.
So a , hyd ogena ion o p ima y amides –mo e challenging
subs a es – o he co esponding alcohols and ammonia has
been sca cely in es iga ed.
12b
Few examples o educ ion
sys ems a e known o be ac i e o his ype o subs a es such as
SmI
2
-based sys em
12c
and he well-dened NNP u henium
imidazolylphosphine pince complex p e iously epo ed by
us.
13g
The e o e, a his s age we explo ed he hyd ogena ion o
diffe en benzamides in he p esence o Mn-2 (Scheme 4). To
ou deligh , benzamide and p-me hoxybenzamide bu also
a he e ocyclic p ima y amide such as nico inamide and ac i-
a ed 4-( iuo ome hyl)benzamide affo ded mode a e o good
con e sion (50–65%) wi h high selec i i y.
Apa om a oma ic and alipha ic amides also he pa en
o mamides including alkyl o mamides such as N-oc yl o ma-
mide (Table 4, en y 4) o N-cyclohexyl o mamide (Table 4, en y
5) a e smoo hly hyd ogena ed unde he p e iously op imized
condi ions. E en using lowe ca alys loadings (1 mol% o Mn),
ull con e sion was ob ained (Table 4, en y 2). To show he
applicabili y o ou PNN pince complex Mn-2 nally hyd oge-
na ion o he he bicide diu enican was in es iga ed (Scheme 5).
Fo he s ime, his he bicide could be ca aly ically hyd oge-
na ed o he co esponding alcohol and amine unde ela i ely
mild condi ions affo ding good con e sion.
In o de o check he selec i i y o he Mn-2 pince complex,
hyd ogena ions o benchma kamidesin hep esenceo
addi ional educible g oups like ca bama e o u ea we e
ca ied ou (Scheme 6). To ou deligh , using ca alys Mn-2
highly selec i e educ ion o benzanilide 2and N-ace yl-
1,2,3,4- e ahyd oquinoline o he co esponding alcohols
Table 4 Hyd ogena ion o diffe en o mamides o he co esponding amines and me hanol ca alyzed by Mn-2 complex
En y
a
Fo mamide Con .
b
(%) Yield o amine
b
(%) Yield o alcohol
b
(%)
1>99 95 90
2
c
>99 92 88
390 85 80
483 83 80
5>99 >99 >99
6
d
>99 >99 >99
7
e
>99 >99 >99
a
S anda d eac ion condi ions: o mamide (0.25 mmol), Mn-2 ca . (2.37 mg, 0.005 mmol, 2 mol%), KO
Bu (2.8 mg, 0.025 mmol, 10 mol%),
cyclohexane (2 mL), 30 ba o H
2
, 100 C o e 16 h.
b
Con e sion o he o mamide and yield o he amine and me hanol we e calcula ed by GC
using hexadecane as ex e nal s anda d.
c
The eac ion was ca ied ou wi h 1 mol% o ca alys .
d
The eac ion was ca ied ou wi h 3 mol% o
ca alys .
e
The eac ion was ca ied ou a 120 C.
3582 |Chem. Sci.,2017,8, 3576–3585 This jou nal is © The Royal Socie y o Chemis y 2017
Chemical Science Edge A icle
Open Access A icle. Published on 08 Ma ch 2017. Downloaded on 1/7/2025 4:27:29 PM.
This a icle is licensed unde a
C ea i e Commons A ibu ion 3.0 Unpo ed Licence.
View A icle Online
and amines can be pe o med in he p esence o bo h e -
bu yl-N-me hylca bama e (Scheme 6, eqn (a) and (c)) o N,N-
diphenylu ea (Scheme 6, eqn (b) o (d)). I is no ewo hy, ha
hese esul s pa e he way owa ds selec i e dep o ec ion
s a egies in o ganic syn hesis media ed by his NNP pince
complex.
Conclusions
Diffe en well-dened manganese–PNN pince complexes ha e
been syn he ized o he s ime. One o hese complexes Mn-2
ca alyses efficien ly he selec i e hyd ogena ion o a wide ange o
amides o he co esponding alcohols and amines unde ela i ely
mild condi ions. Ac i a ed and non-ac i a ed seconda y and
e ia y amides and he mo e challenging p ima y amides can be
hyd ogena ed o he co esponding p oduc s in high yields. To
highligh he e sa ili y o he p o ocol, he educ ion o a mo e
complex amide such as diu enican is also included. To he bes
o ou knowledge, his is he s example o Mn-ca alyzed
hyd ogena ion o amides. Diffe en hyd ogena ion expe imen s
ha e shown he excellen selec i i y o he new manganese pince
complex o he hyd ogena ion o amides in he p esence o o he
educible g oups. This ac opens he doo o he po en ial
applica ion o his ype o ea h-abundan me al pince complexes
in o ganic syn he ic dep o ec ion me hodologies.
Expe imen al de ails
Gene al p ocedu e o he hyd ogena ion o amides
A 4 mL glass ial con aining a s i ing ba was sequen ially
cha ged unde a gon wi h amide (0.25 mmol) and complex Mn-
2(1–7 mol%). Ae wa ds, he eac ion ial was capped wi h
a sep um equipped wi h a sy inge needle and se in he alloy
pla e and he ial was pu ged wi h 3 cycles o acuum and
a gon. Cyclohexane o cyclohexane/ -amyl alcohol (1.5/0.5)
mix u e (2 mL) and he co esponding ca aly ic amoun o
KO
Bu we e sequen ially added unde a gon and he ial was
hen placed in o a 300 mL au ocla e. Once sealed, he au ocla e
was pu ged h ee imes wi h 20 ba o hyd ogen, hen p essu -
ized o he desi ed hyd ogen p essu e (30–50 ba ), and placed
in o an aluminum block ha was p ehea ed o he desi ed
empe a u e (80–140 C). Ae he desi ed eac ion ime o
16–48 h, he au ocla e was cooled in an ice ba h and he
emaining gas was ca e ully eleased. Finally, n-hexadecane
(20 mg) was added as an ex e nal s anda d, and he eac ion
mix u e was dilu ed wi h e hyl ace a e and analyzed by gas
ch oma og aphy.
Acknowledgemen s
We hank he s a e o Mecklenbu g-Vo pomme n and he BMBF
o nancial suppo . We would like also o hank he excellen
echnical and analy ical s affo he LIKAT o hei suppo . The
au ho s would like o dedica e his wo k o P o esso F ancesco
Ruffo, “Uni e si ´
a degli S udi di Napoli Fede ico II”and hank
D Rosa Adam O ´
ız o he in ense exchange o ideas ega ding
his p ojec .
No es and e e ences
1(a) P. Roose, K. Elle , E. Henkes, R. Rossbache and H. H¨
oke,
Ullmann's Encyclopedia o indus ial Chemis y, Ge many,
2000; (b) P. G. Jessop, The handbook o homogeneous
hyd ogena ion, Ge many, 2006.
2 Fo selec ed examples o ca boxylic acid de i a i es
hyd ogena ion, see: (a) S. We kmeis e , K. Junge, B. Wend ,
E. Albe ico, H. J. Jiao, W. Baumann, H. Junge, F. Gallou
and M. Belle , Angew. Chem., In . Ed., 2014, 53, 8722–8726;
Scheme 5 Selec i e hyd ogena ion o diflu enican o he co e-
sponding alcohol and amine ca alyzed by Mn-2 complex. Reac ion
condi ions: diflu enican (98.6 mg, 0.25 mmol), Mn-2 ca . (5.92 mg,
0.0125 mmol, 5 mol%), KO
Bu (2.8 mg, 0.025 mmol, 10 mol%),
cyclohexane (2 mL), 30 ba o H
2
, 130 C o e 16 h.
a
Con e sion o
amide and yield o amine was calcula ed by GC using hexadecane as
ex e nal s anda d.
b
The yield was calcula ed by
1
H NMR using 1,3,5-
ime hoxybenzene as ex e nal s anda d.
Scheme 6 Mn-ca alyzed selec i e hyd ogena ions o benzanilide 2
and N-ace yl-1,2,3,4- e ahyd oquinoline in he p esence o e -
bu yl-N-me hylca bama e (a) and (c) o diphenyl u ea (b) and (d).
S anda d eac ion condi ions: subs a e (0.25 mmol each one), Mn-2
ca . (2.37 mg, 0.005 mmol, 2 mol%), KO
Bu (2.8 mg, 0.025 mmol, 10
mol%), cyclohexane (2 mL), 30 ba o H
2
, 100 C o e 16 h. Con e sion
o he s a ing ma e ial and yield o he p oduc s we e calcula ed by
GC using hexadecane as ex e nal s anda d.
This jou nal is © The Royal Socie y o Chemis y 2017 Chem. Sci.,2017,8, 3576–3585 | 3583
Edge A icle Chemical Science
Open Access A icle. Published on 08 Ma ch 2017. Downloaded on 1/7/2025 4:27:29 PM.
This a icle is licensed unde a
C ea i e Commons A ibu ion 3.0 Unpo ed Licence.
View A icle Online
(b) T. om S ein, M. Meu esch, D. Limpe , M. Schmi z,
M. Holsche , J. Coe zee, D. J. Cole-Hamil on,
J. Klanke maye and W. Lei ne , J. Am. Chem. Soc., 2014,
136, 13217–13225; (c) D. S imani, A. Mukhe jee,
A. F. G. Goldbe g, G. Lei us, Y. Diskin-Posne ,
L. J. W. Shimon, Y. Ben Da id and D. Mils ein, Angew.
Chem., In . Ed., 2015, 54, 12357–12360; (d) X. J. Cui,
Y. H. Li, C. Top , K. Junge and M. Belle , Angew. Chem., In .
Ed., 2015, 54, 10596–10599; (e) T. J. Ko s anje, J. I. an de
Vlug , C. J. Else ie and B. de B uin, Science, 2015, 350,
298–301; ( ) M. Na u o and S. Sai o, Na . Commun., 2015, 6,
8140; (g) J. R. Cab e o-An onino, I. So ibes, K. Junge and
M. Belle , Angew. Chem., In . Ed., 2016, 55, 387–391.
3 Fo a gene al book abou o ganic educ ions, see: (a)
J. Seyden-Penne, Reduc ions by he Aumino- and
Bo ohyd ides in O ganic Syn hesis, Wiley, New Yo k, 2nd
edn, 1997, o selec ed examples, see: (b) S. Zhou,
K. Junge, D. Addis, S. Das and M. Belle , Angew. Chem., In .
Ed., 2009, 48, 9507–9510; (c) S. Das, D. Addis, S. L. Zhou,
K. Junge and M. Belle , J. Am. Chem. Soc., 2010, 132, 4971–
4971; (d) G. Pelle ie , W. S. Becha a and A. B. Cha e e, J.
Am. Chem. Soc., 2010, 132, 12817–12819; (e) S. Das,
D. Addis, K. Junge and M. Belle , Chem.–Eu . J., 2011, 17,
12186–12192; ( ) C. Cheng and M. B ookha , J. Am. Chem.
Soc., 2012, 134, 11304–11307; (g) S. Das, B. Wend ,
K. Molle , K. Junge and M. Belle , Angew. Chem., In . Ed.,
2012, 51, 1662–1666; (h) T. Domb ay, C. Helleu, C. Da cel
and J. B. So ais, Ad . Syn h. Ca al., 2013, 355, 3358–3362;
(i) S. Pa k and M. B ookha , J. Am. Chem. Soc., 2012, 134,
640–653; (j) J. T. Ree es, Z. L. Tan, M. A. Ma sini,
Z. X. S. Han, Y. B. Xu, D. C. Ree es, H. Lee, B. Z. Lu and
C. H. Senanayakea, Ad . Syn h. Ca al., 2013, 355,47–52; (k)
E. Blondiaux and T. Can a , Chem. Commun., 2014, 50,
9349–9352; (l) N. L. Lampland, M. Ho ey, D. Mukhe jee
and A. D. Sadow, ACS Ca al., 2015, 5, 4219–4226; (m)
D. Mukhe jee, S. Shi ase, K. Mashima and J. Okuda, Angew.
Chem., In . Ed., 2016, 55, 13326–13329; o a e iew abou
chemoselec i e educ ion o ca boxamides, see: (n)
A. Volko , F. Tinnis, T. S agb and, P. T illo and
H. Adol sson, Chem. Soc. Re ., 2016, 45, 6685–6697.
4(a) H. C. B own, S. Na asimhan and Y. M. Choi, Syn hesis,
1981, 441–442; (b) J. Ma ch, Ad anced O ganic Chemis y,
Wiley, New yo k, 4 h edn, 1992; (c) S. We kmeis e ,
K. Junge and M. Belle , O g. P ocess Res. De ., 2014, 18,
289–302.
5(a) P. A. Dub and T. Ika iya, ACS Ca al., 2012, 2, 1718–1741;
(b) D. L. Dodds and D. J. Cole-Hamil on, in Sus ainable
Ca alysis: Challenges and p ac ices o he Pha maceu ical
and Fine Chemical Indus ies, John Wiley and Sons,
Hoboken, NJ, 2013; (c) A. M. Smi h and R. Whyman, Chem.
Re ., 2014, 114, 5477–5510.
6(a) P. M. Rylande , Hyd ogena ion Me hods, Academic P ess,
London, 1985; (b) J. Ha wig, O gano ansi ion Me al
chemis y, Uni e si y Science Books, 2010.
7 D. Can illo, Eu . J. Ino g. Chem., 2011, 3008–3013.
8(a) J. H. Paden and H. Adkins, J. Am. Chem. Soc., 1936, 58,
2487; (b) J. C. Saue and H. Adkins, J. Am. Chem. Soc., 1938,
60, 402; (c) J. D. D'Ianni and H. Adkins, J. Am. Chem. Soc.,
1939, 61, 1675; (d) A. Guye , A. Biele and G. Ge liczy, Hel .
Chim. Ac a, 1955, 38, 1649; (e) H. S. B oadben and
W. J. Ba ley, J. O g. Chem., 1963, 28, 2345; ( ) I. A. Dobson,
Eu . Pa . Appl., EP0286280 A1, 1988; (g) C. Hi osawa,
N. Wakasa and T. Fuchikami, Te ahed on Le ., 1996, 37,
6749–6752; (h) A. A. Smi h, P. Dani, P. D. Higginson and
A. J. Pe man, PCT In . Appl., WO 2005066112 A1, 2005; (i)
G. Beamson, A. J. Papwo h, C. Philipps, A. M. Smi h and
R. Whyman, J. Ca al., 2010, 269,93–102; (j) G. Beamson,
A. J. Papwo h, C. Philipps, A. M. Smi h and R. Whyman,
Ad . Syn h. Ca al., 2010, 352, 869–883; (k) G. Beamson,
A. J. Papwo h, C. Philipps, A. M. Smi h and R. Whyman, J.
Ca al., 2011, 278, 228–238; (l) R. Bu ch, C. Paun, X. M. Cao,
P. C aw o d, P. Good ich, C. Ha dac e, P. Hu,
L. McLaughlin, J. Sa and J. M. Thompson, J. Ca al., 2011,
283,89–97; (m) J. Coe zee, H. G. Manya , C. Ha dac e and
D. J. Cole-Hamil on, ChemCa Chem, 2013, 5, 2843–2847; (n)
M. S ein and B. B ei , Angew. Chem., In . Ed., 2013, 52,
2231–2234.
9(a)A.A.N
´
u˜
nez Mag o, G. R. Eas ham and D. J. Cole-
Hamil on, Chem. Commun., 2007, 3154–3156; (b)
D. L. Dodds, J. Klanke maye , S. B osinski, W. Lei ne and
D. J. Cole-Hamil on, Chem. Commun., 2012, 48, 12249–
12262; (c) J. Coe zee, D. L. Dodds, J. Klanke maye ,
S. B osinski, W. Lei ne , A. M. Z. Slawin and D. J. Cole-
Hamil on, Chem.–Eu . J., 2013, 19, 11039–11050; (d)
J. R. Cab e o-An onino, E. Albe ico, K. Junge, H. Junge and
M. Belle , Chem. Sci., 2016, 7, 3432–3442; (e) M. L. Yuan,
J. H. Xie and Q. L. Zhou, ChemCa Chem, 2016, 8, 3036–3040.
10 M. L. Yuan, J. H. Xie, S. F. Zhu and Q. L. Zhou, ACS Ca al.,
2016, 6, 3665–3669.
11 (a) R. Noyo i, M. Yamakawa and S. Hashiguchi, J. O g. Chem.,
2001, 66, 7931–7944; (b) C. Gunana han and D. Mils ein, Acc.
Chem. Res., 2011, 44, 588–602; (c) S. Schneide , J. Meine s
and B. Aske old, Eu . J. Ino g. Chem., 2012, 412–429.
12 Fo Schwa z eagen -media ed educ ion o amides o
amines and aldehydes, see: (a) J. T. Sple s ose ,
J. M. Whi e, A. R. Tunoo i and G. I. Geo g, J. Am. Chem.
Soc., 2007, 129, 3408–3419; (b) E. Bala aman,
B. Gnanap akasam, L. J. W. Shimon and D. Mils ein, J. Am.
Chem. Soc., 2010, 132, 16756–16758; o SmI
2
-media ed
educ ion o amides by C–N bond clea age, see: (c)
M. Szos ak, M. Spain, A. J. Ebe ha and D. J. P oc e , J.
Am. Chem. Soc., 2014, 136, 2268–2271.
13 (a) M. I o, T. Oo suka, R. Wa a i, A. Shiibashi, A. Himizu and
T. Ika iya, J. Am. Chem. Soc., 2011, 133, 4240–4242; (b)
J. M. John and S. H. Be gens, Angew. Chem., In . Ed., 2011,
50, 10377–10380; (c) T. Miu a, I. E. Held, S. Oishi,
M. Na u o and S. Sai o, Te ahed on Le ., 2013, 54, 2674–
2678; (d) Y. Ki a, T. Higuchi and K. Mashima, Chem.
Commun., 2014, 50, 11211–11213; (e) J. M. John,
R. Loo hu aja, E. An oniuk and S. H. Be gens, Ca al. Sci.
Technol., 2015, 5, 1181–1186; ( ) L. Shi, X. Tan, J. Long,
X. Xiong, S. Yang, P. Xue, H. L and X. Zhang, Chem.–Eu .
J., 2017, 23, 546–548; (g) J. R. Cab e o-An onino, E. Abe ico,
3584 |Chem. Sci.,2017,8, 3576–3585 This jou nal is © The Royal Socie y o Chemis y 2017
Chemical Science Edge A icle
Open Access A icle. Published on 08 Ma ch 2017. Downloaded on 1/7/2025 4:27:29 PM.
This a icle is licensed unde a
C ea i e Commons A ibu ion 3.0 Unpo ed Licence.
View A icle Online