Conjugate reduction of α,β-unsaturated carbonyl and carboxyl compounds with poly(methylhydrosiloxane) catalyzed by a silica-supported compact phosphane-copper complex

Article abstract of DOI:10.1002/adsc.201200555

A silica-supported, cage-type, compact phosphane (Silica-SMAP) was used for the copper-catalyzed conjugate reduction of α,β-unsaturated carbonyl and carboxyl compounds with poly(methylhydrosiloxane) (PMHS). The heterogeneous catalyst system showed high activity and chemoselectivity, and was easily separable from the reaction mixture after the reaction. Furthermore, the catalyst was reusable without loss of its high catalytic activity or selectivity.

Full text of DOI:10.1002/adsc.201200555

COMMUNICATIONS
DOI: 10.1002/adsc.201200555
Conjugate Reduction of a,b-Unsaturated Carbonyl and Carboxyl
Compounds with Poly(methylhydrosiloxane) Catalyzed by
a Silica-Supported Compact Phosphane–Copper Complex
Soichiro Kawamorita,a Kenji Yamazaki,a Hirohisa Ohmiya,a Tomohiro Iwai,a
and Masaya Sawamuraa,*
a
Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan
Fax : +(81)-11-706-3449; phone: +(81)-11-706-3434; e-mail: sawamura@sci.hokudai.ac.jp
Received: June 25, 2012; Revised: August 29, 2012; Published online: November 28, 2012
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200555.
Abstract: A silica-supported, cage-type, compact
phosphane (Silica-SMAP) was used for the copper-
catalyzed conjugate reduction of a,b-unsaturated
carbonyl and carboxyl compounds with poly(me-
thylhydrosiloxane) (PMHS). The heterogeneous
catalyst system showed high activity and chemose-
lectivity, and was easily separable from the reaction
mixture after the reaction. Furthermore, the cata-
lyst was reusable without loss of its high catalytic
activity or selectivity.
phane,[4,5] and showed this ligand to be useful for
forming coordinatively unsaturated mono(phos-
phane)–metal (P/M 1:1) species in Rh, Ir, and Pd cat-
alysis. Based on this knowledge, we then expected
that an active copper(I) hydride species coordinated
with a single monodentate phosphane ligand could be
formed using Silica-SMAP.
Herein, we report that a Silica-SMAP-Cu system
showed high activities for the conjugate reduction of
a,b-unsaturated carbonyl and carboxyl (ester, amide,
and nitrile) compounds with PMHS. Applicability
toward sterically demanding and challenging sub-
strates is a notable feature of the catalysis with Silica-
SMAP. Additionally, the heterogeneous nature al-
lowed the relatively easy recovery and reuse of the
catalyst.
Keywords: conjugate reduction; copper catalysts;
heterogeneous catalysis; immobilized ligands
The reduction of isophorone (1a, 5.0 mmol) with
The copper-catalyzed conjugate reduction of a,b-un- PMHS (2, 3.0 equiv.) in t-BuOH[6] in the presence of
saturated carbonyl and carboxyl compounds with hy- CuACHTUNGRTENUNG(OAc)2·H2O (0.02 mol%) and Silica-SMAP
drosilanes is a useful transformation in organic syn- (0.02 mol%) proceeded at room temperature to give
thesis, because of its mild reaction conditions and ex- the corresponding saturated ketone (3a) in 86% yield
cellent chemoselectivity.[1,2] Generally, phosphane-co- without forming a carbonyl reduction product [Eq.
ordinated hexameric copper hydride [CuHACTHNUTRGNEUNG
(PPh3)]6, (1)].[7] It is noteworthy that a basic work-up was not
so-called “Strykerꢀs reagent”, and in-situ generated necessary after the reaction in the present system;
Cu H species with phosphane or N-heterocyclic car- crude material was obtained only by filtration.[8]
À
bene ligands are used as a catalyst.[3] Lipshutz and co-
workers introduced 1,2-bis(diphenylphosphino)ben-
zene (o-BDPPB, shortened herein to BDP) as an
achiral ligand that shows exceptionally high perfor-
mance in the reactions with poly(methyhydrosilox-
ane) (PMHS) as a stoichiometric hydride source.
Prior to this work, Lipshutzꢀs group had shown
DTBM-SEGPHOS[3g,h,i,k] to be an excellent chiral
ligand for an enantioselective version. In these stud-
ies, the formation of 16-electron monomeric species
with a bidentate phosphane, (bisphosphane)CuH, was
proposed. On the other hand, we developed Silica-
SMAP, a silica-supported, monodentate trialkylphos-
3440
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 3440 – 3444

Conjugate Reduction of a,b-Unsaturated Carbonyl and Carboxyl Compounds
Table 1. Ligand effect in the Cu-catalyzed conjugate reduc-
tion of isophorone 1a.[a]
Next, Silica-SMAP-Cu was used for the conjugate
reduction of various a,b-unsaturated carboxylic acid
derivatives (1b–d), and the same series of reactions
were conducted with the BDP ligand for comparison.
Results are summarized in Table 2.[11] Note that the
basic work-up was not necessary for all of the entries
listed in this table irrespective of the ligands used.
The reductions of benzyl acrylate (1b) and b-t-Bu-
substituted benzyl acrylate 1c proceeded in good
yields with both ligands (entries 1–4). Allyl cinnamate
1d was a suitable substrate despite having a potentially
reactive allyl ester moiety (entries 5 and 6). Substitut-
ed acrylonitrile derivative 1e underwent a clean con-
jugate reduction to give saturated nitrile 3e (entries 7
and 8).
The advantage of using Silica-SMAP-Cu over BDP-
Cu was clearly observed in the reduction of a,b-unsa-
turated amide 1f. While the former gave a complete
conjugate reduction, the latter induced only a 64%
substrate conversion (Table 2, entries 9 and 10).
Moreover, Silica-SMAP exhibited a superior ligand
effect in the reaction of tetrasubstituted alkene sub-
strate 1g, which is a challenging substrate due to its
steric demands (entries 11 and 12). It seems that the
compact nature of the Silica-SMAP ligand was benefi-
cial for the reaction of the sterically demanding sub-
strate.[5a,b,c,g] In addition, the conjugate reduction of
alkynoate 1h to give the corresponding saturated
ester (3h) was successful with Silica-SMAP-Cu, while
BDP-Cu induced only a low substrate conversion (en-
tries 13 and 14).
Entry
Ligand
Cu/P
GC Yield[b] [%]
1
2
3
4
5
6
7
8
Silica-SMAP
Ph-SMAP
Ph-SMAP
Ph3P
Ph3P
Me3P
Me3P
T
N
E
1:1
1:1
1:2
1:1
1:2
1:1
1:2
1:1
1:2
1:1
1:2
1:1
1:2
1:2
1:2
1:2
1:2
–
96
0
1
8
7
1
1
5
5
9
10
11
12
13
14
15
16
17
18
1
1
A
Cy3P
Cy3P
dppe
dppp
Xantphos
BDP
none
22
22
6
11
1
14
0
[a]
The reaction was carried out with isophorone 1a
(0.5 mmol), PMHS (3 equiv., 1.5 mmol),
Cu(OAc)2·H2O (0.5 mol%), phosphane ligand (0.5 or
2
ACHTUNGTRENNUNG
1.0 mol%), t-BuOH (3 equiv., 1.5 mmol) in THF
(0.5 mL) at room temperature for 1 h.
GC yield based on 1a. Dibenzyl was used as internal
standard.
[b]
The Silica-SMAP-Cu heterogeneous catalyst was
easily separated from the reaction mixture by decant-
ation or Celiteꢂ filtration. Additionally, the catalyst
was reusable for the reduction of (E)-benzyl but-2-
To investigate the rate accelerating effect, various enoate 1i: the catalyst at 0.5 mol% loading was used
ligands were examined in the reduction of isophorone three times without detection of a decrease in the ac-
1a with PMHS at room temperature for 1 h with tivity (Table 3).
0.5 mol% of Cu
G
To investigate the nature of interactions between
SMAP-Cu system afforded 3a in 96% GC yield Silica-SMAP and Cu species in the reaction system,
(entry 1).[9] Interestingly, the corresponding homoge- 31P CP-MAS-NMR measurements of solid phases
neous catalysts that were prepared in-situ from were conducted before and after the catalytic reaction
CuACHTUNGTRENNUNG(OAc)2·H2O and Ph-SMAP (0.5 mol% Cu, 1:1 or with isophorone (1a) (Figure 1, a and b, respectively).
1:2 Cu/P) afforded only a trace amount of the product To obtain the spectrum of the sample before the cat-
(entries 2 and 3), indicating that immobilization of the alysis, Silica-SMAP (0.036 mmol P) was treated with
phosphane is crucial. Other commonly used mono- CuACHTUNTRGNEUNG(OAc)2·H2O (1 equiv.), PMHS (50 equiv.), and t-
phosphane and bisphosphane ligands also gave only BuOH (50 equiv.) in THF (1.0 mL) at room tempera-
low conversions (entries 4–16). Notably, BDP was not ture for 20 min, and the resulting dry solid was used
effective under these conditions using THF as solvent for the measurement. On the other hand, in order to
(entry 17).[10] No reaction occurred without a phos- obtain the spectrum of the sample after the catalysis,
phane ligand (entry 18). These experiments demon- procedures similar to the ones mentioned above were
strated excellent ligand performance of immobilized followed: 1a (10 equiv.) was added and the resulting
compact monophosphane Silica-SMAP and indicate mixture was allowed to react for 1 h. Even though the
that the steric bulkiness and rigid backbone are not loading ratio of P and Cu was 1:1, a signal corre-
essential factors for the ligand to promote the Cu-cat- sponding to free Silica-SMAP (À58.8 ppm) was ob-
alyzed conjugate reduction efficiently.
served together with a minor signal assignable to the
phosphane-coordinated copper species in the lower
Adv. Synth. Catal. 2012, 354, 3440 – 3444
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3441

Soichiro Kawamorita et al.
COMMUNICATIONS
Table 2. Conjugate reduction of various a,b-unsaturated carboxylic acid derivatives with Silica-SMAP-Cu and BDP-Cu sys-
tems.[a]
Entry
Substrate 1
Product 3
Ligand
Conv. [%]
Yield[b] [%]
1
2
Silica-SMAP
BDP
100
100
83
(99)
3
4
Silica-SMAP
BDP
100
100
84
(99)
5
6
Silica-SMAP
BDP
100
93
92
(93)
7
8
Silica-SMAP
BDP
100
100
85
(99)
9
10
Silica-SMAP
BDP
100
64
88
(64)
11
12
Silica-SMAP
BDP
100
9
94
(9)
13
14
Silica-SMAP
BDP
100
19
79
(6)
[a]
The reaction was carried out with 1 (0.5 mmol), PMHS 2 (3 equiv., 1.5 mmol), CuACTHNUTRGNE(UNG OAc)2·H2O (0.5 mol%), ligand
(0.5 mol%), t-BuOH (3 equiv., 1.5 mmol) at room temperature. THF (0.5 mL) was used as solvent in Silica-SMAP
system, and toluene (0.5 mL) was used in BDP system.
Isolated yield. NMR yield is in parentheses.
[b]
Table 3. Reusability of Silica-SMAP-Cu in the conjugate re-
In summary, a silica-supported compact phosphane-
Cu complex Silica-SMAP-Cu showed high activities
for the conjugate reduction of various a,b-unsaturated
carbonyl compounds with PMHS. This work demon-
strated that the immobilization to a silica gel surface
was critical for excellent ligand performance of the
compact monodentate phosphane. The work also indi-
cated that the use of bidentate phosphane ligands
with sterically demanding P-substituents or a rigid
backbone is not always necessary to prepare effective
catalysts. The Silica-SMAP-Cu heterogeneous catalyst
was easily separated and reusable. This is the first
demonstration that Silica-SMAP is useful for copper
catalysis.
duction of 1i.[a]
Cycle
GC conv. [%]
NMR yield [%]
1
2
3
100
100
100
96
99
99
[a]
The reaction was carried out with 1i (0.5 mmol), PMHS 2
(3 equiv., 1.5 mmol), Cu(OAc)2·H2O (0.5 mol%), Silica-
AHCTUNGTRENNUNG
SMAP (0.5 mol%), t-BuOH (3 equiv., 1.5 mmol) in THF
(0.5 mL) at room temperature for 2 h with shaking.
Experimental Section
magnetic field region (À28.1 ppm) in both samples.
These results indicate that only part of the SMAP
moiety of Silica-SMAP is associated with the coordi-
nation to Cu, causing the catalytic activity observed in
the present system. Although the complicated CP-
MAS-NMR spectra do not provide the distinct struc-
ture of a catalytically active species, we assume that
Silica-SMAP can produce a monomeric 1:1 Cu–P spe-
cies regardless of its compact steric nature to achieve
a high degree of coordinative unsaturation of the
copper because efficient site isolation of the P-center
is realized on the silica surface.[5a,b]
Typical Procedure for Conjugate Reduction of
Isophorone (1a) (Table 1, Entry 1)
In a glove box, Silica-SMAP (0.063 mmol PgÀ1, 40 mg,
0.0025 mmol) and an internal standard (dibenzyl) were
placed in a 10-mL glass tube containing a magnetic stirring
bar. Then CuACTHNUTRGNE(UNG OAc)2·H2O (0.5 mg, 0.0025 mmol) in THF
(0.5 mL) and t-BuOH (111.2 mg, 1.5 mmol) were added to
the tube. The mixture was stirred for 1 min at room temper-
ature. PMHS (2, 90.2 mg, 1.5 mmol) was added to the tube,
and the mixture was stirred for 5 min. Isophorone (1a,
69.1 mg 0.5 mmol) was added to the tube, which was then
sealed with a screw cap. The tube was removed from the
3442
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 3440 – 3444

Conjugate Reduction of a,b-Unsaturated Carbonyl and Carboxyl Compounds
References
[1] B. H. Lipshutz, in: Modern Organocopper Chemistry,
(Ed.: N. Krause), Wiley-VCH, Weinheim, 2002,
pp. 167–187.
[2] For reviews on copper catalyzed conjugate reduction,
see: a) S. Rendler, M. Oestreich, Angew. Chem. 2007,
119, 504–510; Angew. Chem. Int. Ed. 2007, 46, 498–504;
b) C. Deutsch, N. Krause, B. H. Lipshutz, Chem. Rev.
2008. 108, 2916–2927; c) B. H. Lipshutz, Synlett 2009,
509–524.
[3] For selected references on Cu-catalyzed 1,4-reduction
of a,b-unsaturated carbonyl compounds with hydrosi-
lane, see: a) A. Mori, A. Fujita, Y. Nishihara, T.
Hiyama, Chem. Commun. 1997, 2159–2160; b) H. Ito,
T. Ishizuka, K. Arimoto, K. Miura, A. Hosomi, Tetrahe-
dron Lett. 1997, 38, 8887–8890; c) B. H. Lipshutz, J.
Keith, P. Papa, R. Vivian, Tetrahedron Lett. 1998, 39,
4627–4630; d) D. H. Appella, Y. Moritani, R. Shintani,
E. M. Ferreira, S. L. Buchwald, J. Am. Chem. Soc.
1999. 121, 9473–9474; e) B. H. Lipshutz, W. Chrisman,
K. Noson, P. Papa, J. A. Sclafani, R. W. Vivian, J. M.
Keith, Tetrahedron 2000, 56, 2779–2788; f) V. Jurkaus-
kas, J. P. Sadighi, S. L. Buchwald, Org. Lett. 2003, 5,
2417–2420; g) B. H. Lipshutz, J. M. Servesko, Angew.
Chem. 2003, 115, 4937–4940.; Angew. Chem. Int. Ed.
2003, 42, 4789–4792; h) B. H. Lipshutz, J. M. Servesko,
B. R. Taft, J. Am. Chem. Soc. 2004, 126, 8352–8353;
i) B. H. Lipshutz, J. M. Servesko, T. B. Petersen, P. P.
Papa, A. A. Lover, Org. Lett. 2004, 6, 1273–1275;
j) M. P. Rainka, J. E. Milne, S. L. Buchwald, Angew.
Chem. 2005, 117, 6333–6336; Angew. Chem. Int. Ed.
2005, 44, 6177–6180; k) B. H. Lipshutz, B. A. Frieman,
Angew. Chem. 2005, 117, 6503–6506.; Angew. Chem.
Int. Ed. 2005, 44, 6345–6348; l) D. Lee, D. Kim, J. Yun,
Angew. Chem. 2006, 118, 2851–2853; Angew. Chem.
Int. Ed. 2006, 45, 2785–2787; m) T. Llamas, R. G.
Arrayꢃs, J. C. Carretero, Angew. Chem. 2007, 119,
3393–3396; Angew. Chem. Int. Ed. 2007, 46, 3329–3332;
ˇ
Figure 1. 31P CP-MAS-NMR spectra of Silica-SMAP-Cu
system (a) before and (b) after the catalytic reaction with
1a. See text and the Supporting Information for details.
ˇ
´
n) B. A. Baker, Z. V. Boskovic, B. H. Lipshutz, Org.
Lett. 2008, 10, 289–292; o) L. Rupnicki, A. Saxena,
H. W. Lam, J. Am. Chem. Soc. 2009, 131, 10386–10387.
[4] SMAP (silicon-constrained monodentate trialkylphos-
phane): a) A. Ochida, K. Hara, H. Ito, M. Sawamura,
Org. Lett. 2003, 5, 2671–2674; b) A. Ochida, S. Ito, T.
Miyahara, H. Ito, M. Sawamura, Chem. Lett. 2006, 35,
294–295; c) A. Ochida, G. Hamasaka, Y. Yamauchi, S.
Kawamorita, N. Oshima, K. Hara, H. Ohmiya, M. Sa-
wamura, Organometallics 2008, 27, 5494–5503; d) K.
Hara, R. Akiyama, S. Takakusagi, K. Uosaki, T. Yoshi-
no, H. Kagi, M. Sawamura, Angew. Chem. 2008, 120,
5709–5712; Angew. Chem. Int. Ed. 2008, 47, 5627–5630.
[5] For the synthesis and applications of Silica-SMAP, see:
a) G. Hamasaka, A. Ochida, K. Hara, M. Sawamura,
Angew. Chem. 2007, 119, 5477–5479; Angew. Chem.
Int. Ed. 2007, 46, 5381–5383; b) G. Hamasaka, S. Kawa-
morita, A. Ochida, R. Akiyama, K. Hara, A. Fukuoka,
K. Asakura, W. J. Chun, H. Ohmiya, M. Sawamura, Or-
ganometallics 2008, 27, 6495–6506; c) S. Kawamorita,
G. Hamasaka, H. Ohmiya, K. Hara, A. Fukuoka, M.
Sawamura, Org. Lett. 2008, 10, 4697–4700; d) S. Kawa-
morita, H. Ohmiya, K. Hara, A. Fukuoka, M. Sawa-
glove box. The resulting mixture was stirred at room tem-
perature for 1 h. After the reaction, the yield of the product
3a was determined by gas chromatography.
Acknowledgements
This work was supported by Grants-in-Aid for Scientific Re-
search on Innovative Areas “Organic Synthesis Based on Re-
action Integration” and a Global COE grant (YProject No.
B01: Catalysis as the Basis for Innovation in Materials Sci-
ence) from MEXT, and by CREST from JST. S.K. thanks
JSPS for scholarship support.
Adv. Synth. Catal. 2012, 354, 3440 – 3444
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3443

Soichiro Kawamorita et al.
COMMUNICATIONS
mura, J. Am. Chem. Soc. 2009, 131, 5058–5059; e) S.
Kawamorita, H. Ohmiya, M. Sawamura, J. Org. Chem.
2010, 75, 3855–3858; f) K. Yamazaki, S. Kawamorita,
H. Ohmiya, M. Sawamura, Org. Lett. 2010, 12, 3978–
3981; g) S. Kawamorita, H. Ohmiya, T. Iwai, M. Sawa-
mura, Angew. Chem. 2011, 123, 8513–8516; Angew.
Chem. Int. Ed. 2011, 50, 8363–8366; h) S. Kawamorita,
M. Tatsuya, H. Ohmiya, T. Iwai, M. Sawamura, J. Am.
Chem. Soc. 2011, 133, 19310–19313.
the products, especially when the substrate is a ketone
and the reductant is PMHS (see refs.[3g,3i,3k,3n]).
[9] Conjugate reduction of 1a with Ph2SiH2 (1.2 equiv.) in
the
presence
of
Silica-SMAP
(1 mol%),
(CuOTf)2·toluene (0.5 mol%), and t-BuOK (6 mol%)
in THF at room temperature for 4 h afforded 3a in
98% yield (GC, work-up with 2M aqueous NaOH).
[10] Lipshutz reported that the BDP-Cu system was effec-
tive for reduction of isophorone 1a in toluene, and that
THF was not a suitable solvent (see ref.[3n]). We con-
firmed that the reduction of 1a with the BDP-Cu
system proceeded in toluene with a full conversion of
1a; however, 3a was obtained in only a low yield (29%)
after the neutral work-up.
À
[6] t-BuOH was added to enhance the generation of Cu
H. The Cu-enolate intermediate could be protonated
À
by t-BuOH to generate t-BuO Cu, which is more
active to transmetalate with hydrosilane.
[7] Lipshutz reported that CuCl and DTBM-SEGPHOS
system is highly active, and the asymmetric reduction
of isophorone 1a proceeded with 1 mol% of CuCl and
0.00036 mol% of ligand (see ref.[3i]).
[8] In other reported bisphosphane systems, work-up
under the strongly basic conditions is needed to obtain
[11] THF was used as solvent in Silica-SMAP system, and
toluene was used as solvent in BDP-Cu system accord-
ing to the original report (see ref.[3n]).
3444
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 3440 – 3444