Polymer-immobilized α,α-bis[bis-3,5-(trifluoromethyl)phenyl]prolinol silyl ether: Synthesis and application in the asymmetric α-amination of aldehydes

Article abstract of DOI:10.1016/j.mencom.2015.11.002

α,α-Bis[bis-3,5-(trifluoromethyl)phenyl]prolinol silyl ether anchored onto polystyrene was synthesized and tested in asymmetric α-amination of aldehydes. The catalytic activity and enantioselectivity of the immobilized catalyst persist for 3 cycles.

Full text of DOI:10.1016/j.mencom.2015.11.002

Mendeleev
Communications
Mendeleev Commun., 2015, 25, 410–411
Polymer-immobilized a,a-bis[bis-3,5-(trifluoromethyl)phenyl]prolinol silyl
ether: synthesis and application in the asymmetric a-amination of aldehydes
Anton A. Guryev, Maksim V. Anokhin, Alexei D. Averin and Irina P. Beletskaya*
Department of Chemistry, M. V. Lomonosov Moscow State University, 119991 Moscow, Russian Federation.
Fax: +7 495 939 1139; e-mail: beletska@org.chem.msu.ru
DOI: 10.1016/j.mencom.2015.11.002
a,a-Bis[bis-3,5-(trifluoromethyl)phenyl]prolinol silyl ether anchored onto polystyrene was synthesized and tested in asymmetric
a-amination of aldehydes. The catalytic activity and enantioselectivity of the immobilized catalyst persist for 3 cycles.
Chiral amino carbonyl compounds and amino alcohols are
HO
HO
important for the synthesis of biologically active molecules and
medicines.1 Direct enantioselective a-amination of carbonyl com-
pounds is the most efficient route to such molecules.2 After
pioneer works by List3 and Jørgensen4 a-amination of aldehydes
and ketones with azodicarboxylates catalyzed by l-proline was
used as a key step in the synthesis of valuable chiral compounds.
Among them are (S,S)-ethambutol5 and (–)-anisomycin6 anti-
biotics, (R)-selegiline,7 known as a remedy against Parkinson’s
disease, (–)-d-coniceine alkaloid.8 In the further works this reac-
tion was carried out in the presence of more sophisticated organo-
catalysts including derivatives of trans-4-hydroxy-l-proline,9–11
pyrrolidine-tetrazole,12 quinine derivatives,13 binaphthylphos-
phonium14 and binaphthylammonium salts.15,16 Silyl ethers of
diarylprolinols are perspective catalysts of such processes,17,18 they
helped to achieve high yields and enantiomeric excess. A draw-
back of these catalysts is high catalyst loading (10–20 mol%).
The problem can be solved by the immobilization of proline-
based catalysts on the support,19–22 that provides an easy separa-
tion after the completion of the reaction, repeated use of the
catalyst and increases the efficiency of the process (TON).
We carried out the immobilization of diarylprolinol catalyst
on Merrifield resin23,24 using simple and reliable click-reac-
tion.25,26 A clickable derivative of prolinol 4 was synthesized via
a 3-step procedure (Scheme 1) in an overall 83% yield. At the
first step N-Boc derivative of trans-4-hydroxy-l-proline 1 was
reacted with 3,5-bis(trifluoromethyl)phenylmagnesium bromide
at –78°C. The yield of a,a-diaryl-4-hydroxyprolinol 2 was 92%
after purification by column chromatography. Acylation was
employed to introduce a substituent containing triple bond into
compound 2, 4-propargyloxybenzoic acid being used as a linker
for immobilization. The synthesis was carried out in the presence
of DCC and catalytic amount of DMAP and compound 3 was
isolated after purification by column chromatography in 95% yield.
Simultaneous Boc-deprotection and silylation were achieved by
the reaction with TMSOTf and preparative yield of clickable
organocatalyst 4 was 95%. The click-reaction of prolinol 4 and
azidopolystyrene was run in the presence of 10 mol% CuI and
{tris[(1-tert-butyl-1H-1,2,3-triazol-4-yl)methyl]amine} (TTTA)27
taken as ligand. The reaction was monitored by IR spectroscopy
and the completion of the reaction was evidenced by the absence
of the absorption band at 2090 cm–1 corresponding to azido
group and by the emergence of an absorption band at 1716 cm–1
corresponding to the carbonyl group of the linker. Heterogeneous
catalyst 5 was isolated by filtration, trace amounts of copper were
removed by the treatment with 8-hydroxyquinoline in THF till
solution became colorless. After prolonged drying in vacuo the
ii
i
Ar
Ar
OH
COOMe
N
N
Boc
Boc
1
2, 92%
Ar = 3,5-(CF3)2C6H3
O
O
iii
O
O
O
O
Ar
Ar
OH
Ar
Ar
OTMS
N
Boc
N
H
3, 95%
4, 95%
O
N
N
iv
N
O
O
PS
Ar
Ar
OTMS
N
H
5
Scheme 1 Reagents and conditions: i, 3,5-(CF3)2C6H3MgBr, THF, –78°C,
12 h; ii, 4-HCºCCH2OC6H4CO2H, DCC, DMAP, DCM, 4°C, 72 h; iii,
TMSOTf, TEA, DCM, 4°C, 24 h; iv, azidopolystyrene, 10 mol% CuI, 10 mol%
TTTA, THF–DMF, 50°C, 24 h (see Online Supplementary Materials).
loading of the polymer catalyst was verified by the elemental
analysis.
Catalytic activity of the new immobilized organocatalyst in
a-amination was investigated using convenient aliphatic aldehydes.
To prevent an easy racemization, the obtained a-hydrazo aldehydes
were reduced with NaBH4 in situ to obtain the corresponding
a-hydrazo alcohols. As the catalyst decomposes in the course of
prolonged reactions, microwave irradiation of minimal power
(1 W, T < 30°C) and at maximal stirring (600 rpm) rate for 8 h
were employed under neat conditions. The results are summarized
in Table 1.
Though the chemical yields were high, enantioselectivity was
poor in the reaction with diethyl azodicarboxylates (entries 1, 2).
The use of a less reactive dibenzyl azodicarboxylate diminished
preparative yields of a-hydrazo alcohols 6c and 6d (43 and 55%,
respectively), while their enantiomeric purity increased significantly
(over 99% ee, entries 3, 4).
© 2015 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
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Mendeleev Commun., 2015, 25, 410–411
Table 1 Enantioselective a-amination of aldehydes catalyzed by 5.
i, cat. 5, 20 mol%
This work was supported by the Russian Science Foundation
(grant no. 14-23-00186).
COOR2
COOR2
O
COOR2
MW (1 W), 8 h
ii, NaBH4, EtOH
Online Supplementary Materials
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2015.11.002.
N
N
N
HO
N
COOR2
H
R1
R1
6a–d
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R1
R2
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Received: 8th September 2015; Com. 15/4726
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