Woollins’ reagent promotes selective reduction of α,β-unsaturated thiazo and selenazolidinones

Article abstract of DOI:10.1016/j.tetlet.2017.02.053

In this work we describe the Woollins’ reagent as useful for the selective reduction of the double bond of 2-α,β-unsaturated thiazo and selenazolidinones. The reaction took place in toluene at room temperature to give the corresponding saturated heterocyc

Full text of DOI:10.1016/j.tetlet.2017.02.053

Accepted Manuscript
Woollins’ Reagent promotes selective reduction of α,β-unsaturated thiazo and
selenazolidinones
Chiara Pizzo, Graciela Mahler
PII:
S0040-4039(17)30228-9
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.02.053
TETL 48664
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Accepted Date:
30 January 2017
15 February 2017
Please cite this article as: Pizzo, C., Mahler, G., Woollins’ Reagent promotes selective reduction of α,β-unsaturated
thiazo and selenazolidinones, Tetrahedron Letters (2017), doi: http://dx.doi.org/10.1016/j.tetlet.2017.02.053
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Leave this area blank for abstract info.
Woollins’ Reagent promotes selective
reduction of α,β-unsaturated thiazo and
selenoazolidinones
Chiara Pizzo and Graciela Mahler

1
Tetrahedron Letters
journal homepage: www.els evier.com
Woollins’ Reagent promotes selective reduction of α,β−unsaturated
thiazo and selenazolidinones
Chiara Pizzo a and Graciela Mahlera, ∗
a
Departamento de Química Orgánica, Laboratorio de Química Farmacéutica, Universidad de la República (UdelaR), Avda. General Flores 2124, CC1157,
Montevideo, Uruguay
ARTICLE INFO
ABSTRACT
Article history:
Received
In this work we describe the Woollins’ reagent as useful for the selective reduction of the double
bond of 2-α,β-unsaturated thiazo and selenazolidinones. The reaction took place in toluene at
room temperature to give the corresponding saturated heterocycles in good yields, eleven
examples are given. The scope of the reaction is also discussed, been esential the conjugated
ester to the double bond.
Received in revised form
Accepted
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Woollin's reagent
Selenazolidinones
Thiazolidinones
Selective reduction of α,β-unsaturated esters
———
∗ Corresponding author. Tel.: +-598-200-0000; fax: +0-000-000-0000; e-mail: gmahler@fq.edu.uy

2
Tetrahedron Letters
1. Introduction
As part of our interest in the preparation and biological
evaluation of organoselenium compounds,10,11 we worked on a
general approach towards the synthesis of selenazolyl
compounds. Based on the known uses of WR, we decided to
explore its utility for the preparation of thiazolidin-selenones.
Woollins' reagent (WR) is the 2,4-Bis(phenyl)-1,3-
diselenadiphosphetane-2,4-diselenide and it plays an essential
role in the selenation of organic compounds, see Figure 1.1 It is
described that reacts with secondary and tertiary amides to obtain
selenoamides by simple oxygen-selenium exchange.2 The
reaction
of
arylnitriles
with
WR/H2O
produces
arylselenoamides.3 It has also been used for the synthesis of
selenadiazoles,4 and P−Se heterocycles.5 Another application is
the C-C bond formation for the reductive coupling reaction of
aldehydes and ketones,6 see Figure 1.
Se
R2
N
R1
R
R2
R
R
N
R1
O
R1
R1
1
R
Scheme 1. Selective reduction of the α,β-unsaturated
thiazolidinone 1a, and synthesis of selenoamide 4a, using WR
ref 6
ref 2
Se
Ph
Se
Se
Se
H
R
P
R
H
P
RCHO
ref 6
R
C
N
Ph
H2N
R
Se
When thiazolidinone 1a was treated with WR in toluene at
room temperature, the reduced thiazolidin-4-one 2a was
obtained, instead of the expected thiazolidine-4-selenone, see
Scheme 1. When we tryed to obtain the desired seleno derivative
starting with the amide derivative 3a, a selective O-Se exchange
occurred at the exocyclic amide instead of the lactame ring,
giving thiazolidinone selenoamide 4a. Adding more equivalents
or increasing the reaction time did not led to the O-Se exchange
at the ring, see Scheme 1.
ref 3
WR
O
O
R1
Ar
H
HN
N
H
ref 5
ref 4
R
Ph
Se
Se
N
N
P
Se
Ar
Se
R1
R
Figure 1. Synthetic applications of Woollins’Reagent (WR).
In order to gain insight into the reduction reaction, we decided
to further explore the utility of WR as a selective reducing agent
The advantages of using WR as selenating agent relies on its
better stability on air, compared with H2Se, and that it is either
commercially available or easily prepared from PhPCl2 and
Na2Se.5
for
α,β-unsaturated heterocycles.
For this purpose,
thiazolidinones 1b-1j were treated with WR, using the same
conditions used for 1a, to obtain reduced compounds 2b-2j.
Thiazolidinones 1a-j were prepared according to a previous
one-pot methodology, by condensation of aromatic aldehydes or
ketones, thiosemicarbazide or methyl thiosemicarbazide and
methyl acetylenedicarboxylate.12 The reduced derivatives 2a-j
were smoothly obtained in toluene at room temperature using
WR (1 eq) with moderated to good yields (25 to 89%), see Table
1.
The interest in organoselenium compounds has been growing
during the last decades due to its importance as useful
intermediates in synthetic chemistry,7 and as new materials,8 but
the most outstanding field is related to its biological and
medicinal significance.9
Table 1. Selective olefin reduction in α,β-unsaturated thiazo and selenazolidinones, using WR
Entry
R1
Ph
R2
Me
Me
Me
H
R3
Me
H
X
Yield %a
2a, 55
2b, 72
2c, 77
2d, 68
2e, 79
2f, 74
2g, 58
2h, 25
2i, 89
1
S
2
m,p-diCl Ph
m-Br Ph
S
S
S
S
S
S
S
S
S
Se
3
H
4
p-Cl Ph
Me
Me
Me
H
5
p-CF3 Ph
H
6
p-OMe Ph
p-OMe Ph
m-Me Ph
H
7
H
8
H
H
9
o,m-OMe Ph
Thiophene
m,p-diCl Ph
H
H
10
11
H
H
2j, 50
2k, 67
Me
H
a Isolated yields.

3
Generally, N-methyl substituted thiazolidinones gave better
yields than the N-unsubstituted ones, as evidenced for
compounds 2f vs 2g (74 and 58% yield, respectively, see entries
6 and 7, Table 1). In this context, the reaction yields seem to be
favored when using thiazolidinones derived from aldehydes (R2 =
H), instead of those derived from ketones (R2 = Me), yields
ranging from 68 to 74%, see entries 4-6.
Electron donating or withdrawing groups (EDG and EWG
respectively) in the phenyl ring, did not affect the final yields. As
an example, strong EDG present in 2i displays the highest yield
(89%, see entry 9, Table 1), but the methyl derivative 2h, bearing
a medium EDG showed the lowest yield (25%, see entry 8, Table
1). A similar behavior is observed when using EWG.
To further evaluate the scope of WR as a reducing agent, we
prepared the α,β-unsaturated selenazolidinone 1k, and the
treatment with WR led to the reduced product 2k in 67% yield
(see entry 11, Table 1).
Scheme 3. Proposed mechanism for the selective reduction of
α,β-unsaturated thiazo and selenazolidinone compounds.
could explain the importance of the α,β-conjugated ester in the
selective reduction mechanism.
Benzylidenes 6a-b,13 were also selected as substrates; see
Scheme 2. The main difference in both substrates is the
α,β−conjugated group: a benzylidene (6) instead of an ester (2).
When we applied the protocol to 6a-b after 48 h at rt, or even at
reflux, the starting material was recovered and no reduced
product was formed, pointing out the needed of the ester as an
EWG to reduce the substrate.
A series of heterocycles α,β-unsaturated esters (1a-1k) were
selectively reduced to the corresponding saturated heterocycles
2a-2k, using WR and mild reaction conditions.
It seems that the reaction is not sensitive to the electronic
effects in the aromatic ring of the thiazolidinones. Therefore,
when using either electron-donating (-OMe, -Me) or electron-
withdrawing groups (-Br, -Cl), the desired reduction products
were obtained in good yields (Table 2, entries 1-10). Besides, the
position of the substituent groups did not considerably affect the
reactivity.
Looking for a plausible mechanism for the reduction we
explored in literature for antecedents. It is described the use of
NaSeH and LiSeH as selective reducing agents of α,β-
unsaturated carbonyl compounds.14 Recently, Alves and co-
workers reduced electron deficient olefins as chalcones using
PhSe-SePh.15 WR was also used as a chemoselective reductive
agent for diketones, reported by Jaisankar and co-workers.16
In this sense, a new applicability of Woollins’ reagent is
a selective reducing agent of thiazo or
described as
selenazolidinone olefins conjugated to esters.
Based on this background and our findings, we suggested a
possible mechanism for the selective reduction, as it is depicted
in Scheme 3.
Acknowledgments
It is reported that WR is in equilibrium with
a
diselenaphosphorane species, being the reactive one in solution.17
The conjugated addition of the Se atom to the α,β unsaturated
ester gives the intermediate I, that could undergo Se0 to form
compound 2 formation.
The CSIC-Grupos UdelaR supported this work. C.P. is
grateful to the Agencia Nacional de Investigación e Innovación
(ANII) for a fellowship (BE_POS_2010_1_2362). We thank Dr.
A. Rodríguez-Haralambides for HRMS.
References and notes
1. Woollins, J.D.; Hua, G. Angew. Chem. Int. Ed. 2009, 48, 1368.
2. Bhattacharyya, P.; Woollins, J.D. Tetr. Lett. 2001, 42, 5949.
3. Hua, G.; Li, Y.; Slawin, A.M.Z.; Woollins, J.D. Org. Lett., 2006,
8,5251
O
O
NH
NH
O
O
H
O
O
S
S
R
WR
PhMe, rt
NH
X
4. Ostrowski, W.; Gierczyk, B.; Frański, R. J .Heterocycl. Chem.
2012, 49, 1266.
O
S
PhMe, reflux
6a-b
7a-b
5
5. Gray, I.P; Bhattacharyya, P.; Slawin, A.M.Z.; Woollins, J.D.
Chem. Eur. J. 2005, 11, 6221.
6a: R = OMe, 95%
6b: R = CF3, 91%
R
R
6. Hua, G.; Li, Y.; Slawin, A.M.Z.; Woollins, J.D. Dalton Trans.
2007, 15, 1477.
Scheme 2. Synthesis of thiazolidinones 6a-b and its attempt
7. (a) Liotta, D.; Monahan, R. Science. 1986, 231, 356; (b) Wirth, T.
Angew. Chem. Int. Ed. 2000, 39, 3740; (c) Rhoden, C. R. B.; Zeni,
G. Org. Biomol. Chem. 2011, 9, 1301; (d) Levason, W.; Reid, G.;
Zhang, W. Dalton Trans. 2011, 40, 8491.
to reduction
According to the proposed mechanism for the selective α,β
reduction, a 1,4 Se attack of the diselenaphosphorane specie
would take place.
8. (a) Garían, J. Adv. Heterocycl. Chem. 1995, 62, 249; (b) Uemoto,
T. Adv. Heterocycl. Chem. 1995, 64, 323; (c) Swapna, K.; Murthy,
S. N.; Nageswar, Y. V. D. Eur. J. Org. Chem. 2011, 10, 1940.
9. (a) Mugesh, G.; du Mont, W. W.; Sies, H. Chem. Rev. 2001, 101,
2125; (b) Nogueira, C. W.; Zeni, G.; Rocha, T. B. T. Chem. Rev.
2004, 104, 6255; (c) Ninomiya, M.; Garud, D R.; Koketsu, M.
Coord. Chem. Rev. 2011, 255, 2968.
Comparing both electron withdrawing groups (ester
compounds 1a-k, and p-trifluoromethyl phenyl moiety,
compound 6b), it is noticeable that the conjugation obtained
using an α,β ester gets a more activated 4 position, for the attack
of the Se, according to the mechanistic proposal. These results
10. Pizzo, C.; Faral-Tello, P.; Salinas, G.; Fló, M.; Robello, C.; Wipf,
P.; Mahler, S. G. Med. Chem. Commun. 2012, 3, 362.
11. Pizzo, C.; Faral-Tello, P.; Robello, C.; Mahler, G. Eur. J. Med.
Chem. 2016, 109, 107.

4
Tetrahedron
12. Pizzo, C.; Saiz, C.; Talevi, A.; Gavernet, L.; Palestro, P.;
Supplementary Material
Bellera, C.; Blanch, L.B.; Benítez, D.; Cazzulo, J.J.; Chidichimo,
A.; Wipf, P.; Mahler, S.G. Chem. Biol. Drug. Des. 2011, 77, 166.
13. Castillo, V.; Fagúndez, C.; Martínez, V.; Peña, S.; Pizzo, C.; Saiz,
C.; Scarone, L.; Mahler, S.G. ALDEQ, 2012, 27,161.
14. Nishiyama, Y.; Yoshida, M.; Ohkawa, S.; Hamanaka, S. J. Org.
Chem. 1991, 56, 6720.
Supplementary material that may be helpful in the review
process should be prepared and provided as a separate electronic
file. That file can then be transformed into PDF format and
submitted along with the manuscript and graphic files to the
appropriate editorial office.
15. Mesquita, K.D.; Waskow, B.; Schumacher, R.F.; Perin, G.; Jacob,
R.G.; Alves, D. J. Braz. Chem. Soc. 2014, 25, 1261.
16. Mandal, M.; Chatterjee, S.; Jaisankar, P. Synlett 2012, 23, 2615.
17. Hua, G.; Li, Y.; Slawin, A.M.Z.; Woollins, J.D. Eur. J. Inorg.
Chem. 2007, 6, 891.
Click here to remove instruction text...

-
-
-
A new synthetic applicability of Woollins’ reagent (WR) is described.
WR was a selective reducing agent of thiazo or selenoazolidinone olefins.
The scope of the reaction was investigated, been essential the conjugation of the
double bond with an ester group
-
-
The yields were ranged from 25 to 89 %
A plausible mechanism for the reduction was proposed