Phenylsilane as an effective desulfinylation reagent

Article abstract of DOI:10.3762/bjoc.13.150

The reduction using phenylsilane in a KOH-catalyzed system was applied successfully to the conversion of sulfinyl-substituted cyclopropylcarboxylates into the corresponding alcohols. The presence of sulfinyl substituents in the α-position to the carboxylate group caused a desulfinylation product formation with full regio- and stereoselectivity, instead of a carbonyl group reduction. Investigations performed on different α-sulfinylcarbonyl compounds revealed that phenylsilane treatment constitutes a regiospecific method for the desulfinylation of a-sulfinylesters; for corresponding ketones the reaction course depends on the character of the carbonyl group.

Full text of DOI:10.3762/bjoc.13.150

Phenylsilane as an effective desulfinylation reagent
Wanda H. Midura*, Aneta Rzewnicka and Jerzy A. Krysiak
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2017, 13, 1513–1517.
Centre of Molecular and Macromolecular Studies, Polish Academy of
Sciences, Department of Heteroorganic Chemistry, Sienkiewicza 112,
90-363 Łódź, Poland
doi:10.3762/bjoc.13.150
Received: 01 May 2017
Accepted: 20 July 2017
Published: 01 August 2017
Email:
Wanda H. Midura* - whmidura@cbmm.lodz.pl
Associate Editor: T. P. Yoon
* Corresponding author
© 2017 Midura et al.; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
desulfinylation; phenylsilane; reduction; regioselectivity;
α-sulfinylesters
Abstract
The reduction using phenylsilane in a KOH-catalyzed system was applied successfully to the conversion of sulfinyl-substituted
cyclopropylcarboxylates into the corresponding alcohols. The presence of sulfinyl substituents in the α-position to the carboxylate
group caused a desulfinylation product formation with full regio- and stereoselectivity, instead of a carbonyl group reduction. In-
vestigations performed on different α-sulfinylcarbonyl compounds revealed that phenylsilane treatment constitutes a regiospecific
method for the desulfinylation of a-sulfinylesters; for corresponding ketones the reaction course depends on the character of the car-
bonyl group.
Introduction
The conversion of carboxylic acid derivatives to the corre- known metal-catalyzed hydrosilylation, transition metals in the
sponding alcohols is one of the fundamental processes in presence of Brønsted or Lewis acids were used for the reduc-
organic synthesis. Over the past decades, many reagents and tion. Recently base-activated silanes were also used for this
conditions for this transformation have been reported. Apart purpose [15-17].
from traditional hydride reducing agents like lithium aluminum
hydride and sodium borohydride [1,2], different modifications Results and Discussion
were applied, using transition metal salts as catalysts or addi- Our recent investigations were connected with the synthesis and
tives to change or enhance the properties of these reagents further conversion of multifunctional cyclopropanes, where the
[3-8]. Hydrogenation is another convenient method for the carboxylate moiety was present in close proximity to sulfinyl
reduction of carbonyl compounds, although low selectivities and phosphoryl substituents [18-20]. A selective and effective
have sometimes been observed and the reaction usually re- method of the independent conversion of each of these substitu-
quired drastic conditions [9]. Also, the catalytic hydrosilylation ents is therefore a subject of our interest. To extend the investi-
of carbonyl moieties has become an important transformation as gations on the reduction of esters using a reagent with tolerance
an alternative reduction methodology [10-14]. Besides the well- for other functional groups present in the structure, we applied a
1513

Beilstein J. Org. Chem. 2017, 13, 1513–1517.
hydrosilylation methodology (Scheme 1). Various cyclopropyl Cyclopropane 4 was formed by carboxylation of 3 with ethyl
phosphonates were subjected to the reaction with an excess of chloroformate as a continuation of our studies on asymmetric
phenylsilane under neat reaction conditions in the presence of a cyclopropanation of vinyl phosphonates using (S)-dimethylsul-
catalytic amount of KOH. It appeared that results of this reac- fonium(p-tolylsulfinyl)methylide and its further application. It
tion strongly depended on the relative position of particular sub- was formed as a single diastereomer with full stereoselectivity.
stituents [21].
To determine the relative configuration of the obtained struc-
ture, in the absence of an α-proton at the sulfinyl group which
For compounds 1 and 2 the treatment with phenylsilane caused, was conclusive in our former studies, we benefited from
as expected, in a reduction of the ester group. In both cyclo- 13C NMR analysis. The small value of coupling constant
propanes the carboxylate moiety and the sulfinyl group were in 3JP-C = 4 Hz indicated a trans relationship between the carbox-
vicinal relation, but in 1, formed in the reaction of vinyl phos- ylate and the phosphoryl substituent.
phoryl sulfoxide with EDSA [22], the ester group was easily
accessed, since the bulky phosphoryl group was also in vicinal Desulfinylation of cyclopropane 4 under conditions used by us
position to the sulfoxide substituent. Compounds 2 and 3 were before, i.e., by treatment with isopropylmagnesium chloride,
obtained by us earlier [23] in diastereomerically pure form as gave a mixture of diastereomers 7a and 7b. It was probably due
key intermediates in our approach to constrained phosphonic to epimerization on carbon C2 of the carbanion, formed after
acids by the reaction of phosphoryl acrylates with (S)-dimethyl- attack of the Grignard reagent on sulfur. To our satisfaction,
sulfonium(p-tolylsulfinyl)methylide. The carboxylate moiety utilization of the silane procedure led to the single diastereomer
was geminal to the phosphoryl substituent in these compounds. 7a. In this case determination of the relative configuration as
In the case of cyclopropane 3 the reduction did not occur, since trans was based on a high coupling constant 3JP-H = 17.0 Hz,
the bulky tert-butyl substituent effectively protected the carbox- which evidenced retention of configuration during the
ylate group. Hence, the starting material was recovered.
desulfinylation process (Scheme 2).
The next cyclopropane 4, which contained the sulfinyl substitu- The reaction conducted under solvent-free conditions with a
ent in geminal position to the ester group, was subjected to a large excess of silyl reagent (procedure 1) occurred with full
reaction with phenylsilane using the procedure described above. conversion of the cyclopropanes, although some problems with
In this case, to our surprise, no alcohol was detected, but the the isolation of the product due to an excess of silane induced a
desulfinylation process occurred exclusively.
modification of the reduction procedure. The gain of using THF
Scheme 1: Different behaviour of cyclopropylphosphonates in the reaction with phenylsilane.
1514

Beilstein J. Org. Chem. 2017, 13, 1513–1517.
Scheme 2: Synthesis and desulfinylation of 4.
as a solvent [17] (procedure 2) let us decrease the amount of stituents in geminal position. This relation turned out to be more
phenylsilane used in the reaction medium, which resulted in a complex and was depended on the ketone structure (Table 1).
high yield of the corresponding cyclopropane 7a.
Introduction of an acyl moiety by substitution of 3 with acetic
The obtained results demonstrated that the presence of a anhydride led to compound 12, which was subjected to the reac-
sulfinyl substituent in α position to the carboxylate completely tion with PhSiH3/KOH. Also in this case desulfinylation of
changed the direction of the silane attack on the structure, so cyclopropane took place leading to 13 as a major product, how-
this reaction could be considered as a new regiospecific method ever, accompanied by the corresponding alcohol 14, formed as
of a desulfinylation. In order to examine the scope of observed a result of the subsequent reduction of the carbonyl group
desulfinylation different carbonyl compounds with sulfinyl (Table 1, entries 1 and 2). Oxidation of the crude mixture by
substituents were synthetized and subjected to the reaction stirring with chromium trioxide and pyridine allowed to obtain
with phenylsilane. Reactions of α-sulfinylcarboxylates 9 desulfinylated ketone 13 in a reasonable yield.
and 10 with phenylsilane evidenced that the desulfinylation
process occurred also in the case of acyclic sulfoxides For acyclic structures the reaction course dramatically depended
(Scheme 3).
on the character of ketone. In the case of aliphatic ketone 15,
silane treatment gave desulfinylated product 17 as the only
α-Sulfinylphenylacetate 9 was formed as a mixture of diastereo- product (Table 1, entry 3). However, the presence of a more
mers difficult to separate. This mixture, without separation, was electrophilic aryl ketone group in 19 caused that the reduction
subjected to the reaction with phenylsilane utilizing the proce- of carbonyl group took place, leading to alcohol 21 without
dure described above and afforded phenylacetate 8 as the only desulfinylation (Table 1, entry 5).
product. Methylation of 9 afforded product 10 with full stereo-
selectivity as the only diastereomer although the configuration For comparison, for analogous carbonyl structures with sulfide
of this center was not determined. Also in this case treatment substituents, under these conditions, reduction of the carbonyl
with PhSiH3/KOH caused a desulfinylation process leading to group occurred leading to the corresponding alcohols (18 [25],
ester 11 [24]. Unfortunately in this case the stereogenic center 22) as the only products in high yield. It means that attack on
at the carbon undergoes epimerization under these reaction sulfur is not connected with the presence of a C–S bond but a
conditions and 11 is obtained in racemic form.
sulfinyl substituent is required.
To study the scope and limitation of the silane reactivity and its In a former research performed by Fernandes and Romão [26],
selectivity we checked the influence of the ketone function on an α-sulfinyl-substituted ester (methyl(phenylsulfinyl)acetate)
the behaviour of the compounds with sulfur and carbonyl sub- was treated by phenylsilane, but using a silane/MoO2Cl2 system
Scheme 3: Reaction of acyclic sulfoxides with phenylsilane. Reagents and conditions: (a) BuLi, THF, −70 °C, p-TolS(O)Men; (b) PhSiH3, THF, rt,
KOH (5 mol %); (c) MeI, 50% KOH, CH2Cl2.
1515

Beilstein J. Org. Chem. 2017, 13, 1513–1517.
Table 1: Reaction of compounds with sulfur and carbonyl substituents in geminal relation with PhSiH3/KOH.
Entry
Ketone
12
Reaction conditions
Product of reduction
Product of desulfinylation
1
2
3
4
5
6
5 equiv PhSiH3, 0.1 equiv KOH,
0.5 h, rt, 20% conv.
not detected
13/14
2:1
12
5 equiv PhSiH3, 0.1 equiv KOH,
5 h, rt, 100% conv.
not detected
13/14
2:1
15
5 equiv PhSiH3, 0.1 equiv KOH,
5 h, rt, 100% conv.
not detected
17
16
5 equiv PhSiH3, 0.1 equiv KOH,
5 h, rt, 100% conv.
12
21
22
not detected
not detected
not detected
19
5 equiv PhSiH3, 0.1 equiv KOH,
5 h, rt, 100% conv.
20
5 equiv PhSiH3, 0.1 equiv KOH,
5 h, rt, 100% conv.
as a catalyst. Under those conditions both functional groups pounds of this type by phenylsilane was observed for the first
were reduced, leading to the corresponding α-phenylsulfenyl time, so far unknown in the literature. This approach increases
alcohol. The desulfinylation process of compounds of this type the number of selective desulfinylation methods which can be
by phenylsilane is the first observation. It is unknown until now performed under mild conditions [31-33]. The reactivity of
in literature. One could assume that the active species, usually α-sulfinylketones with phenylsilane is less regioselective and
postulated in the fluoride- and base-catalyzed hydrosilylation the direction of the reaction strongly depends on the character
[27-30], in the presented case is additionally chelated by both of the ketone.
polar carbonyl substituents. It facilitates hydride anion forma-
tion, which attacks the most electrophilic center of a particular
Supporting Information
structure.
Supporting Information File 1
Experimental and analytical data and NMR spectra.
Conclusion
A phenylsilane/KOH system was successfully applied as a
reducing agent for conversion of different cyclopropylcarboxy-
lates to the corresponding alcohols. However, our study
revealed that the presence of a sulfinyl substituent in the
α-position to the carboxylate moiety totally changes the direc-
tion of the reaction, leading to the corresponding ester deprived
of the sulfinyl group. The desulfinylation process of com-
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-13-150-S1.pdf]
Acknowledgements
This research was supported by the National Science Grant No
DEC-2013/11/B/ST5/01589.
1516

Beilstein J. Org. Chem. 2017, 13, 1513–1517.
27.Lawrence, N. J.; Drew, M. D.; Bushell, S. M.
References
J. Chem. Soc., Perkin Trans. 1 1999, 3381–3391.
doi:10.1039/a903662h
1. Seyden-Penne, J. Reductions by the Alumino- and Borohydrides in
Organic Synthesis, 2nd ed.; Wiley: New York, 1997.
2. Gribble, G. W. Chem. Soc. Rev. 1998, 27, 395–404.
doi:10.1039/a827395z
28.Kobayashi, Y.; Takahisa, E.; Nakano, M.; Watatani, K. Tetrahedron
1997, 53, 1627–1634. doi:10.1016/S0040-4020(96)01092-7
29.Hojo, M.; Murakami, C.; Fujii, A.; Hosomi, A. Tetrahedron Lett. 1999,
40, 911–914. doi:10.1016/S0040-4039(98)02480-0
30.Hojo, M.; Fujii, A.; Murakami, C.; Aihara, H.; Hosomi, A. M.
Tetrahedron Lett. 1995, 36, 571–574.
3. Ganem, B.; Osby, J. O. Chem. Rev. 1988, 86, 763–780.
doi:10.1021/cr00075a003
4. Kanth, J. V. B.; Periasamy, M. J. Org. Chem. 1991, 56, 5964–5965.
doi:10.1021/jo00020a052
doi:10.1016/0040-4039(94)02255-A
5. Narasimhan, S.; Madhavan, S.; Prasad, K. G. J. Org. Chem. 1995, 60,
5314–5315. doi:10.1021/jo00121a060
31.Capozzi, M. A. M.; Cardellicchio, C.; Naso, F.; Tortorella, P.
J. Org. Chem. 2000, 65, 2843–2846. doi:10.1021/jo991912q
32.García Ruano, J. L.; Marzo, L.; Marcos, V.; Alvarado, C.; Alemán, J.
Chem. – Eur. J. 2012, 18, 9775–9779. doi:10.1002/chem.201201607
33.Frutos, M.; Ortuño, M. A.; Lledos, A.; Viso, A.;
6. Reding, M. T.; Buchwald, S. L. J. Org. Chem. 1995, 60, 7884–7890.
doi:10.1021/jo00129a031
7. Jagdale, A. R.; Paraskar, A. S.; Sudalai, A. Synthesis 2009, 660–664.
doi:10.1055/s-0028-1083353
Fernández de la Pradilla, R.; de la Torre, M. C.; Sierra, M. A.;
Gornitzka, H.; Hemmert, C. Org. Lett. 2017, 19, 822–825.
doi:10.1021/acs.orglett.6b03808
8. Morales-Serna, J. A.; García-Rios, E.; Bernal, J.; Paleo, E.; Gaviño, R.;
Cárdenas, J. Synthesis 2011, 1375–1382.
doi:10.1055/s-0030-1259988
9. Pouilloux, Y.; Autin, F.; Barrault, J. Catal. Today 2000, 63, 87–100.
doi:10.1016/S0920-5861(00)00448-X
10.Marciniec, B.; Maciejewski, H.; Pietraszuk, C.; Pawluć, P.
Hydrosilylation. In A Comprehensive Review on Recent Advances;
Marciniec, B., Ed.; Springer, 2009; pp 290–326.
License and Terms
This is an Open Access article under the terms of the
Creative Commons Attribution License
11.Marciniec, B. Coord. Chem. Rev. 2005, 249, 2374–2390.
doi:10.1016/j.ccr.2005.02.025
12.Addis, D.; Das, S.; Junge, K.; Beller, M. Angew. Chem., Int. Ed. 2011,
50, 6004–6011. doi:10.1002/anie.201100145
(http://creativecommons.org/licenses/by/4.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
13.Marciniec, B.; Gulinsky, J.; Urbaniak, W.; Kornetka, Z. W. In
Comprehensive Handbook on Hydrosilylation; Marciniec, B., Ed.;
Pergamon: Oxford, 1992.
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
14.Ojima, I. In The Chemistry of Organic Silicon Compounds; Patai, S.;
Rappoport, Z., Eds.; Wiley: Chichester, 1989; Vol. 1.
15.Fedorov, A.; Toutov, A. A.; Swisher, N. A.; Grubbs, R. H. Chem. Sci.
2013, 4, 1640–1645. doi:10.1039/c3sc22256j
(http://www.beilstein-journals.org/bjoc)
16.Fernández-Salas, J. A.; Manzini, S.; Nolan, S. P. Chem. Commun.
2013, 49, 9758–9760. doi:10.1039/c3cc45930f
The definitive version of this article is the electronic one
which can be found at:
17.Revunova, K.; Nikonov, G. I. Chem. – Eur. J. 2014, 20, 839–845.
doi:10.1002/chem.201302728
doi:10.3762/bjoc.13.150
18.Midura, W. H.; Cypryk, M.; Rzewnicka, A.; Krysiak, J. A.; Sieroń, L.
Eur. J. Org. Chem. 2016, 2064–2074. doi:10.1002/ejoc.201600111
19.Midura, W. H.; Krysiak, J.; Rzewnicka, A.; Supeł, A.; Łyżwa, P.;
Ewas, A. M. Tetrahedron 2013, 69, 730–737.
doi:10.1016/j.tet.2012.10.085
20.Krysiak, J.; Midura, W. H.; Wieczorek, W.; Sieroń, L.; Mikołajczyk, M.
Tetrahedron: Asymmetry 2010, 21, 1486–1493.
doi:10.1016/j.tetasy.2010.04.051
21.Midura, W. H.; Rzewnicka, A.; Krysiak, J. A.
Phosphorus, Sulfur Silicon Relat. Elem. 2017, 192, 180–181.
doi:10.1080/10426507.2016.1250763
Preliminary results of this work were presented ISOCS-27, Jena, 2016.
22.Midura, W. H.; Krysiak, J.; Mikołajczyk, M. Tetrahedron: Asymmetry
2003, 14, 1245–1249. doi:10.1016/S0957-4166(03)00211-8
23.Midura, W. H.; Rzewnicka, A. Tetrahedron: Asymmetry 2013, 24,
937–941. doi:10.1016/j.tetasy.2013.05.024
24.Yamashita, T.; Yasueda, H.; Miyauchi, Y.; Nakamura, N.
Bull. Chem. Soc. Jpn. 1977, 50, 1532–1534. doi:10.1246/bcsj.50.1532
25.Sun, J.; Yang, M.; Yuan, F.; Jia, X.; Pan, Y.; Zhu, C. Adv. Synth. Catal.
2009, 351, 920–930. doi:10.1002/adsc.200800767
26.Fernandes, A. C.; Romão, C. C. J. Mol. Catal. A: Chem. 2006, 253,
96–98. doi:10.1016/j.molcata.2006.03.006
1517