Nickel boride-mediated cleavage of 1,3-dithiolanes: A convenient approach to reductive desulfurization

Article abstract of DOI:10.1080/00397910903340652

1,3-Dithiolanes are rapidly cleaved by nickel boride, generating corresponding hydrocarbons in excellent yields. The hydrogenolysis is rapid at room temperature and does not require protection from the atmosphere. Mild reaction conditions, simple workup, and good yields of pure products are some of the major advantages of the procedure.

Full text of DOI:10.1080/00397910903340652

This article was downloaded by: [Boston University]
On: 29 October 2013, At: 01:30
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Nickel Boride–Mediated Cleavage of 1,3-
Dithiolanes: A Convenient Approach to
Reductive Desulfurization
Jitender M. Khurana a & Devanshi Magoo a
a Department of Chemistry , University of Delhi , Delhi, India
Published online: 25 Aug 2010.
To cite this article: Jitender M. Khurana & Devanshi Magoo (2010) Nickel Boride–Mediated Cleavage
of 1,3-Dithiolanes: A Convenient Approach to Reductive Desulfurization, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 40:19, 2908-2913,
DOI: 10.1080/00397910903340652
To link to this article: http://dx.doi.org/10.1080/00397910903340652
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Synthetic Communications1, 40: 2908–2913, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903340652
NICKEL BORIDE–MEDIATED CLEAVAGE OF
1,3-DITHIOLANES: A CONVENIENT APPROACH TO
REDUCTIVE DESULFURIZATION
Jitender M. Khurana and Devanshi Magoo
Department of Chemistry, University of Delhi, Delhi, India
1,3-Dithiolanes are rapidly cleaved by nickel boride, generating corresponding hydrocar-
bons in excellent yields. The hydrogenolysis is rapid at room temperature and does not
require protection from the atmosphere. Mild reaction conditions, simple workup, and good
yields of pure products are some of the major advantages of the procedure.
Keywords: Desulfurization; 1,3-dithiolanes; nickel boride; reduction; S,S acetals=ketals
INTRODUCTION
Desulfurization of organic compounds is essentially involved in the course of
chemical manipulation of polyfunctional molecules wherein the sulfur functionalities
must usually be removed in the final step. Also, there is a stringent requirement for
greener fuels with low sulfur content and therefore hydrogenolytic desulfurization
has wide applications in research on organic sulfur derivatives. These facts thus high-
light the need of newer methodologies that can efficiently reduce CÀS bonds to CÀH
bonds. Organosulfur compounds such as S,S acetals and ketals hold special
relevance because they have wide synthetic utility as carbonyl protecting groups as
a result of their remarkable stability under usual acidic or basic conditions[1] as well
as act as nucleophilic equivalents for CÀC bond formation[2] and enjoy a position of
prominence in designing strategies for construction of complex natural products.[3]
There are a plethora of methods available for deprotection of 1,3-dithiolanes to
corresponding aldehydes=ketones.[1] However, fewer methods are known for
reductive conversion of the 1,3-dithiolanes to the corresponding hydrocarbons of
parent carbonyl compounds. The most commonly used protocols employ Raney
nickel[4] or alkali metals in ammonia solution.[5] Reagents such as hydrazine[6] and
nickel complex reducing agents (NiCRA)[7] have also been used. Each of these meth-
ods has its own specific applications and at least one of the following drawbacks: dras-
tic conditions, tedious workup, long reaction times, poor yields, and use of expensive
reagents. Moreover, reagents such as sodium cyanoborohydride have been observed
to result in a mixture of saturated and unsaturated products in desulfurization
Received June 6, 2009.
Address correspondence to Jitender M. Khurana, Department of Chemistry, University of Delhi,
Delhi 110007, India. E-mail: jmkhurana1@yahoo.co.in
2908

DESULFURIZATION OF DITHIOLANES WITH NICKEL BORIDE
2909
reactions.[8] Further, the sulfur atoms of such heterocycles have a strong directing
effect toward metalations, alkylations, and other reactions, and therefore an improved
alternative procedure for this important transformation is of practical importance.
Nickel boride can be readily generated in situ from nickel(II) chloride and sodium
borohydride in protic conditions and has been employed as a reagent in a number
of important processes.[9] Reductive desulfurization of the C S group flanked by
=
ÀNHÀ has been successfully reported by our research group using nickel boride.[10]
As a part of our ongoing efforts to explore the various ambits where nickel boride can
prove to be an efficient reagent, we have investigated its role in the reductive desulfur-
ization of 1,3-dithiolanes.
RESULTS AND DISCUSSION
In this article, we report a simple and inexpensive procedure for reductive
desulfurization of 1,3-dithiolanes to hydrocarbons of parent carbonyl compounds
at ambient temperatures. 2,2-Diphenyl-[1,3]-dithiolane (Ia) was chosen as the model
substrate to investigate appropriate conditions for reductive desulfurization of
dithiolanes. As the activity of nickel boride is known to depend on the method of
its preparation, metal salt, and solvents,[9d] parameters had to be set by carrying
out the reactions of Ia with nickel boride in different solvents, and the reactions were
examined for optimum molar ratios of substrate to nickel boride. The solvents tetra-
hydrofuran (THF), acetonitrile, and dimethylformamide (DMF) resulted in sluggish
and incomplete reactions with a mixture of products, whereas no reaction was
observed in dichloromethane (DCM). No hydrogenolysis of dithiolanes was
observed when nickel(II) chloride and sodium borohydride were taken in equal
molar ratio. Only when their molar ratio was changed to 1:3 could we observe the
consumption of Ia to yield the corresponding hydrogenolyzed product. The reaction
of Ia with nickel(II) chloride and sodium borohydride in 1:3:9 molar ratio in
methanol=THF (4:1) was incomplete even after 24 h, although diphenylmethane
was formed. On increasing the molar ratio to 1:5:15, the reaction went to completion
in 20 min, yielding diphenylmethane (92%) exclusively with no side products.
Furthermore, it could be concluded undoubtedly that desulfurization was
proceeding as a result of the in situ formation of nickel boride because no reaction
of Ia was observed with nickel(II) chloride or sodium borohydride independently.
To check the generality of the transformation, reactions of a variety of S,S
ketals (alkyl aryl, diaryl) and S,S acetals were performed with nickel boride
(Scheme 1). A summary of the observations is presented in Table 1. The S,S ketal
of 9-flourenone could be desulfurized most easily to yield 94% fluorene in a 1:3:9
molar ratio. Further, entries 1–5 in Table 1 suggest that the substrates wherein the
umpolung site of the dithiolane ring (i.e., the initial carbonyl carbon), when flanked
by two aryl rings, require lower molar ratios of substrate to nickel boride as compared
to 2-phenyl-1,3-dithiolanes. The reaction of 2-styryl-[1,3]-dithiolane resulted in con-
comitant reduction of the double bond to yield n-propyl benzene (88%) (entry 18).
Thus, we conclude that nickel boride is an efficient, easily prepared, cheap, and
convenient reagent for the reductive desulfurization of 1,3-dithiolanes under non-
acidic, mild, and protic conditions at ambient temperature giving hydrocarbons in
excellent yields. This method circumvents the severity posed by older existing methods.

2910
J. M. KHURANA AND D. MAGOO
Table 1. Reduction of 1,3-dithiolanes using nickel boride in MeOH=THF (4:1) at room temperature
Substrate
(Ia–t)
Molar ratio
S=NiCl2 Á 6H2O=NaBH4
Time
(min)
Yield (%)
R1CH2R2 (Ia–t)
Entry
1
1:5:15
1:3:9
20
15
20
92
94
88
2
3
1:5:15
4
5
1:5:15
1:5:15
25
25
86
87
6
7
1:5:15
25
20
92
85
1:10:30
8
9
1:10:30
1:10:30
1:10:30
20
25
20
88
87
86
10
11
12
1:10:30
1:10:30
25
30
89
82
13
14
15
1:10:30
1:10:30
1:10:30
30
35
30
75
78
78
(Continued )

DESULFURIZATION OF DITHIOLANES WITH NICKEL BORIDE
2911
Table 1. Continued
Substrate
(Ia–t)
Molar ratio
S=NiCl2 Á 6H2O=NaBH4
Time
(min)
Yield (%)
R1CH2R2 (Ia–t)
Entry
16
1:10:30
1:10:30
30
30
80
82
17
18
1:10:30
35
88a
19
20
1:10:30
1:10:30
30
25
83
86
aThe isolated product was identified as n-propyl benzene.
Scheme 1. Reductive sulfurization of 1,3-dithiolanes with nickel boride.
EXPERIMENTAL
All products are known compounds. Melting points were recorded on a
Tropical Labequip apparatus and are uncorrected. The PMR spectra were recorded
on Hitachi FT-NMR (60 MHz) using tetramethylsilane (TMS) as internal standard.
The products were identified by melting point and superimposable IR and NMR
spectra with authentic samples. Methanol (S.D. Fine), nickel chloride hexahydrate
(S.D. Fine), and sodium borohydride (E. Merck) were used in all reactions.
General Procedure
In a typical reaction, a 50-mL, round-bottomed flask fitted with a reflux con-
denser was mounted over a magnetic stirrer, and 2,2-diphenyl-[1,3]-dithiolane (Ia)
(0.2 g, 0.77 mmol) dissolved in 10 mL methanol and THF (8:2) was placed in it.
NiCl2 Á 6H2O (0.92 g, 3.87 mmol) was added, followed (cautiously) by NaBH4
(0.44 g, 11.62 mmol). The reaction mixture was stirred vigorously at room tempera-
ture. The progress of the reaction was monitored by thin-layer chromatography

2912
J. M. KHURANA AND D. MAGOO
(TLC; petroleum ether=ethyl acetate 95:5). TLC showed complete disappearance of
the starting material after 20 min. The reaction mixture was filtered through a celite
pad (ꢀ2.5 cm) and washed with methanol (2 Â 10 mL). Water was added to the
filtrate, which was extracted with ethyl acetate (3 Â 10 mL). The combined extract
was dried over anhydrous MgSO4, decanted through a cotton pad, and concentrated
on a rotary evaporator to yield 0.12 g (92%) of diphenylmethane as characterized by
1
superimposable IR spectra and H NMR spectra.
ACKNOWLEDGMENTS
Financial assistance for the project by the University Grants Commission
[Project No. F-32-203=2006 (SR)] and a junior research fellowship to D. M. by
the Council of Scientific and Industrial Research are gratefully acknowledged.
REFERENCES
1. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd ed.; John
Wiley & Sons: New York, 1999; (b) Kocienski, P. J. Protecting Groups; George Thieme:
Sttugart, 1994.
2. (a) Seebach, D.; Corey, E. J. Generation and synthetic applications of 2-lithio-1,3-
dithianes. J. Org. Chem. 1975, 40, 231–237.
3. (a) Smith III, A. B.; Adams, C. M. Evolution of dithiane-based strategies for the construc-
tion of architecturally complex natural products. Acc. Chem. Res. 2004, 37, 365–377; (b)
´
Yus, M.; Najera, C.; Fourbelo, F. The role of 1,3-dithianes in natural product synthesis.
Tetrahedron 2003, 59, 6147–6212.
4. Hauptman, H.; Walter, W. F. The action of Raney nickel on organic sulfur compounds.
Chem. Rev. 1962, 62, 347.
5. (a) Ireland, R. E.; Wrigley, T. I.; Young, W. G. Allylic rearrangements, XLI: The reaction
of thionyl chloride with steroid allylic alcohols. J. Am. Chem. Soc. 1958, 80, 4604; (b)
Crossley, N. S.; Henbest, H. B. Syntheses of perhydroanthracenes involving the reduction
of thioketals with lithium and ethylamine: The synthesis of 1,4,4-a,a-5,8,8-a,b-9,9-a,b-
10,10-a,a-decahydroanthracene. J. Chem. Soc. 1960, 4413.
6. Corey, E. J.; Ohno, M.; Mitra, R. B.; Vatakencherry, P. A. Total synthesis of longifolene.
J. Am. Chem. Soc. 1964, 86, 478.
`
7. Becker, S.; Fort, Y.; Caubere, P. New desulfurizations by nickel-containing complex
reducing agents. J. Org. Chem. 1990, 55, 6194.
8. Okazaki, R.; Unno, M.; Inamoto, N. A new synthesis of 1,3-thiazine derivatives having a
dithiolane ring and their reductive cleavage with sodium cyanoborohydride. Heterocycles
1987, 25, 183.
9. (a) Schlesinger, H. I.; Brown, H. C.; Finholt, A. E.; Galbreath, J. R.; Hoeckstra, H. R.;
Hyde, E. K. Sodium borohydride, its hydrolysis, and its use as a reducing agent and in
the generation of hydrogen. J. Am. Chem. Soc. 1953, 75, 215; (b) Schlesinger, H. I.;
Brown, H. C. Preparation of alkali metal compounds. U.S. Patent 2,461,661, 1949; (c)
Ganem, B.; Osby, J. O. Synthetically useful reactions with metal boride and aluminide
catalysts. Chem. Rev. 1986, 86, 763; (d) Khurana, J. M.; Gogia, A. Synthetically useful
reactions with nickel boride: A review. Org. Prep. Proc. Int. 1997, 29, 1.
10. (a) Khurana, J. M.; Kukreja, G.; Bansal, G. Desulfurization of thioureas, benzimidazoline-
2-thiones, and 1,3-dihydro-1,3-diaryl-2-thioxopyrimidine-4,6(2H,5H)-diones with nickel
boride at ambient temperature. J. Chem. Soc., Perkin Trans. 1, 2002, 2520; (b) Khurana,

DESULFURIZATION OF DITHIOLANES WITH NICKEL BORIDE
2913
J. M.; Kukreja, G. Nickel boride–mediated reductive desulfurization of 2-thioxo-4(3H)-
quinazolinones: new synthesis of quinazolin-4(3H)-ones and 2,3-dihydro-4(1H)-
A
quinazolinones. J. Heterocycl. Chem. 2003, 40, 677; (c) Khurana, J. M.; Agrawal, A.;
Kukreja, G. A novel two-step synthesis of 3,4-dihydro-4-oxo-5H-pyrano[2,3-d]pyrimidines.
Heterocycles 2006, 68, 1885; (d) Khurana, J. M.; Arora, R.; Satija, S. 7,11-Diaryl-2,4-
diazaspiro[5.5]undecane-1,5,9-triones: A new series of spiroheterocycles. Heterocycles
2007, 71, 2709; (e) Khurana, J. M.; Sharma, V. A novel synthesis of 2-substituted 2H-imi-
dazo[1,5-b]isoquinoline-1,5-diones by in situ desulfurization. Chem. Heterocycl. Compd.
2008, 44, 309; (f) Khurana, J. M.; Kumar, S.; Nand, B. Facile reductive dehalogenation
of organic halides with nickel boride at ambient temperature. Can J. Chem. 2008, 86, 1052.