Deiodination of iodolactones by transfer hydrogenolysis using Raney nickel and 2-propanol

Article abstract of DOI:10.1081/SCC-120004856

Raney nickel in refluxing 2-propanol is an effective catalytic system for reducing iodolactones into their corresponding lactones.

Full text of DOI:10.1081/SCC-120004856

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DEIODINATION OF IODOLACTONES BY TRANSFER
HYDROGENOLYSIS USING RANEY NICKEL AND 2-
PROPANOL
Robert C. Mebane a , Kimberly D. Grimes a , Summer R. Jenkins a , Jonathan D. Deardorff a
Benjamin H. Gross a
&
a Department of Chemistry , University of Tennessee at Chattanooga , Chattanooga, TN,
37403-2598, U.S.A.
Published online: 16 Aug 2006.
To cite this article: Robert C. Mebane , Kimberly D. Grimes , Summer R. Jenkins , Jonathan D. Deardorff & Benjamin H. Gross
(2002) DEIODINATION OF IODOLACTONES BY TRANSFER HYDROGENOLYSIS USING RANEY NICKEL AND 2-PROPANOL, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:13, 2049-2054, DOI:
10.1081/SCC-120004856
To link to this article: http://dx.doi.org/10.1081/SCC-120004856
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SYNTHETIC COMMUNICATIONS, 32(13), 2049–2054 (2002)
DEIODINATION OF IODOLACTONES BY
TRANSFER HYDROGENOLYSIS USING
RANEY NICKEL AND 2-PROPANOL
*
Robert C. Mebane, Kimberly D. Grimes,
Summer R. Jenkins, Jonathan D. Deardorff,
and Benjamin H. Gross
Department of Chemistry, University of Tennessee at
Chattanooga, Chattanooga, TN 37403-2598, USA
ABSTRACT
Raney nickel in refluxing 2-propanol is an effective catalytic
system for reducing iodolactones into their corresponding
lactones.
Key Words: Catalytic transfer hydrogenolysis; Deiodination;
Raney nickel; Iodolactone; Lactone
Iodolactonization of suitable unsaturated carboxylic acids followed by
reductive deiodination constitutes an important synthesis of lactones.[1]
This synthetic methodology has been widely utilized in natural product
synthesis[2] and in the synthesis of complex organic molecules.[3] A number
of different reagents have been used in iodolactonizations and have been
thoroughly summarized by Simonot and Rousseau.[4] Two of the more
common methods[5] for deiodination are metal catalyzed hydrogenolysis with
*Corresponding author. E-mail: Robert-Mebane@utc.edu
2049
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

2050
MEBANE ET AL.
molecular hydrogen[6] and radical cleavage with tri-n-butyl tin hydride.[7]
Although tri-n-butyl tin hydride is an effective reducing agent, there are
toxicological and ecological concerns regarding its use as clearly described
by Chatgilialoglu.[8] In addition, products are often contaminated with trace
organotin compounds which are difficult to remove.[9] A disadvantage to the
metal catalyzed hydrogenolysis procedure is the special handling precau-
tions which must be exercised when using molecular hydrogen.
In this report we describe an attractive alternative to deiodination of
iodolactones which is based on catalytic transfer hydrogenolysis using Raney
nickel and 2-propanol as the hydrogen donor. Raney nickel is widely recog-
nized as a versatile catalyst for effecting reductive transformations of organic
compounds.[10] Less well known and utilized is Raney nickel’s ability to
catalyze reductions using hydrogen donors, such as 2-propanol, instead of
molecular hydrogen.[11] Although the literature is somewhat sparse, Raney
nickel catalyzed transfer hydrogenations utilizing 2-propanol have been
reported for the reduction of olefins,[12] ketones,[12–14] phenols,[12] aromatic
nitro compounds,[15,16] and certain aromatic hydrocarbons.[12,17]
The experimental procedure for the catalytic transfer hydrogenolysis
of iodolactones is simple and straightforward and affords lactones in good
yields. The overall reaction is described in Figure 1 and a summary of our
results is presented in Table 1. Iodolactones previously described in the
literature were used in this study.[18] The yields reported in Table 1 are
isolated yields and represent the average of at least two reactions. Yields
as determined by glc were essentially quantitative. The low isolated yield
observed for lactone 10 may result from our inability to remove the lactone
from the catalyst surface due to a strong adsorptive interaction between the
phenyl group in 10 and the nickel surface.[19] Isolation of lactone 7 was
hindered by its volatility.
The optimal substrate to catalyst ratio found for the hydrogenolysis of
iodolactones was 1 : 10 by weight. This high catalyst loading is necessary
because of the poisoning effect of the HI that is generated in the reaction.
Figure 1. Deiodination by catalytic transfer hydrogenolysis.

DEIODINATION OF IODOLACTONES
2051
Table 1. Catalytic Transfer Hydrogenolysis of Iodolactones with
Raney Nickel and 2-Propanol as the Hydrogen Source
Iodolactone
Lactone
Isolated Yield (%)*
51
60
90
40
78
74
*Average of at least two yields.
The need for higher catalyst ratios when cleaving C–X bonds with Raney
nickel and molecular hydrogen is well documented.[20,21] The catalyst load
could be reduced with the addition of at least one equivalent of base such as
KOH, NaHCO3, Et3N, or pyridine or with the use of ammonium formate[22]
as the hydrogen donor. Good yields of lactones were obtained with the
inclusion of base; however, in all cases minor amounts (5–20%) of

2052
MEBANE ET AL.
ring-opening products were also obtained. Although a high catalyst load
was necessary in our deiodination reactions, we did find that the Raney
nickel catalyst could be reused repeatedly (at least 6ꢀ) after a simple regen-
eration step consisting of refluxing the catalyst in 2-propanol containing
KOH (0.12 g/1 g catalyst used) for 15 min followed by rinsing the catalyst
with cold 2-propanol (3ꢀ).
In conclusion, catalytic transfer hydrogenolysis with Raney nickel and
2-propanol is an effective method for the conversion of iodolactones into
lactones. Furthermore, this environmentally-friendly and inexpensive
method is an attractive alternative to catalytic hydrogenolysis with molecu-
lar hydrogen and the widely used procedure which employs tri-n-butyl tin
hydride.
EXPERIMENTAL
RaneyÕ 2800 nickel was obtained from W.R. Grace Company,
Chattanooga Davison. The catalyst was washed prior to use with distilled
water (6ꢀ) and 2-propanol (3ꢀ) and stored in 2-propanol. 1H NMR spectra
were recorded on a Varian Gemini 300 using tetramethylsilane as internal
reference. IR spectra were recorded on a Nicolet Impact 410 spectrometer.
The IR and NMR spectra of the lactones prepared in this work were
identical to the spectra described in the literature.[23–27]
As an illustrative example of the hydrogenolysis procedure, iodolac-
tone 3 (0.50 g, 2.1 mmol) was refluxed in a magnetically stirred suspension
of Raney nickel (5 g) in 2-propanol (30 mL) for 15 min with the condenser
open to the atmosphere. After cooling to room temperature the organic
layer was decanted from the Raney nickel[28] and the catalyst was washed
with 2-propanol (3 ꢀ 10 mL). The combined organic layers were filtered
through Celite and the solvent was removed by rotary evaporation
and high vacuum to give dihydro-5-ethyl-2(3H)-furanone (9) as an oil in
90% yield. IR (neat) 1770 cmꢁ1
;
1H NMR: d 1.06 (t, J ¼ 7.4 Hz, 3H),
1.63–1.99 (m, 3H), 2.38 (m, 1H), 2.60 (dd, J ¼ 5.9 & 6.59 Hz, 2H), 4.50
(q, J ¼ 6.8 Hz, 1H).[24]
Dihydro-5-methyl-2(3H)-furanone (7). IR (neat) 1765 cmꢁ1; H NMR:
1
d 1.42 (d, J ¼ 6.7 Hz, 3H), 1.82 (m, 1H), 2.40 (m, 1H), 2.55 (t, J ¼ 6.5 Hz,
2H), 4.55 (m, 1H).[24]
Dihydro-3,3,5-trimethyl-2(3H)-furanone (8). IR (neat) 1775 cmꢁ1
;
1H NMR: d 1.23 (s, 3H), 1.25 (s, 3H), 1.39 (d, J ¼ 6.7 Hz, 3H), 1.69
(dd, J ¼ 9.6 & 13.0 Hz, 1H ), 2.16 (dd, J ¼ 6.0 & 14.0 Hz, 1H), 4.55
(m, 1H).[24]

DEIODINATION OF IODOLACTONES
2053
Dihydro-5-phenyl-2(3H)-furanone (10). IR (neat) 1765 cmꢁ1; 1H NMR:
d 2.20 (m, 1H), 2.72 (m, 3H), 5.46 (dd, J ¼ 6.84 & 8.21 Hz, 1H), 7.20–7.45
(m, 5H).[25]
1
2-Oxabicyclo[3.3.0]octan-3-one (11). IR (neat) 1765 cmꢁ1; H NMR: d
1.50 (m, 1H), 1.60–1.84 (m, 4H), 2.0 (m, 1H), 2.25 (d, J ¼ 16.4 Hz, 1H),
2.72–2.85 (m, 2H), 4.96 (dd, J ¼ 5.12 & 7.28 Hz, 1H).[26]
4-Oxatricyclo[4.2.1.03,7]nonan-5-one (12). IR (neat) 1725 cmꢁ1
;
1H NMR d 1.44–1.58 (m, 3H), 1.64–1.75 (m, 2H), 1.92 (m, 1H), 2.41
(bs, 1H), 2.49 (dd, J ¼ 4.88 & 11.31 Hz, 1H), 3.15 (m, 1H), 4.79
(dd, J ¼ 5.17 & 8.12 Hz, 1H).[27]
ACKNOWLEDGMENTS
The authors gratefully acknowledge financial support from the
University of Chattanooga Foundation and the Grote Chemistry Fund.
In addition, we are indebted to the W.R. Grace Company, Chattanooga
for the generous donation of Raney nickel catalyst.
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Received in the USA July 24, 2001