Reduction of diaryl alkenes by hypophosphorous acid-iodine in acetic acid

Article abstract of DOI:10.1016/S0040-4020(02)00415-5

A mixture of 50% aqueous H₃PO₂ and I₂ (in catalytic amount) in HOAc efficiently reduces aryl alkenes to the corresponding alkanes in high yield. Addition of acetic anhydride to the medium results in ring-acetylation (or N-acetylation in the case of amines). H₃PO₂ costs only one-fifth as much as hydriodic acid on a mole basis and one mole of H₃PO₂ produces four moles of HI, resulting in a 20-fold cost advantage for H₃PO₂/I₂ over aqueous HI as a source of HI.

Full text of DOI:10.1016/S0040-4020(02)00415-5

TETRAHEDRON
Pergamon
Tetrahedron 58 +2002) 4411±4415
Reduction of diaryl alkenes by hypophosphorous acid±iodine in
acetic acid
Albert J. Fry,p Myron Allukian and Allison D. Williams
Department of Chemistry, Wesleyan University, Middletown, CT 06459, USA
Received 15 January 2002; revised 10 April 2002; accepted 12 April 2002
AbstractÐA mixture of 50% aqueous H3PO2 and I2 +in catalytic amount) in HOAc ef®ciently reduces aryl alkenes to the corresponding
alkanes in high yield. Addition of acetic anhydride to the medium results in ring-acetylation +or N-acetylation in the case of amines). H3PO2
costs only one-®fth as much as hydriodic acid on a mole basis and one mole of H3PO2 produces four moles of HI, resulting in a 20-fold cost
advantage for H3PO2/I2 over aqueous HI as a source of HI. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
reduction of a variety of aryl substituted ethylenic double
bonds by H3PO2/I2 in acetic acid +Eq. +2)).
We reported earlier that hydrogen iodide, regenerated cata-
lytically by a mixture of hypophosphorous acid and iodine,
reduces diaryl ketones and diaryl carbinols to the corre-
sponding diarylmethanes in high yield.1,2 In the course of
that work, we observed that the carbon±carbon double bond
of dibenzosuberenone +1) is reduced, as well as its carbonyl
group, to afford dibenzocycloheptane +2) +Eq. +1)).1 Since
the double bond of 1 is formally conjugated with the car-
bonyl group, and this system is also capable of reducing the
carbon±carbon double bond of a,b-unsaturated ketones,1,3
it was not clear whether other ethylenic double bonds would
be reduced by this system. In the present study we report the
2. Results and discussion
2.1. General
The alkenes examined in this study include trans-stilbene
+3a), 4,40-bis[tri¯uoromethyl]stilbene +3b), 1-phenyl-2-+2-
thienyl)ethylene +3c), triphenylethylene +3d), tetraphenyl-
ethylene +3e), a-methylstilbene +3f), 1,1-diphenylethylene
+3g), 4-dimethylaminostilbene +3h), acenaphthylene +5),
dibenz[c,f]azepine +iminostilbene) +6a), and cyclooctene
+7). Preliminary experiments showed that reduction of the
ethylenic bond of 3a does not take place in dimethylforma-
mide or dimethylsulfoxide, but that the reduction takes
place readily in hot acetic acid. A mixture containing 50%
aqueous hypophosphorous acid, alkene, and iodine in ca.
20:5:4 molar proportion in acetic acid was re¯uxed for
24 h. Analysis was by GC-mass spectrometry +GC±MS)
1
ꢀ1†
and H NMR spectroscopy; it was possible in almost all
cases to compare the spectra of the products and their
GC±MS retention times with authentic samples. A few
alkenes were reduced in deuterated medium by substituting
D3PO2 and DOAc for their protio counterparts, and several
experiments were carried out with added acetic anhydride to
generate a non-aqueous medium. When acetic acid was
completely replaced by acetic anhydride as solvent in the
reduction of 3a, a mixture containing bibenzyl +4a) +69%)
and 1,2-diphenyl-3-butanone4 +8) +31%) was produced +run
2); the identity of 8 was proved by comparison with a
synthetic sample. Control experiments demonstrated that
both hypophosphorous acid and either iodine or hydrogen
iodide are required for reduction of the double bond, as we
previously observed in a study of the reduction of benzo-
phenones to diphenylmethanes.1
+2)
Keywords: hydrogen iodide; hypophosphorous acid; alkenes.
Corresponding author. Tel.: 1860-685-2622; fax: 1860-685-2211;
e-mail: afry@wesleyan.edu
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020+02)00415-5

4412
A. J. Fry et al. / Tetrahedron 58 (2002) 4411±4415
+run 11). A small amount of 5-ethylacenaphthene +9c) was
also produced; we had previously observed that alkyl aryl
ketones are reduced slowly under these conditions.1 We
assume that reduction of 5 precedes acylation. Formation
of 5-acetylacenaphthene +9a) as the major regioisomer of
acetylation is in accord with previous reports on the acyla-
tion of this substance.5,6
Table 1. Reduction of aryl alkenes by hypophosphorous acid±iodine in
acetic acid
Entry
Alkene
Aryl alkane +yield, %)
Other products +yield, %)
1
2
3
4
5
6
7
8
3a
3aa
3b
3c
3d
3e
3f
3g
3h
5
99
68
98
99
97
100b
98
96
0
8 +30)
9
Starting material +100)
Dibenz[c,f]azepine +6a) represents the most complex
chemistry observed in this study. When 6a was subjected
to the standard conditions, a mixture was produced consist-
ing of dihydrodibenz[c,f]azepine +10a) +47%), 9-methyl-
acridine +11) +18%), 9-methyl-9,10-dihydroacridine7,8 +12)
+20%), N-acetyldihydrodibenz[c,f]azepine +10b) +9%), and
two compounds produced in too small amounts to isolate, of
mass 223 +4%) and 221 +2%), respectively.
10
11
12
13
98
52
8
5c
9a +40); 9b +3); 9c +5)
11 +92)
12 +20); 11 +18); 10b +9);
unk +4); unk +2)
Cyclooctyl iodide +100)
6
6b
47
14
7
0
50% aq. HPO/I/alkeneˆ20:5:4 in acetic acid at re¯ux for 24 h.
a
Acetic anhydride as solvent.
96 h required for reduction.
Suf®cient acetic anhydride added to reaction mixture to destroy all water.
b
c
One series of experiments involved sampling the composi-
tion of the reaction mixture from the reduction of stilbene
+3a) as a function of time. After 5 min, the mixture
contained three components, bibenzyl +4a), unreacted 3a,
and a-iodobibenzyl +13) in a trace:95:5 ratio. After
15 min, the ratios 4a/3a/13 were trace:91:8. At 60 min,
these ratios amounted to 15:49:36. At the end of 24 h, the
only constituent of the mixture was 4a.
The results +Table 1) demonstrate that the carbon±carbon
double bond of most diarylethylenes is reduced in good
yield by this reagent system. Runs 9 and 12 show that the
presence of a basic nitrogen retards reduction, presumably
by protonation by hydrogen iodide to produce a charged
form of the substrate. Con®rmation that electron-withdraw-
ing substituents do indeed retard reduction was found in a
competition experiment in which an equimolar mixture of
3a and b was reduced at 1008C. A sample taken after 1 h
showed 6% of 4a but only a trace of 4b; after 1.5 h, the ratio
of 4a to b was 27:7. Since even 3d was reduced ef®ciently,
the long reaction time required to reduce 3e is probably due
to its low solubility in the reaction medium. The failure of
cyclooctene +7) to undergo reduction +run 14) demonstrates
the need for aryl substitution for reduction to occur and is
therefore mechanistically signi®cant +see below). The fact
that 3h is not reduced +entry 9) probably arises because the
dimethylamino groupis protonated in this medium, making
the groupstrongly electron-withdrawing.
2.2. Deuteration
Experiments involving deuterated reagents proved to be
quite informative. A reaction mixture containing stilbene
in deuterated hypophosphorous acid +in D2O) and acetic
acid-d was sampled during reaction and analyzed by mass
spectrometry. After 1 h the small amount of bibenzyl
produced had mostly incorporated two deuterium atoms,
with a small amount of d3 content. However, after 6 h
there was ca. 30±35% of d3 and 4±5% of d4 content in
the bibenzyl. Likewise, stilbene present in the solution
after 1 h consisted of mostly d0 with ca. 20% d1 material
and 3±5% 2, but after 6 h the isotopic content of the
unreacted stilbene was approximately 40:40:20 d0/d1,d2.
Thus, though reduction should result in addition of two
deuterium atoms across the double bond, as reaction
proceeds the alkene incorporates an increasing amount of
deuterium, resulting in overall addition of more than two
deuteriums. As a matter of fact, 1H NMR spectroscopy and
Inclusion of acetic anhydride in the medium resulted in
acetylation +runs 2, 11, and 13). Thus, whereas reduction
of the ethylenic bond of acenaphthylene +5) proceeds in
quantitative yield under the standard conditions +run 10),
addition of acetic anhydride to the reaction results in forma-
tion of substantial amounts of acetylacenaphthenes 9a and b

A. J. Fry et al. / Tetrahedron 58 (2002) 4411±4415
4413
Scheme 1.
mass spectrometry showed that 1,1-diphenylethylene +3g)
affords 1,1-diphenylethane containing four deuterium atoms
per mole +14) when subjected to the same reaction
conditions.
On the other hand, alkenes which exchange deuterium
rapidly compared to the rate of reduction should incorporate
deuterium to the maximal degree. 1,1-Diphenylethylene
+3g) exempli®es this situation; exchange is apparently fast
because of the high stability of the doubly benzylic tertiary
carbocation +15) produced by protonation of 3g, and hence
the product +14) is totally deuterated.
The ®rst step in the reduction process is undoubtedly proto-
nation of the carbon±carbon double bond. This hypothesis
is supported by the fact that electron-withdrawing sub-
stituents retard reaction +the competition experiment
between 3a and b already referred to and also run 9, since
the amino groupof 3h is undoubtedly largely protonated in
our medium). Further suggestive evidence for protonation
of the alkene comes from the deuterium exchange observed
with deuterated reagents. As Scheme 1 demonstrates, the
actual amount of deuterium incorporated into the alkane
depends upon the relative rates of exchange and reduction.
If reduction is slow relative to exchange, two deuterium
atoms will be introduced into the product. This situation is
approximated in the early stages of reduction of stilbene;
however, as reaction proceeds the stilbene begins to incor-
porate signi®cant amounts of deuterium and the resulting
bibenzyl is deuterated to a correspondingly higher degree.
Formation of iodide 13 as an intermediate during the reduc-
tion of stilbene, presumably by trapping of carbocation 16
by iodide, raises an intriguing mechanistic question: Is 13 on
Scheme 2.

4414
A. J. Fry et al. / Tetrahedron 58 (2002) 4411±4415
the reaction path to alkane or is it simply involved in a side
equilibrium off the main reduction route? Both possibilities
are shown in Scheme 2. Iodide ion could reduce 13 by either
an electron-transfer radical mechanism +path A) or by direct
displacement on iodine to afford a carbanion which is subse-
quently protonated +path B). Alternatively, formation of 16
could be reversible and 16 itself could be the actual inter-
mediate which is reduced. This could readily occur by elec-
tron transfer between iodide ion and 16 +path C), since
iodide is readily oxidized and benzyl cations are relatively
easily reduced.9 The failure of cyclooctene +7) to be reduced
could be understood in terms of any of these possibilities: it
should be protonated less readily than the aryl alkenes and
the resulting iodide would be both harder to reduce and less
likely to reionize to the carbocation than a benzylic
iodide10,11 The formation of ketone 8 from the reduction
of stilbene in the presence of acetic anhydride might be
construed as evidence for a carbanion intermediate which
attacks acetic anhydride nucleophilically. On the other hand
it is possible that 8 is produced by electrophilic acylation of
the carbon±carbon double bond of 3a, followed by reduc-
tion of the double bond of the resulting a,b-unsaturated
ketone by HI.
300 MHz spectrometer. GC-MS analysis was carried out
on a Hewlett±Packard Model 5850 instrument. Flash
chromatographic separations were carried out using Merck
230±400 mesh silica gel. Preparative scale thin layer chro-
matography was performed on 1000 mm silica gel plates.
All products are known compounds and their NMR and
mass spectra were compared with authentic commercial
samples and/or with spectra in the literature.
4.1.1. 1-Phenyl-2--2-thienyl)ethylene -3c).16 To 1.2 g
+2.4 mmol) of Aldrich `Instant Ylide' +a benzyltriphenyl-
phosphonium bromide±sodium amide dry mixture) was
added 2 mL of dry THF. 2-Thiophenecarboxaldehyde
+0.19 mL, 1.9 mmol) was added to the bright orange solu-
tion. After 15 min stirring, the mixture had turned to a light
brown color. After quenching with 2.0 mL of 25% aq.
NaOH and neutralization with 6.0 mL of 0.1 M HCl and
extraction with ether, the ether was dried over Na2SO4 and
evaporated. Flash chromatography removed triphenyl-
phosphine oxide and afforded 3c +0.22 g, 63%) as a 2:3
cis/trans mixture.
4.1.2. trans-4-Dimethylaminostilbene -3h).17 Alkene 3h
was synthesized by the same procedure as in the preceding
paragraph except for substitution of 4-dimethylamino-
benzaldehyde. The product was isolated as bright orange
crystals in 54% yield.
The conversion of dibenz[c,f]azepine +6a) to 9-methyl-
acridine +11) +which is presumably then reduced to 12), in
which one of the vinyl carbons of 6 ultimately becomes a
methyl group, is unusual but precedented. Both amine 6a
and its N-acyl derivative 6b are converted into 11 when
heated in acid12,13 Amide 6b is clearly unusual elec-
tronically: for example, it does not undergo hydrolysis to
6a under conditions +acid or base) under which 10b is
readily hydrolyzed;14 this and its UV spectrum14 and crystal
structure15 all indicate that the electrons on nitrogen do not
interact with the ring, probably because such overlap would
produce a HuÈckel 8-electron antiaromatic system.
4.2. Representative procedure for reduction of alkenes
Iodine +1 g, 4 mmol) and stilbene +3a) +1.0 g, 5.56 mmol)
were added to 25 mL of acetic acid and the solution was
¯ushed with nitrogen. Hypophosphorous acid +50% aq.,
2 mL, 19.3 mmol) was added and the solution was heated
to re¯ux. After 24 h, the mixture was quenched with 50 mL
water and extracted with benzene. The organic extracts were
washed successively with aq. NaHCO3 and aq. NaHSO3,
dried over MgSO4, and evaporated. Analysis by GC±MS
demonstrated that the colorless solid +0.99 g, 99%)
consisted of bibenzyl +4a) in 100% purity.
3. Conclusion
The results demonstrate that a mixture of hypophosphorous
acid and iodine in acetic acid ef®ciently reduces aryl alkenes
to the corresponding alkanes, which are obtained in high
purity. Although the reaction is broadly applicable, reduc-
tion is slow in the presence of basic sites. Addition of acetic
anhydride to the medium results in ring-acetylation +or
N-acetylation in the case of amines). Although the actual
reductant in these reactions is undoubtedly hydrogen iodide
produced by reaction between the two, this reaction system
has advantages over aqueous hydrogen iodide. Because of
the lower water content, H3PO2/I2 reductions generally
proceed more rapidly than with aqueous HI,1 and not only
does aqueous HI cost ®ve times as much as H3PO2, but one
mole of H3PO2 produces four moles of HI,1 resulting in a
20-fold cost advantage for H3PO2/I2 over aqueous HI as a
source of HI.
4.3. Reduction of 3a in acetic anhydride
Reduction was carried out as in the preceding paragraph,
except for substitution of acetic anhydride for acetic acid.
Product analysis by GC±MS showed two products: bibenzyl
+4a) +69%) and 1,2-diphenyl-3-butanone +8) +31%). A
comparison sample of the latter substance was prepared
by K2CrO7/H2SO4 oxidation of 1-phenyl-2-propanol
followed by phase-transfer benzylation of the resulting
1-phenyl-2-propanone by a literature procedure.4
Acknowledgements
4. Experimental
4.1. General
Financial support from the National Science Foundation
under grants CHE-97-13306 and CHE-0100727 is gratefully
acknowledged. Allison Williams received a summer under-
graduate research fellowshipfrom NSF-REU grant CHE-
9820182 for the summer of 2001.
1H NMR spectra were recorded in CDCl3 on a Varian

A. J. Fry et al. / Tetrahedron 58 (2002) 4411±4415
4415
9. Meyers, C. Y.; Hou, Y.; Lut®, H. G.; Saft, H. L. J. Org. Chem.
1999, 64, 9444.
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