Pinacolboratamethyl-enetriphenylphosphonium iodide, a new methylene transfer reagent

Article abstract of DOI:10.1081/SCC-120005942

The title compound is easily prepared and reacts with various aldehydes and ketone. The reagent is compatible with free hydroxy groups. Yields with various aldehydes and ketones are in 50- > 99% range. Both aliphatic, aromatic and unsaturated carbonyls react.

Full text of DOI:10.1081/SCC-120005942

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PINACOLBORATAMETHYL- ENETRIPHENYLPHOSPHONIUM
IODIDE, A NEW METHYLENE TRANSFER REAGENT
a
b
Abed Al-Aziz Quntar & Morris Srebnik
a
Department of Medicinal Chemistry and Natural Products , School of Pharmacy , Hebrew
University , 91120, Israel
b
Department of Medicinal Chemistry and Natural Products , School of Pharmacy , Hebrew
University , 91120, Israel
Published online: 16 Aug 2006.
To cite this article: Abed Al-Aziz Quntar & Morris Srebnik (2002) PINACOLBORATAMETHYL- ENETRIPHENYLPHOSPHONIUM
IODIDE, A NEW METHYLENE TRANSFER REAGENT, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 32:16, 2575-2579, DOI: 10.1081/SCC-120005942
To link to this article: http://dx.doi.org/10.1081/SCC-120005942
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 16, pp. 2575–2579, 2002
PINACOLBORATAMETHYL-
ENETRIPHENYLPHOSPHONIUM
IODIDE, A NEW METHYLENE
TRANSFER REAGENT
Abed Al-Aziz Quntar and Morris Srebnik*
Department of Medicinal Chemistry and Natural
Products, School of Pharmacy, Hebrew University,
91120 Israel
ABSTRACT
The title compound is easily prepared and reacts with various
aldehydes and ketone. The reagent is compatible with free
hydroxy groups. Yields with various aldehydes and ketones
are in 50–>99% range. Both aliphatic, aromatic and unsatu-
rated carbonyls react.
Key Words: Methylene transfer; Boron-Wittig reagent
Several attempt to prepare Wittig-type reagents from boron-
phosphorous compounds have been described in the literature, with mixed
[1]
success. The reaction of phosphorous ylides with chloroborates gives an
intermediate, not isolated, thatreactswithbenzaldehyde togivea1,3-dipheny-
[2]
allene, a product identical to that obtained with a-zincated phosphorous
*
Corresponding author. E-mail: msrebni@md2.huji.ac.il
575
2
DOI: 10.1081/SCC-120005942
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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576
QUNTAR AND SREBNIK
[3]
ylides. A diylideborane was obtained by the reaction of a ylide with a
[4]
dichloroborane. These authors also prepared dialkylborylalkylidenephe-
nylphosphoranes and showed that the latter react with polar electrophiles
[
to give deuterated and brominated Wittig reagents. Hydroboration of
5]
phosphoalkenes with either catecholborane or BH L gives C1bridged phos-
3
[6]
phoboranes. The reaction with aldehydes or ketones was not explored. In
a series of papers, Pelter and Smith investigated the activity of hindered
[
7]
boranes and showed that they reacted with aldehydes to give alkenes.
We have recently prepared various C1bridged phosphorous boronates.
[
8]
In this communication we discuss the chemistry of one of the derivatives,
pinacolboratamethylenetriphenylphosphonium iodide, 1.
Compound 1 is easily prepared by the reaction of pinacolboratamethy-
3
lene iodide with PPh . Compound 1 is stable in air and to moisture.
Treatment of 1 with base and either aldehyde or ketone gave alkene
(
Scheme 1).
We assume that the initial step in the reaction involves coordination
of the base with 1. A free ylide-type intermediate may be formed. But we
have not detected this by NMR (Scheme 1). In accordance with Scheme 1,
triphenylphosphine oxide and borate were also detected by GCMS. In the
case of potassium alkoxides, two equiv of base were required and borate
‘‘ate’’ complexes were formed. The use of lithium amides required only one
equiv of base. The reason for the difference in reactivity of the lithium
amides and the potassium alkoxides is not clear. But this aspect of the
reaction is being investigated. The effect of base on methylene transfer
was explored with benzaldehyde and 4-methoxyphenyl cyclopropyl ketone
(
Table 1).
Lithium hexamethyldisilazide (one equiv) and KOC H (two equiv)
2
5
gave the best results with aldehydes. Several ketones did not react
with lithium hexamethydisilazide but did give satisfactory results with
potassium ethoxide generated ‘‘in situ’’. Alkyllithium bases by themselves
were not effective. Less than 5% methylene transfer was detected. Two sets
Scheme 1. Reaction of 1 with carbonyls.

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NEW METHYLENE TRANSFER REAGENT
2577
Table 1. Influence of Base on the Reaction of 1 with Benzaldehyde or Cyclopropyl-
4
-methoxyphenyl Ketone
a
Base
Carbonyl
Yield (%)
Hexamethyldisilazane
Tetramethylenediamine
Tetramethylpiperidine
Diisopropylamine
Potassium methoxide
Potassium ethoxide
Potassium isopropoxide
Potassium t-butoxide
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
4-Methoxyphenyl cyclopropyl ketone
4-Methoxyphenyl cyclopropyl ketone
4-Methoxyphenyl cyclopropyl ketone
4-Methoxyphenyl cyclopropyl ketone
>99
98
98
94
5
90
b
b
b
90
70
b
a
ꢀ
Lithium amide was generated at 0 C with one equiv of n-BuLi.
b
Two equiv of alkoxide were used. One equiv gave only 50% conversion.
of conditions were developed for methylene transfer to aldehydes and ketones.
For all aldehydes lithium hexamethyldisilazide proved sufficient. For certain
ketones better results were obtained with potassium tert-butoxide (Table 2).
Reagent 1 reacts readily with aldehydes to transfer the methylene group.
The reaction works well with both aromatic, aliphatic, and unsaturated
aldehydes. Of particular interest is the fact that the reaction is compatible
with a free hydroxy group, both on aldehydes and ketones, though the latter
gave somewhat reduced yields (Table 2). Competition between aldehyde and
ketone was tested by introducing one equiv of benzaldehyde and acetophe-
none to one equiv of 1. Benzaldehyde was completely converted to styrene.
The reagent was also reacted with esters and epoxides but no methylene
transfer was observed. Only starting materials were recovered. The effect of
solvent was also briefly explored. No reaction was observed in THF, acet-
onitrile, and DMF. In DMSO less than 5% reaction occurred. The solvent
of choice was HMPTA. The advantage that this reagent has over the usual
Wittig reagent is its compatibility with free hydroxy groups, consistently
high yields and conversions for a variety of aldehydes and ketones.
EXPERIMENTAL
Preparation of pinacolboratamethylenetriphenylphosphonium iodide, 1:
Triphenyl phosphine (2.62 g, 10 mL moles) was dissolved in 20 mL of dry
benzene, then pinacolboratamethylene iodide (2.68, 10 mL moles) was
ꢀ
added drop wise at 0 C. The reaction was warmed to room temperature

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578
QUNTAR AND SREBNIK
Table 2. Reaction of 1 with Various Aldehydes and Ketones
Product
a
Aldehyde
Yield (%)
Benzaldehyde
PhCH¼CH
2
99
99
99
99
99
99
99
99
99
2
2
4
-Nitrobenzaldehyde
-Methoxybenzaldehyde
-Methoxybenzaldehyde
2-Nitro-PhCH¼CH
2
2-Methoxy-PhCH¼CH
4-Methoxy-PhCH¼CH
2
2
Cinnamaldehyde
PhCH¼CHCH¼CH
2
2
2
4
3
-Naphthaldehyde
,4-Dichlorobenzaldehyde
NaphthaleneCH¼CH
2
2,4-DichloroPhCH¼CH
2
-Dimethylaminobenzaldehyde 4-DimethylaminoPh¼CH¼CH
2
-Hydroxy-4-methoxy-
benzaldehyde
3-Hydroxy-4-methoxy-PhCH¼CH
C H O
2
1,4-Benzodioxane-6-
carboxaldehyde
90
1
0
10
2
Tetradecenal
Citral
Acetophenone
p-Methoxy acetophenone
Pentadecene
60
99
95
90
85
83
11 18
C H
PhC(CH )CH
2 3
p-OCH
3
PhC(CH
2
)CH
3
3,5-Dimethoxy acetophenone
4- Hydroxy acetophnone
4-Chlorophenyl cyclopropyl
ketone
11 14 2
C H O
4-(OH)PhC(CH )CH
2
3
b
C
11
H
11
90
b
Cyclopropyl-4-methoxyphenyl
ketone
C H O
1
90
2
14
b
50
9
-Fluorenone
C
15
H
12
a
GCMS yield based on an internal standard. Conversion in all cases was >99.
b
2 3
KOCH CH generated ‘‘in-situ’’, 2 equiv was used.
and was stirred overnight. The white precipitate was filtered and washed
ꢀ
with benzene and was dried in vacuum. Yield: 4.2 g, 78%. M.p: 162 C.
1
31
H NMR (CDCl ): ꢀ 1.25 (s, 12 H) 3.2 (d, 2H), 3.63.8 (m, 15H); P NMR
3
1
1
(
CDCl ): ꢀ 22.6. B NMR (CDCl ): ꢀ 21.
3 3
Reaction of benzaldehyde is typical: 0.75 mL of 1.6 M n-BuLi
1.2 mmole) was added dropwise to 0.161 g (1 mmole) of hexamethyl
(
disilazane at 0 C and the mixture was stirred for 2 h. Then 0.53 g of 1 was
ꢀ
added (dissolved in 2 mL of HMPA) and stirred for additional 2 h. The mix-
ꢀ
ture was cooled to ꢁ78 C and 0.02 g of dibromobenzene (internal standard)
followed by 0.106 g (1 mmole) of benzaldehyde were added. The reaction was
warmed gradually to the room temperature and was left stirring overnight at
room temperature. The reaction mixture was worked up with dilute HCl. The

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NEW METHYLENE TRANSFER REAGENT
2579
1
product was extracted with ether and was analyzed by GCMS and H NMR.
All data were compared to authentic samples and found to be indentical.
ACKNOWLEDGMENT
We thank the Israeli Academy of Sciences, the Middle East Cancer
Consortium (MECC) and the Horowitz Foundation for supporting this
research.
REFERENCES
1
. Nikonov, G.N.; Balyeva, A.S. Compounds Containing Phosphorus and
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2
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lithio(trimethylsilyl)methaneboronate, Homologation of Boronic Esters
with[chloro(trimethylsilyl)methyl]lithium, and Comparisons with Some
Phosphorus and Sulfur Analogues. Organometallics 1983, 2, 230–236.
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4
5
¨
. Steiner, M.; Grutzmacher, H.; Prtizkow, H.; Zsolnai, L. a-Zincated
Phosphorus Ylides. Chem. Commun. 1998, 285–286.
. Bestmann, H.J.; Arenz, T. Dialkylboryl-substituted Triphenylphospho-
nium Ylides. Angew. Chem. Int. Ed. Engl. 1984, 23, 381–382.
. Bestmann, H.G.; Arenz, T. Synthese Deuterierter und Brom-
Substituierter Olefine aus Dialkylboryl-Alkylidentriphenylphosphora-
nen. Tetrahedron Lett. 1986, 27, 1995–1998.
6
. Yoshifuji, M.; Takahashi, H.; Toyota, K. Reactions of Sterically
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7. For a Review of their work: Pelter, A. Some Chemistry of Hindered
Organoboranes. Pure Appl. Chem. 1994, 66, 223–233.
8
. Pergament, I.; Srebnik, M. Arbuzov Reaction of 1-Iodoboronates as a
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Lett. 1999, 40, 3895.
Received in the UK June 15, 2001

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