Versatile cycloaddition reactions of 1-alkyl-1,2-diphospholes

Article abstract of DOI:10.1080/10426507.2012.744017

The reactivity of 1-alkyl-1,2-diphospholes in cycloaddition reactions with dienes, dienophiles or 1,3-dipoles was examined. 1-Alkyl-1,2-diphospholes (2) exhibit dual reactivity and act as diene toward maleic acid derivatives or as dienophiles with 2,3-dimethyl-1,3-butadiene. The 1-alkenyl-1,2-diphospholes (4) are readily involved in intramolecular [4 + 2] cycloaddition reactions leading to cage phosphines (5). Interaction of 1-alkyl-1,2-diphospholes (2) with 1,3-dipolar reagents (diphenyldiazomethane and nitrones) results in formation of the bicyclic phosphiranes (8) and dimers of 1-alkyl-1,2-diphosphole oxides (9) or bicyclic phosphine oxides (10) with a β-lactam moiety depending on temperature.

Full text of DOI:10.1080/10426507.2012.744017

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Phosphorus, Sulfur, and Silicon and the Related
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Versatile cycloaddition reactions of 1-alkyl-1,2-
diphospholes
Almaz Zagidullin a , Yulia Ganushevich a , Vasili Miluykov a , Oleg Sinyashin a & Evamarie Hey-
Hawkins b
a A. E. Arbuzov Institute of Organic and Physical Chemistry of the Russian Academy of
Sciences, Arbuzov Str., 8, 420088, Kazan, Russia
b Institut für Anorganische Chemie, Universität Leipzig, Johannisallee 29, 04103, Leipzig,
Germany
Accepted author version posted online: 15 Nov 2012.
To cite this article: Almaz Zagidullin , Yulia Ganushevich , Vasili Miluykov , Oleg Sinyashin & Evamarie Hey-Hawkins (2012):
Versatile cycloaddition reactions of 1-alkyl-1,2-diphospholes, Phosphorus, Sulfur, and Silicon and the Related Elements,
DOI:10.1080/10426507.2012.744017
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Versatile cycloaddition reactions of 1-alkyl-1,2-diphospholes
Almaz Zagidullin,1* Yulia Ganushevich,1 Vasili Miluykov,1 Oleg Sinyashin1 and Evamarie Hey-
Hawkins2
1A. E. Arbuzov Institute of Organic and Physical Chemistry of the Russian Academy of Sciences,
Arbuzov Str., 8, 420088 Kazan, Russia. E-mail: zagidullin@iopc.ru; Fax: +7-843-273-18-72
2Institut für Anorganische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig,
Germany
Abstract Reactivity of 1-alkyl-1,2-diphospholes in cycloaddition reactions with dienes,
dienophiles or 1,3-dipoles was examined. 1-Alkyl-1,2-diphospholes (2) exhibit dual reactivity
and act as diene toward maleic acid derivatives or dienophiles with 2,3-dimethyl-1,3-butadiene.
The 1-alkenyl-1,2-diphospholes (4) are readily involved into intramolecular [4+2] cycloaddition
reactions leading to cage phosphines (5). Interaction of 1-alkyl-1,2-diphospholes (2) with 1,3-
dipolar reagents (diphenyldiazomethane and nitrones) results formation of the bicyclic
phosphiranes (8) and dimers of 1-alkyl-1,2-diphosphole oxides (9) or bicyclic phosphine oxides
(10) with β-lactam moiety depending on temperature.
Keywords polycyclic phosphines; 1-alkyl-1,2-diphospholes; cycloaddition reactions;
phosphorus heterocycles
1
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Polycyclic and cage phosphines on the basis of the phosphanorbornene and
phosphanorbornadiene framework are regarded as weak, highly space filling ligands with a
bridgehead non-racemizable chiral phosphorus center in homogeneous, biphasic and asymmertic
catalysis. Representative examples of polycyclic phosphorus compounds are provided by
PennPhos[i], BIPNOR[ii], NORBOS[iii], phosphanorbornadiene diimines[iv], trycyclic
phosphinites[v], P5-deltacyclenes[vi], which have been successfully used as enantiopure ligands for
asymmetric catalysis. This phosphines are competitive with the best ligands proposed in the
literature in terms of both activity and enantioselectivity[vii], [viii]
.
From a synthetic standpoint, such polycyclic phosphines are readily accessible via
cycloaddition reactions of phospholes with different alkenes and alkynes. Most studied are
cycloaddition reactions of two tautomeric forms of monophospholes - 1H- and 2H-phospholes[ix].
Typically 1H-phospholes are thermally stable and act rather as poor dienes toward classic
dienophiles[x] due to residual aromaticity[xi], whereas 2H-phospholes are much less stable and
demonstrate high activity in cycloaddition reactions[xii]. In this manner are of special interest the
1-alkyl-1,2-diphosphacyclopenta-2,4-dienes (1-alkyl-1,2-diphospholes) (2) combining structural
elements both of 1H- and 2H-phospholes. Herein we will summarize our results in the field of
cycloaddition reactions of 1-alkyl-1,2-diphospholes with different dienes, dienophiles and 1,3-
dipolar reagents.
Ph
Ph
R
P
Alk
P
Ph
P
P
R
2H-phosphole
1H-phosphole
1-alkyl-1,2-diphosphole
2
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The 1-alkyl-1,2-diphospholes (2) are readily available by alkylation of sodium 3,4,5-
triphenyl-1,2-diphosphacyclopentadienide (1) with alkyl bromides or iodides (scheme 1)[xiii]
.
Surprisingly, the 1-alkyl-1,2-diphospholes (2) reveal a great thermal stability like 1H-phospholes
- dimerization reaction of (2) was observed only at heating up to 1900С leading to the tricyclic
product (3) of [2+2] cycloaddition reaction of 1,2-diphospholes[xiv] formed by R[1,5]-shift of
alkyl group.
At the same time stability of 1-alkenyl-1,2-diphospholes (4) obtained by alkylation of
sodium 3,4,5-triaryl-1,2-diphosphacyclopentadienide (1) with Br(CH2)nCH=CH2 depends on the
length of alkyl chain (scheme 1). Thus, (1) reacts with allyl bromide or 6-bromo-1-hexene to
give the corresponding 1-alkenyl-1,2-diphospholes (4a, d) which undergo [4+2] intermolecular
cycloaddition reactions to form polymeric compounds. However, alkylation of (1) with 4-
bromo-1-butene or 5-bromo-1-pentene proceeds highly regioselectively with the formation of
cage phosphines (5b, c) in 75-80% yields at room temperature, which are the products of
intramolecular [4+2] cycloaddition reactions of corresponding 1-alkenyl-1,2-diphospholes (4b,
c)[xv]. It should be noted that the intramolecular [4+2] cycloaddition reaction of 1-
butenylphosphole proceed with moderate yield only at heating up to 160°C in xylene for 10–12
h[xvi]. Thus 1-alkyl-1,2-diphospoles (1) seems to be an analogue both 1H- and 2H-phospholes.
Indeed 1-alkyl-1,2-diphospholes (2) react with maleic acid derivatives in mild conditions
to give the corresponding [4+2] cycloaddition products (6) in 80-95% yields (scheme 2). Only
anti-endo-isomer of 1.7-diphosphanorbornene against 4 possible was formed. It should be noted
that the similar [4+2] cycloaddition reaction for 1,2,5-triphenylphosphole with maleic acid
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derivatives proceed at elevated temperatures with low yields (3-11%) and forming of mixture of
two isomers[xvii]
.
Moreover as stable analogues of 2H-phospholes, 1-alkyl-1,2-diphospholes (2) exhibit
dual reactivity and can also act as dienophiles. Thus, 1,2-diphospholes (2) react with 2,3-
dimethylbutadiene-1,3 at room temperature to give 9-alkyl-3,4-dimethyl-6,7,8-triphenyl-1,9-di-
phosphabicyclo[4.3.0]nona-3,7-dienes (7) in 80 % yields[xviii]
.
At the same time, 1,3-dipolar cycloaddition reactions of monophospholes have been
poorly studied in contrast to their Diels–Alder reactions[xix]. Therefore, it was interesting to study
the reactivity of 1-alkyl-1,2-diphospholes (2) toward different 1,3-dipoles
–
diphenyldiazomethane and nitrones. We have found that 1-alkyl-1,2-diphospholes (2) react with
diphenyldiazomethane cleanly at room temperature to form 2-alkyl-3,4,5,6,6-pentaphenyl-1,2-
diphosphabicyclo-[3.1.0]hex-3-enes dienes (8) in 70-75 % yields.
While 1-alkyl-1,2-diphospholes (2) demonstrate similar behavior in reactions with
diphenyldiazomethane like other heterophospholes[19], reactions of (2) with nitrones are more
complicated. At room temperature only dimer of 1-alkyl-1-oxo-1,2-diphospholes (9) are obtained
in 70-80% yield. Probably nitrones act as mild oxidant leading to unstable oxides of 1-alkyl-1,2-
diphospholes, which immediately undergo [4+2] cycloaddition reactions to yield compounds (9).
However at elevated temperature reaction of (2) with nitrones lead to bicyclic phosphine oxides
(10) with β-lactam moiety. Formation of (10) takes place also in an independent reaction of (9)
with nitrones[xx]
.
In summary, we have demonstrated that 1-alkyl-1,2-diphospholes combine the properties
of both 1H-phospholes (thermal stability) and 2H-phospholes (high and dual reactivity in
4
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cycloaddition reaction). Bi-, tricyclic and cage phosphines 5-9 are accessible in high yields (75-
95%) as pairs of enantiomers. This reactions proceed in mild conditions (25°C, 6-12h) with high
regio- and stereoselectivity, which open new possibilities to construct new chiral polycyclic
phosphines with chiral bridgehead phosphorus atoms for asymmetric catalysis [2], [7]
.
Ar
Ar
Ar
Ar
Ar
Ar
Ar
1900C
P
P
RHal
R
P
P
P
P
R [1,5]
[2+2]
Ar
Ar
R
P
P
Na
Ar
Ar
(1)
(2)
R
Ar
(3)
250C, n=1, 4
Polymers
Intermolecular
[4+2]
Ar
Ar
Br
(CH2)n
P
Ar
P
Ar
(CH2)n-1
Ar
(CH2)n
P
P
250C, n=2, 3
Ar
Intramolecular
[4+2]
(4a-d)
(5a-d)
R = Me, Et, n-Pr, i-Pr, n-Bu, i-Bu, Cy
Ar = Ph, p-MeC6H4, p-FC6H4
n = 1 (a), 2 (b), 3 (c), 4 (d)
Scheme 1. Synthesis and thermal stability of 1-alkyl-1,2-diphospholes.
5
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Ph
Ph
R
X
P
P
Ph
O
O
Ph
Ph
P
O
P
[4+2]
[2+4]
R
(7)
Ph
250С
250С
X
R
O
O
(6)
P
P
Ph
Ph
Ph
Ph
250С
R
P
P
Ph
R
P
P
O
Ph
Ph
Ph
(2)
Ph
Ph
O
N
Ph
Ph
Ph
(9)
Ph
Ph
P
Ph
R'
Ph2CN2
P
R
Ph
R' = t-Bu, Ph
Ph
[3+2]
250С
(8)
Ph
1000С
P
N
P
R'
R
O
R = Et, n-Pr, i-Pr, n-Bu, i-Bu
X = O, NH
O
(10)
Scheme 2. Reactivity of 1-alkyl-1,2-diphospholes toward dienes, dienophiles and 1,3-dipolar
reagents.
6
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References
[i] Zhang, Z.; Zhu, G.; Jiang, Q.; Xiao, D.; Zhang, X. J. Org. Chem. 1999, 64, 1774-1775.
[ii] Robin, F.; Mercier, F.; Ricard, L.; Mathey, F.; Spagnol, M. Chem. Eur. J. 1997, 3, 1365-
1369.
[iii] Herrmann, W.A.; Kohlpaintner, C.W.; Manatsberger, R.B.; Bahrmann, H.; Kottmann, H. J.
Mol. Catal. A. 1995, 97, 65-72.
[iv] Germoni, A.; Deschamps, B.; Ricard L.; Mercier F.; Mathey F. J. Organomet. Chem. 2005,
690, 1133-1139.
[v] Clochard, M.; Mattmann, E.; Mercier, F.; Ricard, L; Mathey, F. Org. Lett. 2003, 5, 3093-
3094.
[vi] Hofmann, M.; Hohn, C.; Heinemann, F.W.; Zenneck, U. Chem. Eur. J. 2009, 15, 5998-6007.
[vii] Gilbertson, S.R.; Genov, D.G.; Rheingold A.L. Org. Lett. 2000, 2, 2885-2888.
[viii] Neibecker, D.; Reau, R.; Angew. Chem. Int. Ed. 1989, 28, 500-501.
[ix] Mathey, F. Acc. Chem. Res. 2004, 37, 954-960.
[x] Keglevich, G.; Trecska, M.; Dajka, B.; Pete, B.; Dobo, A.; Toke, L. Heteroat. Chem. 2000,
11, 271-275.
[xi] Nyula`szi, L. Chem. Rev. 2001, 101, 1229-1246.
[xii] Mathey, F. Chem. Rev. 1988, 88, 429-453.
7
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[xiii] Miluykov V.A.; Bezkishko I.A.; Zagidullin A.A.; Sinyashin, O.G., Hey-Hawkins E. Russ.
Chem. Bull. Int. Ed. 2010, 59, 1206-1210.
[xiv] Miluykov, V.; Kataev A.; Sinyashin, O.; Lonnecke, P.; Hey-Hawkins, E. Mend. Commun.
2006, 16, 204-206.
[xv] Zagidullin, A.A.; Miluykov V.A.; Krivolapov, D.B.; Kharlamov, S.V.; Latypov, S.K.;
Sinyashin, O.G.; Hey-Hawkins, E. Eur. J. Org. Chem. 2011, 25, 4910-4918.
[xvi] Mattmann, E; Mercier, F.; Ricard, L.; Mathey, F. J. Org. Chem. 2002, 67, 5422–5425.
[xvii] Mathey, F. Mercier, F. Tetrahedron Lett. 1981, 22, 319-322.
[xviii] Miluykov, V.; Bezkishko, I.; Zagidullin, A.; Sinyashin, O.; Lönnecke, P.; E. Hey-
Hawkins, Eur. J. Org. Chem. 2009, 8, 1269-1274.
[xix] Bansal, R.K.; Kumawat S.K. Tetrahedron. 2008, 64, 10945-10976.
[xx] Zagidullin, A.; Ganushevich, Y; Miluykov, V.; Krivolapov, D.; Kataeva, O.; Sinyashin, O.;
Hey-Hawkins E. Org. Biomol. Chem. 2012, 10, 5298–5306.
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