Intramolecular [4 + 2] cycloadditions involving transient phosphaalkene intermediates as dienophiles: A useful entry to phosphabicyclo[4.3.0]non-4-ene derivatives

Article abstract of DOI:10.1039/a708020d

Three representative phosphabicyclo[4.3.0]non-4-ene derivatives are formed in high yields and various diastereomeric forms by [4 + 2] intramolecular cycloadditions involving transient phosphaalkenes as dienophiles; complete diastereoselectivity is observe

Full text of DOI:10.1039/a708020d

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Intramolecular [4 + 2] cycloadditions involving transient phosphaalkene
intermediates as dienophiles: a useful entry to phosphabicyclo[4.3.0]non-4-ene
derivatives
Jean-François Pilard, Annie-Claude Gaumont, Ce´line Friot and Jean-Marc Denis*†
Synthe`se et e´lectrosynthe`se organiques, UMR 6510, Universite´ de Rennes 1, Campus de Beaulieu, F-35042, Rennes, France
Three
representative
phosphabicyclo[4.3.0]non-4-ene
on phosphorus and carbon, (ii) the reduction of esters A into
phosphines B with dichloroalane is chemoselective,8 and (iii)
HCl elimination occurs under mild conditions at a temperature
which depends both on the strength of the base and the P–H
acidity of the phosphine, allowing us to determine the best
conditions for the trapping of the transient phosphaalkene C.
We decided to adopt this strategy for the synthesis of the
phosphabicyclononenes 5a–c (Scheme 2).
derivatives are formed in high yields and various diaster-
eomeric forms by [4 + 2] intramolecular cycloadditions
involving transient phosphaalkenes as dienophiles; complete
diastereoselectivity is observed with the P-substituted de-
rivative.
Free cyclic phosphines and their metal coordination complexes
are valuable intermediates in organophosphorus chemistry.1
They are prepared by many different approaches, among them,
cycloaddition reactions involving CNP double bonds with
dienes and dipoles appear to be of synthetic value.1,2 the main
problem encountered by using this methodology is keeping the
reactivity of the PNC double bond under control. Self-
condensations are usually avoided by steric or electronic effects
and by complexation with a transition metal. Some cycloaddi-
tions lacking stabilisation of the PII intermediate occur in high
yield,3 especially when the cycloadducts spontaneously ar-
omatize, thus giving a useful entry to functionalised phosphi-
nines;4 in most cases however the desired cycloadducts are
accompanied of various amounts of self-condensed products.2d
In order to circumvent this problem we thought to trap the
transient species by internal cycloaddition. Under these condi-
tions, the rates of the reactions are expected to be strongly
enhanced by entropic assistance, hopefully making the self-
condensation reactions of transient species negligible. Inter-
molecular reactions between conjugated dienes and phos-
phaalkenes have been recently reviewed.2a It is now well
established that, with the exception of some derivatives bearing
electronegative substituents, the reaction takes place with
retention of the phosphaalkene stereochemistry. Furthermore, at
least with cyclopentadiene derivatives, the endo preference is
respected with substituents on phosphorus. Thus, the potential
versatility of intramolecular cycloadditions involving low
coordinated phosphorus derivatives as dienophiles should
afford a useful entry to tailored and hopefully stereocontrolled
polycyclic systems. As a first evaluation of this methodology,
we present here the synthesis of three differently substituted
2-phosphabicyclo[4.3.0]non-4-ene phosphines 5a–c by intra-
molecular [4 + 2] cycloadditions involving the corresponding
terminal phosphaalkenes 4a–c as dienophiles. Conditions for
controlling the stereochemistry are described.
Chlorophosphonate 2a was prepared by halogen–metal
exchange of trichloromethylphosphonate [Cl3CP(O)(OEt)2]6
with BuLi (2 equiv.) followed by selective monosilylation
[Me3SiCl (1 equiv.)], alkylation [(E)-1-bromohepta-4,6-diene 1
(1 equiv.)]9 of the resulting lithiated intermediates and sub-
sequent hydrolysis in basic media.10 The phosphonate 2b and
phosphinate 2c were prepared by halogen–metal exchange of
trichloromethylphosphonate [Cl3CP(O)(OEt)2] and trichloro-
methylphenylphosphinate6 [Cl3CP(O)(OEt)Ph]7 respectively
with BuLi (1 equiv.) followed by alkylation of the resulting
intermediates with 1 (Scheme 2). The yields of 2a and 2b were
greater than 85% after purification by chromatography on silica.
The yield for 2c is lower (57%), a small amount of the starting
material 1 being recovered at the end of the reaction.
Chemoselective reduction of esters 2a–c with dichloroalane5,8
in THF afforded the free phosphines 3a–c. The low volatility of
the latter prevents purification by the general procedure
involving successive vacuum transfers.5 The following protocol
was used: after hydrolysis of the crude mixture at 210 °C with
deoxygenated water, the organic solution was filtered off under
a slight pressure of neutral gas, washed again and then dried.
Cl
R1
O
Cl
i, ii
iii
Br
C
P
C
P
R1
R2
H
EtO R2
1
2a R1 = H, R2 = OEt
b R1 = Cl, R2 = OEt
c R1 = Cl, R2 = Ph
3a R1 = R2 = H
b R1 = Cl, R2 = H
c R1 = Cl, R2 = Ph
iv
R1
C
We have recently developed a general route to non-stabilized
phosphaalkenes which involves as a key step the dehy-
drohalogenation of a-chloroalkylphosphines with a Lewis
base2d,5 (Scheme 1). This procedure is attractive for the
following reasons: (i) the a-chlorophosphonate and phosphi-
nate precursors A are readily available by conventional anionic
routes,6,7 allowing introduction of the desired substituents both
R1
R2
P
P
R2
5a R1 = R2 = H
b R1 = Cl, R2 = H
c R1 = Cl, R2 = Ph
4a R1 = R2 = H
b R1 = Cl, R2 = H
c R1 = Cl, R2 = Ph
Scheme 2 Reagents and conditions: i, THF, BuLi (2 equiv. for 2a, 1 equiv.
for 2b,c), 285 °C, then Cl3CP(O)(OEt)2; ii (for 2a), 285 °C, Me3SiCl (1
equiv.), then 285 °C, Br(CH2)3CHNCHCHNCH2, then 20 °C, aq. LiOH;
(for 2b,c), 285 °C, Br(CH2)3CHNCHCHNCH2; iii, ‘AlHCl2’, THF, 280 to
20 °C, then deoxygenated H2O, 210 °C, then MgSO4; iv (for 5a,b),
260 °C, Py (3 equiv.), then 260 to 20 °C; (for 5c) 230 °C, Et3N (2.5
equiv.), then 230 to 20 °C
O
Cl
C
H
P
Cl
C
R1
R3
R2
R3
R2
R3
R2
R1
P
R1
P
C
OEt
A
B
C
Scheme 1
Chem. Commun., 1998
457

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Solutions were used without further purification, and the
chlorophosphines 3a–c were stable in the absence of oxygen.
Yields determinated by NMR spectroscopy with an internal
on the basis of the 2JPC(7) coupling constant: the observed value
(15 Hz) favours a trans relationship between the lone pair and
C(7).3,13,14§ (ii) The cis-fused cycloadduct is proposed to take
into account the preference of the P-substituent for the endo
postions.2a,15,16 The phenyl and chloride substituents in 4c are
consequently in a trans relationship. The 1H, 31P and 13C NMR
data and mass spectra (HRMS) of 5a–c are fully consistent with
their assigned structures.
reference were greater than 70% (purity
> 90%). The
characterisation was supported by HRMS and 31P, 1H and 13
C
NMR data, all of which were consistent with the assigned
structure.‡
We have shown in our previous work that (i) transient
phosphaalkenes are detectable by 31P NMR spectroscopy in the
dehydrochlorination of primary and secondary a-chloro-
alkylphosphines2d,5 under controlled temperature conditions
(from 280 to 20 °C) and (ii) polymerisation of the chloro-
phosphaalkene intermediates was observed in the elimination of
HCl from a,aA-dichlorophosphines by a weak Lewis base
(pyridine) in the absence of a trapping agent.11,12 Whatever the
nature of the Lewis base, we never detected in this work the
expected phosphaalkene intermediates 4a–c starting from 3a–c.
The only observed products were the cycloadducts 5a–c
characterized by new signals in the 31P NMR spectra and the
corresponding JPH couplings: cyclic phosphines 5a and 5b were
observed when the temperature rose to 260 °C in the presented
pyridine (3 equiv.). Due to the lower P–H acidity5 of secondary
phosphines, elimination of HCl from a,aA-chlorophosphine 3c
occurred at 230 °C with a stronger base [NEt3 (2.5 equiv.)].
Intramolecular [4 + 2] cycloaddition of 4a–c with the diene
counterpart is consequently a fast step. Self-condensations are
strongly inhibited, as was confirmed by the high yield of
cycloadducts (i.e. yield for 5c > 80%, determined by 31P NMR
spectroscopy with an internal reference). All these results are
consistent with entropic activation.
In summary, we have shown that intramolecular [4 + 2]
cycloadditions involving phosphaalkenes can be considered as
a potentially useful route for the construction of stereocontrol-
led polycyclic structures bearing a phosphorus atom, with the
entropic effect suppressing the polymerisation of the transient
intermediate. A more detailed mechanistic study of this reaction
is under active investigation.
Footnotes and References
† E-mail: Jean-Marc Denis@univ-rennes1.fr
‡ All new products were characterized by 31P, 1H and 13C NMR
spectroscopy and mass spectrometry (HRMS).
§ The so called ‘cis rule’ (ref. 15) is applied. For tetrahydrophosphinines:
2
2
cis-geometry, JPC = 20–22 Hz; trans-geometry, JPC = 15–16 Hz (refs.
13, 14).
1 L. D. Quin and A. N. Hughes, The chemistry of organophosphorus
compounds, ed. F. R. Hartley, Wiley, Chichester, 1990, vol. 1.
2 (a) F. Mathey, Acc. Chem. Res., 1992, 25, 90; (b) M. Regitz and
P. Binger, Angew. Chem., Int. Ed. Engl., 1988, 27, 1484; (c) R. Appel
and F. Knoll, Adv. Org. Chem., 1989, 33, 258; (d) A. C. Gaumont and
J. M. Denis, Chem. Rev., 1994, 94, 1413.
3 L. D. Quin, A. N. Hughes and B. Pete, Tetrahedron Lett., 1987, 28,
5783.
4 P. Pellon, Y. Y. Yeung Lam Ko, P. Cosquer, J. Hamelin and R. Carrie´,
Tetrahedron Lett., 1986, 27, 5611; P. Le Floch and F. Mathey,
Tetrahedron Lett., 1989, 30, 817.
5 A. C. Gaumont, B. Pellerin, J. L. Cabioch, X. Morise, M. Lesvier,
P. Savignac, P. Guenot and J. M. Denis, Inorg. Chem., 1996, 35, 6667
and references cited therein.
6 P. Coutrot, C. Laurenco, J. F. Normant, P. Perriot, P. Savignac and
J. Villieras, Synthesis, 1977, 615.
7 X. Morise, P. Savignac and J. M. Denis, J. Chem. Soc., Perkin Trans. 1,
1996, 2179.
8 J. L. Cabioch and J. M. Denis, J. Organomet. Chem., 1989, 377, 227.
9 J. A. Marshall, J. Grote and J. E. Audia, J. Am. Chem. Soc., 1987, 108,
1186.
Since cycloaddition reactions take place with retention of
stereochemistry at the PII centre,2a both (Z)- and (E)-phospha-
alkene intermediates are expected from elimination of HCl from
a-chlorophosphines 3, giving four isomeric cycloadducts. The
observed stereochemical course differs strongly with the
structure of the dienophile. We observed a weak selectivity
starting from 4a [four isomers, at d 291.5 (d, 1JPH = 187 Hz),
288.4 (d, 1JPH = 191 Hz), 285 (d, 1JPH = 182 Hz) and 268.7
1
(d, JPH = 178 Hz); ratio = 57:20:14:9, respectively]. A
higher selectivity is encountered for 4b [two isomers at d 276
(1J1PH = 186 Hz) and 265 (1JPH = 195 Hz); ratio = 81:19,
respectively]. These results are consistent with the presence of
the two (Z)- and (E)-phosphaalkene intermediates for 4a and 4b.
On the other hand, intramolecular cycloaddition of 4c is highly
selective, and only one isomer is observed. The stereochemistry
of the P(1), C(8) and C(9) centres is controlled (Scheme 3). (i)
The relative configuration at P and C(8) of 5c was established
10 For a general procedure see M. P. Teulade and P. Savignac,
J. Organomet. Chem., 1988, 338, 295.
11 J. C. Guillemin, M. Le Guennec and J. M. Denis, J. Chem. Soc., Chem.
Commun., 1989, 988.
12 C. Grandin, E. Abbout-Joudet, N. Collignon, J. M. Denis and
P. Savignac, Heteroatom Chem., 1992, 3, 337.
13 M. Abbadi, P. Cosquer, F. Tonnard, Y. Y. Yeung Lam Ko and R. Carrie´,
Tetrahedron, 1991, 47, 71.
14 L. D. Quin and M. J. Gallagher, in Phosphorus-31 NMR Spectroscopy
in Stereochemical Analysis, ed. J. G. Verkade and L. D. Quin, VCH,
Weinheim, 1987.
5
6
H
H
Cl
9
2
4
3
8
7
Cl
15 R. Appel, J. Menzel and F. Knoch, Chem. Ber., 1985, 118, 4068.
16 R. de Vaumas, A. Marinetti, L. Ricard and F. Mathey, J. Am. Chem.
Soc., 1992, 114, 261.
P
P
Ph
1
Ph
4c
5c
Scheme 3
Received in Liverpool, UK, 6th November 1997; 7/08020D
458
Chem. Commun., 1998