An expeditious route to phosphorus heterocycles based on ring-closing metathesis

Article abstract of DOI:10.1016/S0040-4039(00)01511-2

A convenient route for the synthesis of phosphorus diolefinic templates starting from the bifunctional reagent bis(diisopropylamino)vinylphosphine is presented. Ring closing olefin metathesis on this type of diene substrate revealed that the newly develop

Full text of DOI:10.1016/S0040-4039(00)01511-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 8635–8638
An expeditious route to phosphorus heterocycles based on
ring-closing metathesis
Mattie S. M. Timmer, Huib Ovaa, Dmitri V. Filippov, Gijs A. van der Marel and
Jacques H. van Boom*
Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, PO Box 9502,
2300 RA Leiden, The Netherlands
Received 21 July 2000; revised 24 August 2000; accepted 7 September 2000
Abstract
A convenient route for the synthesis of phosphorus diolefinic templates starting from the bifunctional
reagent bis(diisopropylamino)vinylphosphine is presented. Ring closing olefin metathesis on this type of
diene substrate revealed that the newly developed 4,5-dihydro-imidazol-2-ylidene ruthenium benzylidene
complex 4 is in all aspects superior to the previously developed Grubbs’ catalyst 1. © 2000 Elsevier
Science Ltd. All rights reserved.
Keywords: ring-closing metathesis; phosphitylation; phosphorus heterocycles.
It is well established now that ring-closing olefin metathesis (RCM) is a powerful tool in the
construction of complex organic molecules.1 It also became clear that a successful outcome of
a RCM reaction is not only restrained by the nature of the functional groups, but also by the
number of atoms connecting the double bonds and the substitution pattern of the olefin moieties
in the RCM template. Among the precatalysts developed thus far, only two are commercially
available. One of them, Grubbs’ ruthenium complex 1,2 has found the widest application. The
other one, the oxygen and moisture sensitive molybdenum complex 2,3 proved to be more
effective in the RCM of sterically congested olefins.
* Corresponding author. Tel: +0031 71 5274274; fax: +0031 71 5274307; e-mail: j.boom@chem.leidenuniv.nl
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01511-2

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Recent studies4 revealed that phosphorus containing heterocycles were accessible by RCM
reaction on diolefinic phosphine oxides under the influence of Grubbs’ catalyst (1). The results
of these studies indicated that the outcome was not fully satisfactory in terms of yield and time
duration. Additional advances in catalyst development resulted in the generation of the new
imidazol-2-ylidene-substituted ruthenium-based catalysts 35 and 4.6 Both catalysts display
remarkable higher thermal stabilities and enhanced RCM activities.5,7 Interestingly, catalyst
loadings of as low as 0.05 mol% still proved to be effective in the case of the 4,5-dihydro-imida-
zol-2-ylidene Ru-based complex 4. In addition, it was expected8 that the presence of a saturated
imidazol-2-ylidene ligand as in 4 would lead to higher catalyst activity than in its unsaturated
counterpart 3. Both aspects tipped the balance of using precatalyst 4 in RCM reactions on the
vinylphosphonates 5a–e and the vinylphosphonamides 6a,b.
Herein we report that the dihydroimidazole carbene ruthenium complex 4 is in all aspects
superior to Grubbs’ catalyst 1 in RCM reactions on substrates 5a–e and 6a,b, which in turn were
easily accessible from the bifunctional phosphitylating reagent bis(diisopropylamino)-
vinylphosphine (7).
The preparation of the two types of diene substrates could be readily accomplished, as
depicted below, starting from the known vinylphosphine 7.9 In the case of the symmetrical diene
5a, vinylphospordiamidite 7 was treated with excess allyl alcohol in the presence of 1H-tetrazole
(2 equiv.). In situ oxidation of the resulting intermediate 9 (R1=R2=allyl; lP 165 ppm) with
t-butyl-hydroperoxide gave, after workup and purification, homogeneous vinylphosphonate 5a.
The nonsymmetrical derivatives 5b–e were prepared as follows. 1H-Tetrazole catalyzed the
phosphitylation of benzyl alcohol (1 equiv.) with 7 and the condensation of purified 8
(R1=benzyl; lP 118 ppm) in the presence of 1H-tetrazole (1 equiv.) with a stoichiometric
amount of the unsaturated alcohols R2ꢀOH (R2=allyl, butenyl or
D
-gluco-furanosyl10) led, after
in situ oxidation, to the isolation of compounds 5b–e. Similarly, condensation of 7 under the

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influence of a catalytic amount of 1H-tetrazole (0.1 equiv.), followed by in situ oxidation of the
intermediate phosphoramidite 8 gave, after workup and purification, phosphonamides 6a,b.
In order to explore in more detail the efficacy of catalyst 4, two sets of RCM reactions were
executed on the substrates 5a–e and 6a,b (0.02 M) utilizing 2 mol% of the initial precatalyst 1
or 1 mol% of the new Grubbs’ precatalyst 4 in refluxing dichloromethane. The results of this
study are recorded in Table 1.
Table 1
RCM on substrates 5a–e and 6a,b using precatalysts 1 and 4
In the first instance, it was established that vinylphosphonate 5a was rapidly and quantita-
tively converted into the oxaphosphole 10a11 under the influence of the new catalyst 4. This
finding is in sharp contrast with the earlier reported4e formation of a mixture containing the 5-
(44%) as well as the 7-membered (31%) P-heterocycles in the RCM of 5a in refluxing CH2Cl2
(0.01 M) using 6 mol% Grubbs’ catalyst 1. The higher potency of precatalyst 4 over Grubbs’
precatalyst 1 is also evident from the fast and high yielding conversion, as gauged by 31P NMR,
of the phosphonates 5b–c into the respective 5-membered P-heterocycles 10b and 10c. Similarly,
RCM reaction on the phosphonamide 6a proceeded smoothly resulting in the formation of the
5-membered P-heterocycle 10d. The outcome of the RCM reaction on substrate 5d also reveals
a substantial decrease in time duration of the expected formation of the 6-membered product
10e. A similar tendency prevails in the transformation of the more sterically demanding
substrates 5e and 6b into the cis-fused 5,6-bicyclic derivatives 10f and 10g.

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The results presented in this paper clearly show that the new Grubbs’ precatalyst 4 is highly
effective in performing RCM reactions on vinylphosphonates as well as on vinylphospho-
namides. In addition, the easily accessible bifunctional reagent bis(diisopropylamino)vinyl-
phosphine (7) promises to be of great value in the preparation of highly functionalized and
structurally diverse phosphorus containing diolefinic templates.
Acknowledgements
This work was financially supported by the Council for Chemical Sciences of the Netherlands
Organization for Scientific Research (CW-NWO) and the Netherlands Technology Foundation
(STW).
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1
11. All compounds were fully characterized by H, 13C and 31P NMR and MS. Relevant example: 2-allyloxy-5H-
[1,2]oxaphosphole 2-oxide (10a), 1H NMR (600 MHz, CDCl3): l 7.16 (ddt, 1H, J 46.29 Hz, J 8.53 Hz, J 1.69 Hz),
6.21 (ddt, 1H, J 34.11 Hz, J 8.54 Hz, J 2.42 Hz), 5.96 (ddt, 1H, J 17.12 Hz, J 10.42 Hz, J 5.53 Hz), 5.37 (m, 1H),
5.26 (m, 1H), 4.80 (m, 2H), 4.58 (m, 2H). 31P NMR (243 MHz, CDCl3): l 43.23. 13C NMR (50 MHz, CDCl3):
148.3 (d, J 16.8 Hz), 132.8 (d, J 6.1 Hz), 118.1 (s), 116.9 (d, J 64.7 Hz), 70.6 (d, J 13.7 Hz), l 67.4 (d, J 6.11 Hz).
HRMS (FAB) calcd for C6H9O3P [M+] 160.0289, found: 160.0280.