First iminodiazaphospholidines with a stereogenic phosphorus center. Application to asymmetric copper-catalyzed cyclopropanation

Full text of DOI:10.1021/ja984295g

J. Am. Chem. Soc. 1999, 121, 5807-5808
5807
Scheme 1. Synthesis of Iminophosphoranes 3, 6, and 6b
First Iminodiazaphospholidines with a Stereogenic
Phosphorus Center. Application to Asymmetric
Copper-Catalyzed Cyclopropanation
Jean Michel Brunel, Olivier Legrand, Se´bastien Reymond, and
Ge´rard Buono*
Ecole Nationale Supe´rieure de Synthe`ses
de Proce´de´s et d’Inge´nierie Chimiques d’Aix Marseille
UMR CNRS 6516, Faculte´ de St Je´roˆme
AV. Escadrille Normandie Niemen
13397 Marseille, Cedex 20, France
ReceiVed December 14, 1998
Iminophosphoranes have been extensively used for the high
yield syntheses of a large variety of imines.1-5 Although tri-
phenylphosphine was usually used because of the stability of the
resulting iminophosphorane, the reaction can be performed with
a wide variety of phosphines, including trialkylphosphines,6 mixed
alkylarylphosphines,7 unsaturated phosphines,8 aminophosphines,9
tris(dialkylamino)phosphines,10 cyclic phosphines,11 or bicyclic
phosphines.12 Nevertheless, although iminophosphoranes of gen-
eral structure R3PdN-R′ possess a donor position at the nitrogen
atom capable of metal complexation,13 few chiral versions have
been envisaged and applied in catalytic asymmetric synthesis.7,14
We report here the first diastereoselective synthesis of new
chiral iminodiazaphospholidines bearing the chirality at the chain
and at the phosphorus atom and their use as ligands in an
enantioselective copper-catalyzed cyclopropanation reaction.
Chiral iminophosphorane 3 issued from (R,R)-N,N′-dimethyl-
cyclohexane-1,2-diamine 1 was synthesized in 63% yield by
treatment with phenyl azide in THF at -78 °C of the correspond-
ing phosphine 2 (Scheme 1).
The first chiral iminophosphoranes 6a,b possessing a stereo-
genic phosphorus center were easily prepared from the corre-
sponding diastereomerically pure phosphines 5a,b15 according to
the procedure described above in 61 and 48% yields, respectively
(Scheme 2).
Iminophosphoranes 3, 6a, and 6b are crystalline compounds
characterized by standard methods, including 31P NMR spectros-
copy (δ 19.09, 14.57, and 14.94, respectively in CDCl3).
Moreover, the structure of compound anti-6a was determined by
a single X-ray diffraction study (Figure 1). The P-N2 bond length
Scheme 2. Possible Mechanism for the Stereoselective
Formation of Iminophosphorane 6a
[1.544(3) Å] is within the expected values.2,16 The P-N-Ph bond
angle value is 126.4°, consistent with the proposed sp2 hybridiza-
tion of nitrogen. The molecular structure unambiguously showed
that the configuration at the phosphorus atom was retained during
the nucleophilic attack by the phosphine on the terminal γ-nitrogen
of the azide. Indeed, it is clearly established that this reaction
proceeds through the formation of a linear phosphazide 7a, usually
not detectable, which then dissociates to iminophosphorane,
probably via a four-centered transition state 7b.17
The total retention of absolute configuration at the phosphorus
atom may be interpreted through a mechanism involving a trigonal
bipyramidal intermediate (TBP). The nucleophilic addition of
diazaphospholidine 5a on phenylazide led to the formation of
betain 7a. In this case, elimination of molecular nitrogen may
occur only from TBP intermediates 7b and 7c according to the
principle of microscopic reversibility.18 Considering these as-
sumptions, the R-nitrogen atom may attack at one of the adjacent
faces of the tetrahedron of 7a, in line to one of the nitrogen atoms
of the diazaphospholane ring leading to 7b TBP intermediate in
which the four- and the five-membered rings adopt an axial-
equatorial position. On the other hand, for this TBP intermediate
7b it is possible to consider a low-energy Berry pseudorotation19
leading to the formation of 7c in which the R-nitrogen atom adopts
(1) Staudinger, H.; Meyer, J. HelV. Chim. Acta 1919, 2, 635.
(2) For reviews dealing with Staudinger reaction, see: (a) Gololobov, Y.
G.; Zhmurova, I. N.; Kasukhin, L. F. Tetrahedron 1981, 37, 437. (b) Johnson,
A. W. Ylides and Imines of Phosphorus, Iminophosphoranes and Related
Compounds; John Wiley & Sons: New York, 1993.
(3) Gololobov, Y. G.; Kasukhin, L. F. Tetrahedron 1992, 48, 1353.
(4) Scriven, E. F. V.; Turnbull, K. Chem. ReV. 1988, 88, 298.
(5) For recent applications, see: (a) Molina, P.; Aller, E.; Lorenzo, A.
Synthesis 1998, 283. (b) Okawa, T.; Kawase, M.; Eguchi, S. Synthesis 1998,
1185. (c) Takahashi, M.; Suga, D. Synthesis 1998, 986.
(6) (a) Birkofer, L.; Kim, S. M. Chem. Ber. 1964, 97, 2100. (b) Urpi, F.;
Vilarrasa, J. Tetrahedron Lett. 1986, 27, 4623.
(7) Wilson, S. R.; Pasternak, A. Synlett 1990, 199.
(8) Baechler, R. D.; Blohm, M.; Rocco, K. Tetrahedron Lett. 1988, 29,
5353.
(9) (a) Vetter, H. J.; Noth, H. Chem. Ber. 1963, 96, 1308. (b) Wilburn, J.
C.; Nielson, R. H. Inorg. Chem. 1977, 16, 2519.
(10) Schwesinger, R. Angew. Chem., Int. Ed. Engl. 1987, 26, 1164.
(11) Baccolini, G.; Todesco, P. E.; Bartoli, G. Phosphorus Sulfur 1981,
10, 387.
(16) Two nitrogen atoms N3 and N5 display different P-N bonds length
against P-N4 (P-N3 1.686 Å, P-N5 1.633 Å, and P-N4 1.655 Å,
respectively). Moreover, nitrogen atoms N3 and N5 are essentially coplanar
(sum of angles around nitrogen atoms respectively, 358.1 and 359.5°) while
the nitrogen N4 has a pyramidal configuration (sum of angles around N4 )
346.7°). This is likely to be a consequence of the location of N4 at a bridgehead
position between the two five-membered rings.
(17) Bock, H.; Schnoller, M. Angew. Chem. 1968, 7, 636. Bock and
Schnoller demonstrated using 15N-labeled azide that the R-nitrogen of the
original azide is the one present in the imine product, the â- and γ-nitrogen
atoms being evolved as molecular nitrogen.
(12) Quin, L. D.; Keglevich, G.; Caster, K. C. Phosphorus Sulfur 1987,
31, 133.
(13) (a) Abel, E. W.; Muckle, J. Inorg. Chim. Acta 1979, 37, 107. (b)
Imhoff, P.; Elsevier, C. J.; Stam, C. H. Inorg. Chim. Acta 1990, 175, 209. (c)
Reed, R. W.; Santasierso, B.; Cavell, R. G. Inorg. Chem. 1996, 35, 4292. (d)
Apppel, R.; Volz, P. Z. Anorg. Allg. Chem. 1975, 413, 45. (e) Crociani, L.;
Tisato, F.; Refosco, F.; Bandoli, G.; Corain, B.; Venanzi, L. M. J. Am. Chem.
Soc. 1998, 120, 2973.
(14) Reetz, M. T.; Bohres, E.; Goddard, R. Chem. Commun. 1998, 935.
(15) (a) Brunel, J. M.; Chiodi, O.; Faure, B.; Fotiadu, F.; Buono, G. J.
Organomet. Chem. 1997, 529, 285. (b) Legrand, O.; Brunel, J. M.; Constan-
tieux, T.; Buono, G. Chem.sEur. J. 1998, 4, 1061.
(18) (a) Westheimer, F. Acc. Chem. Res. 1968, 1, 70. (b) Mislow, K. Acc.
Chem. Res. 1970, 3, 321. (c) Luckenbach, R. Dynamic Stereochemistry of
Pentacoordinated Phosphorus and Related Elements; Georg Thieme Verlag:
Stuttgart, 1973; pp 99-107.
10.1021/ja984295g CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/05/1999

5808 J. Am. Chem. Soc., Vol. 121, No. 24, 1999
Communications to the Editor
Table 1. Catalytic Asymmetric Cyclopropanation of Olefins 8 by
Ethyl Diazoacetate 9
yield
ratio
ee (%)
entry L*
1a,i 6ac,d Ph
R
solvent
THF
(%)g 10:11h 10:11
68
61
67
60
80
85
78
83
78
89
76
71
78
95
5
92
8
80
20
76
24
98
2
95
5
97
3
95
5
82
18
90
10
100
0
98
2
83
17
17
0
2a,i 6ac,e Ph
3a,i 6ae,f Ph
4a,i 6ad,f Ph
5a,i 6ae,f Ph
6a,i 6ae,f Ph
7a,i 6ae,f Ph
8a,i 6be,f Ph
THF
34
12
52
43
63
20
94
90
93
91
92
91
87
76
84
76
50
35
95
THF
CH2Cl2
CH2Cl2
ClCH2CH2Cl
CHCl3
Figure 1. Structure of anti-6a, showing labeling scheme. Selected bond
distances (Å): P1-N2, 1.544(3); P1-N3, 1.686(3); P1-N4, 1.655(3);
P1-N5, 1.633(3); N2-C15, 1.406(4) N3-C7, 1.409(5). Selected bond
angles (deg): N2-P1-N3, 122.2(2); N2-P1-N4, 117.7(2); N2-P1-
N5, 106.0(2); N4-P1-N3, 92.8(2); N4-P1-N5, 109.9(2); N3-P1-
N5, 107.4(2); P1-N2-C15, 126.1(3); P1-N3-C7, 125.4(3); P1-N5-
C13, 119.4(3); P1-N4-C8, 114.9(3); P1-N3-C6, 113.6(3); P1-N5-
C17, 124.1(3); P1-N4-C16, 122.1(3); C6-N3-C7, 119.1(2); C8-N4-
C16, 109.7(3); C13-N5-C17, 116.0(3).
CH2Cl2
CH2Cl2
9a,i 3e,f
Ph
10a,i 6ae,f 1-Naphthyl CH2Cl2
11b,i 6ae,f 1-Naphthyl CH2Cl2
a favored apical position, allowing apical departure of molecular
nitrogen.20
12b,j 6ae,f PhCH2-
13b,j 6ae,f PhOCH2-
CH2Cl2
CH2Cl2
12
0
34
23
The catalytic asymmetric cyclopropanation of olefins with
various diazoacetates in the presence of chiral copper and rhodium
catalysts has been carefully optimized.21 The methods developed
by Evans,22a Pfaltz,22b Musamune,22c and Doyle22d are exemplify-
ing. Although these chiral catalysts can provide substituted
cyclopropanes with a high level of enantioselectivity, these
reactions are not highly diastereoselective, and a mixture of trans
and cis adducts 10 and 11 is obtained.23 Due to their metal
complexation properties,13 iminophosphoranes 3, 6a, and 6b have
been successfully used as ligands in an asymmetric copper-
catalyzed cyclopropanation of olefins 8 by ethyl diazoacetate 9
(see Table 1). The best results were obtained with copper(I)
triflate.24,25
a Reactions performed on 1 mmol scale at -20 °C during 72 h.
b Reactions performed on 1 mmol scale at -78 °C during 72 h.
c Reaction performed using 1 equiv of L* with respect to CuOTf.
d Rapid addition of N2CH2COOEt in 1 min. e Addition of N2CH2COOEt
using a pump syringe over a period of 10 h. f Reaction performed using
2 equiv of L* with respect to CuOTf. g Isolated yield. h Ratio 10:11
determined by capillary GC. i ee determined by HPLC analysis. j ee
determined by GC analysis using a LIPODEX E column.
stable trans isomer 10 which was preferentially formed (the trans/
cis ratio varying from 76/24 to 100/0 depending on the experi-
mental conditions and the nature of the considered olefin). Using
styrene as substrate test, dichloromethane appeared to be the best
solvent with respect to enantiomeric excesses (ee) and diastereo-
selectivity (entries 5, 94 and 90% ee, respectively, for trans-10
and cis-11 isomers (ratio 98/2)) while THF led to poor enanti-
oselectivities (entry 3, 52 and 43% ee, respectively for trans-10
and cis-11 isomers (ratio 80/20)). Furthermore, it clearly appears
that the rate of addition of ethyl diazoacetate is important to ensure
a high enantiomeric excess reproducibility (entries 4 and 5). Under
the best experimental conditions (entry 5), the use of iminophos-
phoranes 6b and 3 led to similar results in terms of conversion
and enantioselectivities (entries 8 and 9).26 Performing the reaction
on various olefins led in all cases to high ratio diastereoselec-
tivities varying from 83/17 to 100/0 (entries 10-13). The best
result was obtained using 1-vinylnaphthalene which led to a total
diastereoselectivity in trans-10 with 95% ee (entry 11). On the
other hand, when R ) PhCH2 and PhOCH2, we noticed a
significant decrease of the enantioselectivity (entries 12 and 13).
Additional studies dealing with the use of such ligands in
various asymmetric catalyzed reactions as well as mechanistic
features are under current investigations.
The expected adducts 10 and 11 were formed in chemical yields
varying from 60 to 85% using 1.5 mol % of the complex 6a-
CuOTf. In the case of vinyl aryl substrates, the catalyst exhibits
high enantiocontrol especially for the thermodynamically more
(19) Berry, R. S. J. Chem. Phys. 1960, 32, 933. Nevertheless, in any case
Turnstile rotation must be taken into consideration as a mechanistic alternative:
(a) Gillepsie, P.; Hoffmann, P.; Klusacek, H.; Marquading, D.; Pfohl, S.;
Ramirez, F.; Tsolis, E. A.; Ugi, I. Angew. Chem., Int. Ed. Engl. 1971, 83,
691. (b) Ramirez, F. Bull. Soc. Chim. Fr. 1970, 3491.
(20) The inversion of configuration at the phosphorus atom is energetically
unfavored since it would involve the epimerization of the phosphorus P(V)
atom implying high-energy intermediates in which the two rings will be forced
to adopt a constrained diequatorial position.18
(21) For recent reviews dealing with copper cyclopropanation reaction,
see: (a) Singh, V. K.; DattaGupta, A.; Sekar, G. Synthesis 1997, 137. (b)
Doyle, M. P.; Protopopova, M. N. Tetrahedron 1998, 54, 7919. (c) Doyle,
M. P.; Forbes, D. C. Chem. ReV. 1998, 98, 911.
(22) (a) Evans, D. A.; Woerpel, K. A.; Hinnan, M. M.; Feud, M. M. J.
Am. Chem. Soc. 1991, 113, 726. (b) Pfaltz, A. Acc. Chem. Res. 1993, 26,
339. (c) Lowenthal, R. E.; Abiko, A.; Masamune, S. Tetrahedron Lett. 1990,
31, 6005. (d) Doyle, M. P.; Dratkin, A. B.; Protopopova, M. N.; Yang, C. I.;
Miertschin, C. S.; Winchester, W. R.; Simonsen, S. H.; Lynch, V.; Chosh, R.
Recl. TraV. Chim. Pays-Bas 1995, 114, 163.
(23) For high trans diastereoselectivity of the reaction, see: Doyle, M. P.;
Bagheri, V.; Wandless, T. J.; Harn, N. K.; Brinker, D. A.; Eagle, C. T.; Loh,
K. L. J. Am. Chem. Soc. 1990, 112, 1906.
(24) Solomon, R. G.; Kochi, J. K. J. Am. Chem. Soc. 1973, 95, 3300.
(25) Copper(II) triflate complexes do not catalyze the reaction unless they
are heated to 65 °C. Other Cu(I) and Cu(II) salts (for example, halide, cyanide,
acetate, and perchlorate) show little or no catalytic activity, and the observed
enantioselectivity is markedly inferior to that obtained for the triflate-ligand
complexes.
Acknowledgment. We thank Dr. M. Giorgi for his kind assistance
with X-ray analysis of compound 6a. This paper is dedicated to Pr. H.
B. Kagan on the occasion of his 69th birthday.
Supporting Information Available: Experimental procedures for the
synthesis of phosphines 2, 5a,b and iminophosphoranes 3, 6a,b as well
as for catalytic asymmetric copper cyclopropanation reaction (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
(26) It is interesting to note that compounds 3, 6a, and 6b do not function
as imido donor groups for the aziridination of styrene catalyzed by CuOTf.
On the other hand, the corresponding ligands 2, 5a, 5b do not lead to the
formation with high level of enantioselectivity to the cyclopropane adducts
10 and 11 (enantioselectivity up to 7% ee).
JA984295G