J . Org. Chem. 1987,52, 5320-5325
5320
New Chiral Bicyclic Phosphoramides Derived from L-Glutamic Acid Jean-Frangois Peyronel Rhdne-Poulenc-SantB, Centre de Recherche5 de Vitry 13, Quai Jules Guesde, 94400 Vitry, France
Odile Samuel and Jean-Claude Fiaud* Laboratoire de Synthese AsymBtrique, U A 255,Bdt. 420, Universite Paris-Sud, 91405 Orsay Cedex, France Received March 13, 1987
New cyclic chiral phosphoramidea derived from (7aS)-1,2,5,6,7,7a-hexahydropyrrolo[ 1,2-~]diazaphosphole %oxide have been synthesized and isolated in 100%diastereomeric purity from (+)-(S)-glutamicacid. The configuration at the phosphorus atom and the diastereomeric purities have been determined for each compound through ‘H and 31PNMR examination. The enantiomeric purity for two compounds could be evaluated through the as measurement of 31PNMR shifts induced by addition of (-)-(R)-N-(3,5-dinitrobenzoyl)-l-phenylethylamine a chiral solvating agent. Hexamethylphosphoramide (HMPA) is often used to induce variations in the reactivity of transition-metal complexes. As an example, in the alkylation of palladium-complexed olefins, the use of HMPA could extent the scope of reagents from stabilized carbanions to ketone and ester enolates, oxazoline anions, and protected cyanohydrin anions.’ Moreover, in the alkylation of a-allylpalladium chloride by ester enolates, addition of HMPA led to a cyclopropanation reaction instead of an allylic alkylation.2 Few crystalline HMPA-containing transition-metal complexes have been described. Among them, Mo05HMPA3has been used for the epoxidation of olefins4 or allylic alcohol^.^ Mo05HMPA,pyridine (MoOPH) is a useful reagent for the oxidation of enolates of ketones, esters, and lactones into a-hydroxy derivatives6 and of cyanides into cyanohydrin^.^ Chiral analogues of HMPA are unusual. To the best of our knowledge, 1,* 28: and 2b1° were the only chiral phosphoramides yet to be described. Only one asymmetric synthesis has been reported to involve an optically active phosphoramide as ligand in complexes: the asymmetric epoxidation of trans-Zoctene by Moo5-pyridine-2b complexes.’O
Scheme I
u
IY
\R2
3
/i \C I
R1
0
-y /lo I
7
R2 8
/
P(0)CIS
! ‘ W
N
H
P
h
H
,NHR’
O=P-NHR~
0 1
N‘
HR2
20: R‘ = R~ = (is,2
~~~)-2-isopropy1, 5-methylcyclohexyl b: R’ = (R)-1-phenylethyl: R 2 = Me
We anticipated that structurally rigid chiral cyclic phosphoramides would be promising for ligand-induced asymmetric synthesis. No cyclic chiral phosphoramide has (1)Hegedus, L.S.;Williams, R. E.; McGuire, M. A.; Hayashi, T. J . Am. Chem. SOC.1980,102,4973. (2)Heaedue, L. S.;Darlinaton, W. H.; Russel, C. E. J. Om. Chem. 1980,45,b193. (3)Mimoun, H.; SCrCe de Roch, I.; Sajue, L. Bull. Soc. Chim. Fr. 1969, 1481. (4)Mimoun, H.; SCrC de Roch, I.; Sajue, L. Tetrahedron 1970,26,37. Arakawa, H.; Moro-Oka, Y.;Ozaki, A. Bull. Chem. Soc. Jpn. 1974,47, 2958. Arzoumanian, H.; Blanc, A.; Hartig, U.; Metzger, J. Tetrahedron Lett. 1974,1011. ( 5 ) Achrem, A.; Timotschtachuk, A.; Metelitza, D. I. Tetrahedron 1974,30,3165. Arcoria, A.; Ballistreri, F. P.; Tomaselli, G. A.; Di Furia, F.; Modena, G. J. Org. Chem. 1986,51,2374and references cited therein. (6)Vedejs, E.; Engler, D. A.; Telschow, J. E. J. Org. Chem. 1978,43, 188. (7)Vedejs, E.;Telschow, J. E. J . Org. Chem. 1976,41, 740. (8)Wilson, S. R.; Price, M. F. Synth. Commun. 1982,12, 657. (9)Kagan, H. B., personal communication. Tchang, S. Thesis, Orsay, 1982. .~ (10)Bortolini, 0.; Di Furia, F.; Modena, G.; Schionato, A. J. Mol. Catal. 1986,35, 47. ~
8b
8f
a: R’ = R2 = CH3 b: R’ = H: R 2 = CH3
c:R‘, R 2 =
P o W
d: R’, R 2 = ~ N - C H J
and 8g
9 : R’=CH3: R 2 = C H 2 C 0 2 E t h : R’=CH3: R 2 = C(S)NHCH3
i : R’. R ~ c)=NH: =
-CN
j : R = C H 3 : R’: H : R 2 = COCzH5 ~ : R = H : R ’ = R ~ = C ~ H ~
e: R’ = H: R 2 = (CH2)2N(CH3)2 f : R’ = CH3: R2 = C H 2 C r C H
been reported so far. In this paper are presented details of the preparation, separation, and structural assignments of the 3R and 35’ isomers of some (7aS)-1,2,5,6,7,7ahexahydropyrrolo[1,2-c]diazaphosphole 3-oxides 3. We aimed a t devising a versatile synthetic scheme to prepare phosphoramides 3 with variations for R1,R2,and R3 and configurations at P-3 and C-7a. Synthetic Procedures for the Preparation of 3 and 8. The syntheses were carried out in a one-step procedure (Scheme I, path A) by treatment of chiral diamines 4 with
0022-3263/87/1952-5320$01.50/00 1987 American Chemical Society
J. Org. Chem., Vol. 52, No. 24, 1987 5321
New Chiral Bicyclic Phosphoramides Scheme I1
Table 11. 'HNMR Data for Compound 8
d,,,H C02H
( 1 ) SOC12/EtOH
H02C
a
Et0 0
NH2 ( 2 ) N H 4 0 H
-
H
H
'RNH2
NH2
(96%)
0
I
H
CONHR
L A H . THF.
A NHR
I
A
4
Table I. PreDaration and Physical Data for 3 and 8 config at synth compd Pa route yield, % b mp, "C [cY]D,~deg 25 100 -25.5 A,B 8a S A 33 150 +86 8a R 35 120 -26 A 3 8b S A 24 191 +79.8 8b R 27 98 -41 8c S A A 18 152 +84 8c R -38.8 A 13 108-110 8d S A 13 164 +85 8d R 8e S B 61 150 -3d C 55 140 8f S C 56 112 +72 8f R 90 -13 8g S C 40 C 50 92 +80 813 R C 48 150 -3.8 8h S -52.2 8i S C 50 A 16 202 -89 3j S oil 3j R,S A 36 210-211 +34d 3k R A 9.4 190-191 3k RS A 22
~~
comDd 8a Sa 8b 8b 8c 8c 8d 8d
confie at P S
843
S S
8f 8f 8h 8h 8i
R S
R S
R S
R
R S
R S
H'-1 3.21 3.26 3.23 3.40 3.25 3.5 3.28 3.3 3.28 3.3 3.33 3.55 3.54 3.5
chemical shifts: H-1 H'-5 3.76 2.81 3.13 3.68 2.80 3.85 3.67 2.93 3.01 3.79 3.74 3.15 3.78 2.83 3.1 3.67 3.82 2.78 3.8 2.83 3.72 2.95 2.97 4 3.94 2.90 4.23 3
ppm H-5 H-7a 3.47 3.76 3.87 2.94 3.49 3.65 3.40 3.84 3.79 3.55 3.4 3.98 3.41 3.78 3.17 3.91 3.50 3.82 3.47 3.98 3.21 3.91 3.55 4 3.15 4.08 3.15 4.23
In DMSO, relative to TMS.
ration through silica gel column chromatography (Table I). Structural and Stereochemical Assignments. Structural and stereochemical assignments were made on rationalization of the 'H and 31P(1H]NMR data, assuming "Attributed on the basis of 'H and 31PNMFt chemical shifts (see that the bicyclo[3.3.0] ring system with bridgehead nitext). bIsolated yield (not optimized). cAcetone, c 1. dCHC13,c 1. trogen should show a low-energy cis-fused ~onfiguration.'~ For all compounds 8 described in the table, the 3 s conthe appropriate phosphoramidic dichlorides 5. Although figuration a t phosphorus atoms corresponds to an endo derived from proline," diamines 4 were more readily and P=O configuration. Conversely the compound 7 with economically obtained from glutamic acid (commercially endo P=O configuration has a R configuration a t the P available in both enantiomeric forms) as outlined in atom, as a consequence of the modification of the order Scheme 11. 6 (4, R = Ph) was prepared in a two-step of priority of the substituents. procedure from (S)-(+)-glutamic acid according to Iriu(1) 'H NMR Data. The absolute configuration at chuima. l2 phosphorus in diastereomeric 7 and 8 was assigned through Through a second procedure (Scheme I, path B), the examination of the 'H NMR data and comparison of the diamine 6 reacted with phosphoryl chloride (POC13)to give lanthanide-induced shifts. the diastereomeric 3-chloro-1,2,5,6,7,7a-hexahydro-2In phosphorus-containing heterocycles, protons in a phenylpyrrolo[l,2-c] [1,3,2]diazaphosphole 3-oxide (7; in 1,3-cis relation to a P=O group are de~hie1ded.l~Coma 93:7 ratio after liquid chromatography). Samples of pure parison of the chemical shifts for the H-1 and H-5 protons diastereomers could be isolated by column chromatograwithin the pair of diastereomers 8 showed a through-space phy. To the major diastereomer was assigned the 3 s deshielding effect A6 0.2-0.5 of P=O a t the H-5 and H-1 configuration by 'H NMR examination (vide infra). I t protons for (3S)-8 relative to (3R)-8 (Table 11). H-7a gave with NH2(CH2)2NMe2 a single diastereomer 8e (isoprotons were deshielded in (3R)-8 (A6 0.1-0.2) relative to lated as the oxalate salt) to which the 3 s configuration was (3S)-8, probably owing to the same effect. Moreover, in assigned ('H and 31PNMR): the substitution thus prothe 3R series, H-7a was generally found as the most deceeded with inversion of configuration a t the P atom. shielded aliphatic proton. In the third procedure (Scheme I, path C), 8b, prepared The same trends were observed for compounds 7 (for by reaction of 6 with the appropriate N-methylwhich the diastereomer with endo P=O has a 3R configphosphoramidic dichloride (5b), was N-alkylated after uration). Absolute configuration a t the phosphorus atom deprotonation (BuLi) to give the phosphoramides 8f,g. for 7 could be confirmed by lanthanide shift experiments. Use of n-BuLi as a base for deprotonation proved to be The phosphoryl oxygen in 1,3,2-oxazaphospholidine2superior to NaH13 which gave degradation products oxide structure is the most likely to coordinate preferenthrough the opening of the 1,3,2-diazaphosphole ring. tially with lanthanide shift reagents.16 Small amounts of In most cases, the phosphoramides 3 (epimeric a t the phosphorus atom) were obtained in a pure (98%) diaste(14) Crabb, T. A.; Newton, R. F.;Jackson, D. Chem. Rev. 1971,71,109. reomeric form either by repeated crystallization or sepaKoizumi, T.; Yamada, R.; Takagi, H.; Hirai, H.; Yoshii, E. Tetrahedron (11) Asami, M.; Ohno, H.; Kobayashi, S.;Mukaiyama, T. Bull. Chem. SOC.Jpn. 1978, 51, 1869. Mukaiyama, T. Tetrahedron 1981, 37, 4111. (12) Iriuchuima, S. Synthesis 1978, 684. (13) Corbel, B.; Paugam, J. P.; Sturtz, G. Can. J . Chem. 1980,58,2183.
Lett. 1981,22, 477. (15) Quin, L. D. The Heterocyclic Chemistry of Phosphorus; WileyInterscience: New York, 1981; p 349. Maryanoff, B. E.; Hutchins, R. 0. J. Org. Chem. 1977,42,1022. Chen, K. C.; Ealick, S. E.; Vander Helm, D.; Barycki, J.; Berlin, K. D. J. Org. Chem. 1977, 42, 1170. Mile, J. A.; Grabiak, R. C.; Navech, J.; Mathis, F. Org. Magn. Reson. 1976, 8, 399.
5322 J. Org. Chem., Vol. 52, No. 24, 1987
~
H-5
-
7
~ H-I
Peyronel et al.
nw
NO2 ( R )-9
6(wmJ 5
3
Figure 1. 'H NMR data for LIS experiments on (3R,7&)-7 and (3S,7aS)-7. Table 111. compd 8a 8b 812 8d 8ec 8f 8g
8h 3j
3k
NMR Spectral Data" for 8 and 3 exo P=O (3sconfig at P) 18.9 25.3
endo P=O (3R config at P) 18.42b 17.7 15.2 16.2
24.98* 24.6 22.85 22.5 23.6d 24.1 23.57b 24.6 23.3d 24.6
17.5 17.68b 17.0 19.7
"In DMSO-&; ppm downfield from 85% H3P04,the external reference. bCDC13as solvent. e With 1.5(COzH)z (as the sesquioxalate). Only one diastereomer was isolated. The 3s configuration was assigned on the basis of the 31Pvalue. E ~ ( f o d were ) ~ added to CDC1, solutions of (3R)- and (3S)-7, and the lH NMR spectra were recorded after each addition. Graphs were plotted for each proton against the proportion (w/w) of shift reagent (Figure 1). Since it is expected that proton in a cis relation to the P=O group coordinating the shift reagent will exhibit a smaller slope than those in a trans relation, the H-5 with 6 3.85 was assigned to the 3R isomer (endo P=O), in agreement with the previous attribution (vide supra). Such a trend was not observed in LIS experiments with the diastereomeric amides 8a. The most rapidly shifted protons were those of the NMez group in each isomer, indicating a preferential coordination of the europium complex with this group, relative to the P=O group. NMR Data. Diastereomeric and Enantiom(2) eric Purities. Differences of about 6-7 ppm were recorded for the NMR shift of each diastereomer in 8a-h (Table 111). This constitutes a good criteria for evaluation of the diastereomeric purities of phosphoramides. Diastereomers of the exo P=O series showed higher 6 values (23 ppm) than those of the P=O endo series (
