Thermally induced and transition metal catalyzed aza-Claisen rearrangement of 2-cyclopropylideneethyl imidates: A new entry to 1-aminocyclopropanecarboxylic acids

Tetrahedron Letters.Vol.36, No. 17, pp. 2975-2978, 1995 ElsevierScienceLtd Printedin GreatBritain 0040-4039/95 $9.50+0.00

Pergamon 0040-4039(95)00380-0

Thermally Induced and Transition Metal Catalyzed Aza-Claisen Rearrangement of 2-Cyclopropylideneethyl Imidates : A New Entry to 1-Aminocyclopropanecarboxylic Acids. Karine Estieu, Jean Ollivier and Jacques Sala/in* Laboratoire des Carbocycles (Associd au CNRS), Institut de Chimie Mol~culaire d'Orsay, Bat. 420, Universit6 de Paris-Sud, 91405 Orsay (France)

Abstract: (2-Cyclopropylideneethyl)acetimidates underwent thermally induced or palladium (II) catalyzedaza-Claisenrearrangementinto 1-ethenylcyclopropylacetamides,providingconvenientprecursors to 1-amino cyclopropanecarboxylicacids (ACCs). Due to the regioselectivity of the nucleophilic substitutionof the ~ 1,l-dimethyleneallyl palladiumcomplexesby soft nucleophiles,the palladium(0) catalysiswas apparentlynon effective. Functionalized cyclopropanes, specially 1-vinylcyclopropanol derivatives, provide building blocks of unprecedented synthetic potential.l Naturally occurring or non-natural cyclopropane-containing compounds, bearing simple functionalities, are endowed with a large spectrum of important biological properties.2 Among them, 1-amino-l-cyclopropanecarboxylic acids (ACCs) attract special attention due to their phytochemical, enzymatic, antibiotic and neurochemical activities.2,3 Several methodologies have been recently developed for the synthesis of this peculiar class of strained amino acids.4 We have previously reported that the direct amination of cyclopropanecarboxylic acid and methyl ester enolates or that the nucleophilic substitution of 1-aminocyclopropanols by cyanide anion failed to provide a convenient entry to ACCs.5-7 On the other hand, nucleophilic substitutions with retention of the threemembered ring were rather difficult and rare 8 but, we have recently shown that 1-ethenylcyclopropyl esters underwent regioselective palladium (0) catalyzed substitution reactions by stabilized (soft) and non-delocalized (hard) carbon nucleophiles, without ring opening.9 Unfortunately, palladium (0) catalyzed attempted amination of these 1,1-dimethyleneallylic esters by amines, imines, hydroxylamines, carbamates occurred exclusively on the less substituted allylic end, providing 2-cyclopropylideneethylamine derivatives ; only palladium (0) catalyzed azidation by sodium azide led unexpectedly to 1-azido- l-ethenylcyclopropanes.10

CI3CCN " CH2OH

10% Nail

~ C H 2I HN ~

A

O

,

[ ~

---~ . NHCOCCI3

~>~COOH NH2

/

1

2 (93%) CCI3

3 (96%)

4 (87%)

We have investigated the aza-Claisen rearrangement of the trichloroacetimidate 2, in order to provide a new route to ACCs. Thus, addition of trichloroacetonitrile (1.5 equiv.) to the cyclopropylideneethanoi 1, 9,11 readily available from the cyclopropanone hemiacetal, 12 in the presence of 10% of sodium hydride, gave the imidate 2 14 in 93% yield. On heating in toluene at 100°C for 48 h or at 110°C for 36 h, the amide enolate 2 underwent the thermal [3,31 sigmatropic rearrangement known as aza-Claisen rearrangement, 15 to provide the 1-

2975

2976

ethenylcyclopropyl trichloroacetamide 3 in 96% yield. 14,16 Oxidation of 3 [NalO4 (4 mol.equiv.), RuCI3 (cat.), C C I 4 / C H 3 C N / H 2 0 ,

ratio 2/2/3] at room temperature, furnished the corresponding

cyclopropanecarboxylicacid without affecting the trichloroacetamide moiety. Finally, treatment with 3M HCI at reflux for 4 h and ion-exchange (Dowex 50 WX 8.100) chromatography gave the ACC-4 in 87% overall yield from 3. As the thermal rearrangement of allylic imidates has been shown to take place with little diastereoselection 17, we have then investigated this aza-Claisen rearrangement under catalytic conditions, in order to provide by this way a diastereoselective synthesis of substituted ACCs. 18 Although mercury (II) salts have been successfully used to catalyze the Claisen rearrangement of some allylic trichloroacetimidates,15 treatment of 2 with mercuric trifluoroacetate in methanol or benzene at room temperature led surprisingly, to the anti-Claisen product 5.14, 19 Hg(CF3~) 2 2

H •

~N/%CCI3 anti-Claisen - 5

0

Treatment of 2 with nickel (II) catalyst [NiCl(dppe)2], required heating at 100°C, so this catalyst was not effective. On the other hand, treatment of 2 with 5% of palladium (0) (from Pd(dba)2 and 2 PPh3 or dppe) at 20°C and on heating at 50°C (decomposition was observed at 80°C), gives neither the expected Claisen product 3 nor the anti-Claisen 5; apparently, the allylic imidate 2 which was recovered unaltered, was inert to palladium (0) catalysis. 20 In fact, the g 1,1-dimethyleneallyl palladium (0) complex 6 9 and the trichloroacetamide anion 7 were likely formed but, as previously shown, this anion 7 has the behaviour of a soft nucleophile, i.e. its reacted on the primary vinylic end of 6, exclusively 10, leading reversibly to the imidate 2. As none anti-Claisen product 5 was formed, this suggested that on the anion 7, the oxygen was more nucleophilic than the nitrogen.

(COOMe 2

Pd(0)

•

/

6

"~

Nil. ( ~ . O

COOMe

~,-

Nail 8 0O0%)

I

CCI3 7 However, treatment of the imidate 2 by palladium (0) in the presence of 1.1 equiv, of malonic ester enolate (Nail, dimethyl malonate) in THF at room temperature for 18 h, gave quantitatively the dimethyl (2cyclopropylideneethyl)malonate g;9,14 while no reaction was observed in the absence of any palladium (0) catalyst. Indeed, these results suggested the occurrence of 6. Otherwise, treatment of 2 with palladium (II) catalyst [PdCI2(CH3CN)2 or PdCI2(PhCN)2] in benzene at room temperature for 40 h gave the coordinated methylenecyclopropane 9, which underwent intramolecular attack by the lone pair of the imidate nitrogen atom to produce the metal bound six-membered cyclic carbonium ion intermediate 10.19 Its rearrangement led to 3 and regenerated the catalyst, but the only formed product in 72% yield,21 was the N-(2-cyclopropylideneethyl)N-(1-ethenylcyclopropyl)trichloroacetamide11,14 resulting likely from the electrophilic attack of 3 by the palladium (0) complex 6, arising either from 10 or directly from 2. (For a similar double N-alkylation of benzylamine by 6, see ref. 10).

2977

2

=

~

~

9

CCI3

~.

10

6

3

~

CCI3

N"coccI3

I1 (72%)

In order to avoid the subsequent reaction 3 ~ 11, many attempts to protect the nitrogen atom of imidate 2 have been performed. Thus, reactions of the sodium (lithium or potassium) salt of 2, prepared by reaction of the allylic alcohol 1 with Ci3CCN in the presence of one equiv, of Nail (MeLi, t-BuLi, KH or t-BuOK), with tdmethyl- and t-butyldimethylchlorosilanes,di-t-butyldicarbonate (BOC)20 or benzyl chloride, respectively, have failed under various conditions. Likewise, reactions of the imidate 2 with benzylamine hydrochloride

(transimination reaction), chlorosilanes in the presence of NEt3, (BOC)20 in the presence of NEt3 and DMAP or Na2CO3 did not provided any N-protected imidate derivatives. ~ C H

2

I

RN~,,, O

A or PdCI2(PhCN)2

-

D("

Ph 12a R=Ph b CH2Ph c p-C6H4OMe

NRCOPh 13 a-e

Then, the sodium salt of I (one equiv, of Nail) was reacted with N-phenylbenzimidoylchloride 19,22 to produce the N-phenylbenzimidate 12a (R = Ph). 14, 23 Upon heating in xylene at 140°C for 124 h, or in the presence of palladium (II) catalyst in benzene at 50°C for 42 h, 12a underwent the aza-Claisen rearrangement to provide the N-benzoyl-N-phenyl-l-ethenylcyclopropylamine13a in 55 and 76 % yields after chromatography, respectively. In the same way, reaction of 1 with N-benzylbenzimidoylchloride24 either in the presence of one equiv, of Nail or of NEt3-DMAP, led to the N-benzylbenzimidate 12b (R = CH2Ph). 14, 23 Upon heating in xylene at 140°C for 133 h, 12b was rearranged into the N-benzoyl-N-benzyl-l-ethenylcyclopropylamine13b 14 in 18 % yield, after chromatography. At lower temperature, i.e., in toluene at 110°C, 12b was not rearranged, but underwent decomposition into N-benzyl benzamide at higher temperature or under FVT at 600°C; formation of unidentified products was observed in the presence of palladium (II) catalyst. Reaction of 1 with Nail (one equiv.) and N-p-anisylbenzimidoyl chloride led to the N-panisylbenzimidate 12c (R = p.C6H4OMe) 14, 23 which underwent, thermally induced on heating in xylene at 140°C for 44 h and palladium (II) catalyzed at 60°C for 12 h, aza-Claisen rearrangement to provide the N-panisyl-N-benzoyl-l-ethenylcyclopropylamine13c 14 in 60 and 74% yields after chromatography, respectively. Deprotection of the amine function by cleavage of the N-p-anisyl bond by treatment with ceric (IV) ammonium nitrate (CAN) 25 did not lead to the benzoyl equivalent of 3, but to a 2-vinyl azetidine derivative from ring enlargement. 1 References

1.

and

Notes

For reviews see : (a) Salaiin,J. Rearrangementsinvolvingthe cyclopropylgroup. In The Chemistry of the Cyclopropyl

Group ; Rappoport, Z., Ed.; Wiley:New York, 1987 ; p. 809-878 ; (b) Salaiin,J. Synthesisand SyntheticApplicationsof

2978

l-Donor Substituted Cyclopropanes with Ethynyl, Vinyl and Carbonyl Groups. In Small Ring Compounds in Organic

Synthesis ; de Meijere, A., Ed.; Topics in Current Chemistry ; Springer: Berlin, 1988 ; Vol. 144, p. 1-71. 2.

For a review see : Salaiin, J.; Baird, M.S. Biologically Active Cyclopropanes and Cyclopropenes. Curr. Med. Chem. 1995, 2, 545-575..

3.

For reviews see : (a) Wagner, I.; Musso, H. Angew. Chem. Int. Ed. Engl., 1983, 22,816 ; Co) Stammer, C.H. Tetrahedron 1990, 46, 2231 ; (c) Alami, A.; Calmes, Daunis, J.; M.; Jacquier, R. Bull. Soc. Chim. Fr. 1993, 130, 5.

4.

For a review see : Burgess, K.; Ho, K.K.; Moye-Sherman, D. Synlett 1993, 575 ; Alcaraz, C.; Fernandez, K.D.; de Frutos, M.P.; Marco, J.L.; Barnabt, M.; Foces-Foces, C.; Cano, F.H. Tetrahedron 1994, 50, 12443 and references cited therein.

5.

Salailn, J.; Marguerite, J.; Karkour, B. J. Org. Chem. 1990, 55, 4276.

6.

For the nitration of a sterically hindered cyclopropanecarboxylate, followed by reduction into ACC, see Haner, R.; Seebach,

D. Chimia 1985, 39, 356. 7.

For the one-pot Strecker reaction of a cyclopropanone acetal under sonication, see : Fadel, A. Tetrahedron 1991, 47, 6265.

8.

Howell, B.A.; Jewett, J.G.J. Am. Chem. Soc. 1971, 93,798 ; Salafin, J. J. Org. Chem. 1976, 41, 1237 ; 1977, 42, 28 ; 1978,43, 2809 ; Banert, K. Chem. Ber. 1985, 118, 1564.

9.

Stolle, A.; Ollivier, J.; Piras, P.P.; Salaiin, J.; de Meijere, A. J. Am. Chem. Soc. 1992, 114, 4051.

10.

Aufranc, P.; Ollivier, J.; Stolle, A.; Brener, C.; Es-Sayed, M.; de Meijere, A.; Salatin, J. Tetrahedron Left. 1993, 34, 4193.

11.

Cyclopropylidenethanol

1 was obtained in 89% yield from the benzoic acid catalyzed Wittig reaction of l-

ethoxycyclopropano112 with ethoxycarbonylmethylenetriphenylphosphorane,13 followed by diisobutylaluminium hydride reduction. 9 12.

Salaiin, J.; Marguerite, J. Org. Synth. 1984, 63, 147.

13.

Spitzner, D.; Swobada, H. Tetrahedron Lett. 1986, 27, 1281.

14.

All compounds gave satisfactory spectra and analytical data.

15.

Overman, L.E.J. Am. Chem. Soc., 1974, 96,597 ; 1976, 98, 2902 ; Clizbe, L.A.; Overman, L.E. Org. Synth. 1978,

58, 4 ; Overman, L.E. Angew. Chem. Int. Ed. Engl. 1984, 23, 579. 16.

At higher temperature, i.e., on heating in xylene at reflux (140°C), 2 underwent degradation ; but 3 was obtained in 60 and 80% yields on microwave irradiation at 130 and 140°C, for 10 mn, respectively. On heating neat 2 at 120°C for 2 h 30, 3 was obtained in 26% yield, but underwent degradation at 130°C. Use of polar solvent, i.e., acetonitrile or ethanol at 80°C gave 0 and 15% of 3, respectively.

17. 18.

Gonda, J.; Helland, A.-C.; Ernst, B.; Bellus, D. Synthesis 1993, 729. For the total asymmetric syntheses of natural and non-natural norcoronamic and coronamic acids, see : Gaucher, A.; Ollivier, J.; SalaiJn, J. Synlett 1991, 151 ; Gaucher, A.; Ollivier, J.; Marguerite, J.; Paugam, R.; Salaiin, J. Can. J. Chem. 1994,

72, 1312. 19.

Schenck, T.G.; Bosnich, B. J. Am. Chem. Soc. 1985, 107, 2058.

20.

Ikariya, T.; Ishikawa, Y.; Hirai, K.; Yoshikawa, S. Chem. Lett. 1982, 1815.

21.

The yield of crude 11 was 72%; but in fact this labile compound was isolated in 35% yield after liquid chromatography.

22.

Lander, G.D.J. Chem. Soc., 1902, 591 ; Ugi, I.; Beck, F.; Fetzer, V. Chem. Ber. 1962, 95, 126.

23.

Crndes imidates 12a-c were formed quantitatively but, these labile compounds underwent partial decomposition on

24.

Pechmann, H.v.; Heinze, B. Chem. Ber., 1897, 30, 1788 ; Lander, G.D.J. Chem. Soc. 1903, 83, 320.

25.

Kronenthal, D.R.; Han, C.Y.; Taylor, M.K.J. Org. Chem. 1982, 47, 2765 ; Fukuyama, T.; Frank, R.K.; Jewell, C.F.J.

chromatography and were isolated pure in 50, 15, 20% yields, respectively.

Am. Chem. Soc. 1980, 102, 2122.

(Received in France 10 February 1995; accepted 27 February 1995)