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Methyltrioxorhenium(w)-Catalyzed Epoxidation of Alkenes with the Urea/Hydrogen Peroxide Adduct Waldemar Adam* and Catherine M. Mitchell

Selective catalytic oxidations are rapidly gaining impor- tance in organic synthesis. The use of transition metal complex- es as catalysts for such reactions is of particular interest,”] on the one hand because of the high selectivity and the versatility of these complexes and on the other hand due to their ability to activate oxidants such as molecular oxygen and hydrogen peroxide. During the last five years, a broad spectrum of transformations of organic compounds catalyzed by the organometallic complex methyltrioxorhenium (MTO) has been reported.I2] The epoxidation of olefins with hydrogen peroxide was the first type of reaction to be (Scheme 1). Although the oxidation of olefins in many cases

MTO

R O R rearrangement ‘fiR hydrolysis .- -

R HO‘R

3 Scheme 1.

i k i k 2 1

leads efficiently and selectively to the corresponding epoxides, a typical side reaction is the conversion of the hydrolytically sen- sitive epoxides to 1 ,2 -d io l~ , [~~] which sometimes undergo cleav- age and rearrangement reactions (pinacol rearrangement, Hock cleavage, etc.). Such secondary reactions can now be suppressed by replacing hydrogen peroxide with the urea/hydrogen perox- ide adduct (UHP) as primary oxidant. This enables epoxida- tions to be carried out in nonaqueous media, whereby the for- mation of diols and cleavage and rearrangement reactions are largely avoided. In the case of the epoxidation of chiral allylic alcohols, for the first time high diastereoselectivities (dr > 90:lO) were achieved for an MTO-catalyzed reaction.

H,O, adducts have already been widely employed as oxidants in organic synthesis13] and are also particularly important in the detergent industry; one example is the peroxy salt 4Na,SO,. NaCI.2 H,O, in neutral washing powder^.[^'.^] The only known metal-catalyzed oxidations are the epoxidation of 1,2-dihy- dronaphthalene with wealhydrogen peroxide catalyzed by a Mn(salen) derivative (H, salen = bis(salicy1iden)ethylenedi-

[*] Prof. Dr. W. Adam, Dip1.-Chem. C. M. Mitchell Institut fur Organische Chemie der Universitat Am Hubland. D-97074 Wiirzburg (Germany) Fax: Int. code +(931)888-4756 e-mail. adam((r chemie.uni-wuerzburg.de

[**I This work was supported by the Deutsche Forschungsgemeinschaft (SFB 347 “Selektive Reaktionen metallaktivierter Molekdle”), Schwerpunktprogramm “Peroxidchemie. Mechanistische und praparative Aspekte des Sauerstoff- transfers”. Bayerischer Forschungsverbund Katalyse (FORKAT), and the Fonds der Chemischen Industrie. We are grateful to Prof. Dr. W. A. Herrmann for a generous supply of methyltrioxorhenium.

amine)[51 and the Mn(porphyrin)-catalyzed epoxidation of cy- clooctene with various H,O, adducts.[6] The adducts used in these cases include Na,CO,, (CH,),NO, and (C,H,),PO, and also urea in one case. The urea presumably acts as a ligand; moreover, in the form of the adduct, which is present in solid and undissolved form, it also allows the H,O, concentration in the reaction mixture to be exactly dosed. However, in most cases the addition of a coreactant (acetic anhydride, maleic anhydride, para-nitrobenzoyl chloride, para-nitrobenzoyl imidazolide, phthalic anhydride, tetrabutylammonium hydroxide, trifluoro- acetic anhydride, etc.) is necessary for successful oxidation.

The use of additives such as amines, for instance 4,4- dimethyL2,2’-bipyridine, quinine, and quinchonine,[2b. ’dl has been reported for MTO-catalyzed epoxidations directly with hydrogen peroxide. Although formation of 1,2-diols is thereby suppressed, the activity of the catalyst is also diminished.[2d1 When an equimolar amount of the adduct (with respect to the oxidant) is used, the conversion drops by 23% for 2,2’- bipyridine, by 60% for quinoline, and even by 96% in the case of isoquinoline. In contrast, when UHP is employed as oxidant, the respective epoxide is obtained selectively, often with high conversion.

We report here on our investigation of the MTO-catalyzed epoxidation of several selected olefins. Our results (Table 1) show that the hydrolytic ring-opening of the epoxide 2 to give the corresponding diol3 with aqueous H,O, (Table 1, entries 2 and 5 ) can be avoided with UHP (Table 1, entries 1 and 4). As the most striking example, the reaction of camphene (Table 1, entries 4 and 5 ) in the absence of urea adduct and after only 3 h

Table 1 MTO-catalyzed epoxidation of olefins with the ured hydrogen peroxide adduct (UHP) [a]

Entry Olefin Oxidant f

1 [hl

1 cyclohexene UHP 18 2 cyclohexene H,O, ( 8 5 % ) 18 3 1-methylcyclohexene UHP 19 4 camphene UHP 30 5 camphene H,O, (85%) 3 6 styrene UHP 19

8 indene UHP 31

10 trans-stilbene UHP 19 11 trans-cinnamyl UHP 24

7 x-methylstyrene UHP 21

9 1,l-diphenylethene UHP 20

alcohol

Conv. [”/.I

98 71 88

27 46 81 51 81 44 66

92 [dl

Epoxide [b] 1.2-Diol [b, c] 2 3

99 1

96 4 2 95 0

2 95 0 68 32

2 9 5 0 93 I

2 95 0 2 9 5 [el 0

0 82(18)

0 0 ( 2 9 5 )

~

[a] 0lefin:oxidant:MTO = 1 : 1.0.01 (mol ratio) in CDCI,, ca. 20 “C. argon atmos- phere, mass balance loo%, error 1 5 % of the stated values. [b] Normalized to 100% conversion. [c] Yield of the pinacol rearrangement product (aldehyde) in parentheses. [d] Traces of rearrangement products were also obtained. [el Traces of trans-cinnamaldehyde were detected in the ‘H NMR spectrum ofthe crude reaction mixture

results exclusively in cleavage and rearrangement products; however, with UHP only the desired camphene oxide is ob- tained, which is stable under the modified reaction conditions (conversion 92% after 30 h at room temperature (ca. 20°C) with UHP in CDCI,). In the absence of MTO no reaction takes place under otherwise identical reaction conditions. Further ex- amples (Table 1, entries 3, 6, 8-11) illustrate the scope (< 10% ring opening); considerable hydrolysis (ca. 32 ”0) occurs only for the very hydrolytically sensitive sc-methylstyrene oxide (Table 1, entry 7). Presumably the high Lewis acidity of the peroxo complexes A and B (Scheme 1) is not sufficiently buffered by the addition of urea to suppress completely such secondary reactions under the reaction conditions. Related ad-

Aiigeh%. ChiJm. Inr. C I . Engl. 1996. 3s. N o . S C VCH &rlugsgesellsehufi mbH. 0-69451 Wemheim, 1996 OS7O-OR33lY6~3SOS-OS33 S iS.OO+ .25 0 533

ditives such as amides, peptides, and amino acids, which control the hydrolysis of cyclohexene oxide in analogy to urea (not shown in Table l ) , have a much more limited influence on the reaction. So far the mechanism behind the buffering effect of these additives on the Lewis acidity of ReV" has not been eluci- dated.

In the case of electron-poor olefins such as trans-cinnamalde- hyde, trans-methyl cinnamate, and 2-cyclohexenone (not shown in Table l), the reactivity of the substrate is reduced to such an extent that the epoxidation competes with the decomposition of the catalyst. Even after approximately 20 h at about 20 "C with UHP in CDCI, hardly any conversion (I 5 YO) was observed for these substrates.

To date, the diastereoselectivity of the MTO-catalyzed epoxi- dation has not been investigated, presumably because of the various subsequent reactions (hydrolysis, cleavage, rearrange- ment), which can now be avoided with UHP as oxidant. To test the selectivity, the epoxidation of chiral allylic alcohols la - f to give the respective threo- and erythro-epoxy alcohols 2 a-f was carried out, for which high yields (2 95 %) were achieved (Table 2). What is noticable in Table 2 are the high diastereose-

Table 2. MTO-catalyzed oxidation [a] of chiral allylic alcohols 1 to the correspon- ding rhreo- and erylhro-epoxides 2 with the urea/hydrogen peroxide adduct and comparison with the diastereoselectivities of reported epoxidations.

threoleryrhro Diastereoselectivity (dr) Entry Allylic alcohol I Conv. MTO/ mCPBA VO(acac),/

[h] [%] UHP lBuOOH

3

la

rj" l b

lc

5 2 5

Id

le

If

17

20

20

2s

15

17

88

83

90

2 95

91

88

50: 50

67:33

82:18

91.9

83117

95: 5

45:55 [b]

64:36 [b]

95:5 [b]

90: 10 [c]

95:5 [b]

90: 10 [d]

5:95 [b]

29:71 [b]

71:29 [b]

33:67 [c]

86:14 [b]

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534 0 VCH Verlags~esrllschafr mbH, 0-69451 Wemheim, 1996 OS70-0833/96/3505-0534 $ 15.00+ .25/0 Angew. Chem. Int. Ed. Engl. 1996, 35. No. 5

[a] Olefin.oxidant.MT0 =1:1:0.01 (mol ratio)inCDCl3,ca.2OoC,argonatmos- phere, mass balance loo%, error iS% of the stated values. [b] Ref. 191. [c] Ref. [lo]. [d] Ref. [ l l ] .

lectivities (threolerythro > 80:20) for substrates l c - f (Table 2, entries 3-6) in comparison with those for 1 a,b (Table 2, en- tries 1 and 2). It is mechanistically relevant to compare the derivatives 1 a (1,2-allylic strain), l c (1,3-allylic strain), and I d (1,2- and 1,3-allylic strain), as the diastereoselectivities in Table 2 (entries I , 3, and 4) show. The 1,3-allylic strain['] is decisive for the high diastereoselectivities demonstrated by re- sults obtained with substrates 1e,f (Table 2, entries 5 and 6); it operates in combination with the established hydroxyl group control['] to afford the preferred threo isomer. These high n-fa- cia1 diastereoselectivities point to pronounced interaction be- tween the oxygen acceptor (chiral allylic alcohol) and the acti- vated oxygen donor (diperoxorhenium complex) by the formation of hydrogen bonds.

To ascertain the structural aspects of the interaction between the chiral allylic alcohol substrate and the metal-activated oxidant, a comparison with stereochemically established epoxi- dations such as those with peracid (threo-sele~tive)[~ - "1 and VO(acac),/tBuOOH (erythr~-selective)[~. ''1 is informative (Table 2). In the epoxidation of the allylic alcohol 1 d (Table 2, entry 4) as a stereochemical probe (1,2- and 1,3-aIlylic strain), it becomes clear that the MTOjUHP reaction proceeds through a transition state analogous to the peracid transition state threo- Id" and not one analogous to erythro-id*, the VO(acac),/

Y R

rhreo-ld?

CH3

eryrhro-ld'

tBuOOH transition state. Therefore it is certain that our system relies on hydrogen bond formation similar to that in epoxida- tions with peracids and not on direct bonding of the alcoholate to the metal complex as in the vanadium case. These are first hints on the transition state structure for the oxygen transfer in MTO-catalyzed epoxidation.

One advantage of our simple MTO/H,O, epoxidation of alkenes 1 with urea/hydrogen peroxide is the catalytic mode (which can be extended to the preparative scale (cf. Expenmen- tal Procedure; e.g. the epoxidation of 0.5 g of the allylic alcohol l e leads to the epoxide threo-2e in 67% yield [dr 88:12]). In addition, acid-catalyzed secondary reactions (hydrolysis, cleavage, rearrangement) are largely suppressed due to the buffering action of urea, without adversely effecting the reactiv- ity, as is the case when amines are added.IZd] We have also established that the high threo diastereoselectivity for chiral allylic alcohols requires a peracid-like transition state with n-facial control of hydrogen bond formation between oxygen donor and acceptor.

Experimental Procedure

General procedure for the epoxidation of olefins: A solution of MTO (12.3 mg, 49.0 pmol. 0.01 equiv) In CHCI, (10 mL) was mixed with the urea/hydrogen perox- ide adduct (940 mg, 10.0 mmol. 2.00 equiv) and stirred under an argon atmosphere at ca. 20°C for 10 min. The olefin l e (500 mg, 4.99 mmoi, 1.00 equiv) was added dropwise and the suspension stirred for 18 h at about 20 "C, after which 5 mL of water was added The mixture was extracted with CH,CI, (3 x 15 mL). The com- bined organic phases were washed with water (2 x 5 mL) and brine ( 5 mL), dried over MgSO,, and then concentrated at O°C/30 mbar. Conversion 2 9 5 % (deter- mined by 'H NMR analysis). Column chromatography (silica gel, ether/hexane

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(3/1)) of the crude product yielded 391 mg (67%) of the pure epoxy allylic alcohol 2 e with a diastereoselectivity of 88: 12 (threojeryfhro).

Received: April 26. 1995 Revised version: December 8. 1995 [Z 7933 IE]

German version: Angew. Chem. 1996, 108, 578-581

Keywords: asymmetric syntheses . catalysis . complexes with oxygen ligands . epoxidations . rhenium compounds

[l] a) R. A. Sheldon, J. K. Kochi, Metal-Curalysed Oxidations of Organic Com- pounds. Academic Press, New York, 1981; b) H. Mimoun, Angew. Chem. 1982, 94.750-766; Angew. Chem. Int. Ed. Engl. 1982,21,734-750; c) R. H. Holm. Chem. Rei.. 1987.87.1401 - 1449; d) K. A. Jsrgensen, ibid. 1989.89,431-458, e) B. Meunier, ibid. 1992, 92, 1411-1456.

[2] Epoxidation of olefins, oxidation of alkynes to a.8-unsaturated ketones or 1.2-diketones, and Baeyer-Villager rearrangement of ketones: a) W. A. Herr- mdnn. R. W. Fischer, W. Scherer, M. U. Rauch, Angew. Chem. 1993. 105, 1209-1212, Angew. Chem. Inf. Ed. Engl. 1993.32.1187-1160; b) W. A. Herr- mann. R. W. Fischer, D. W Marz, ibid. 1991. 103, 1706-1709 and 1991, 30, 1638-1641; c) H. Yu. H. Simon. Tefrahedron 1991, 47,9035-9052; d) W. A. Herrmann. R. W. Fischer, M. U. Rauch, W Scherer, J. Mol. Cafal. 1994, 86, 243-266; e) W. A. Herrmann, R . W. Fischer, J. D. G. Correia, ibid. 1994, 94, 213 -223; f ) A. M. Al-Ajlouni, 1. H. Espenson, J. Am. Chem. Soc. 1995, 117. 9243- 9250. Oxidation of arenes to pam-quinones: gj W. Adam. W. A. Herr- mann. J. Lin. C. R. Saha-Moller, R. W. Fischer. J. D. G . Correia. Angen. Chcvn. 1994. 106, 2545-2546; Angew Chem. Inf. Ed. Engl. 1994, 33. 2475- 2477; h) W. Adam, W. A. Herrmann, J. Lin, C. R. Saha-Moller, 1 Org. Chem 1994. 59. 8281 8283. i) W. Adam, W. A. Herrmann, C. R. Saha-Moller. M. Shimiru. J. M o t . Cuful. 1995, 97, 15-20. C-H-Insertion: k) R. W. Murray, K. lyanar. J. Chen. J. T. Wearing, Tetrahedron Left. 1995, 36, 6415-6418. Oxida- tion of benraldehydes to phenols: I) S. Yamazaki, Chem. Leff. 1995,127-128. Sulfoxidation: m) P. Huston, J. H. Espenson, A. Bakac, Inorg. Chem. 1993,32. 4517-4523: nj W. Adam. C. M. Mitchell, C. R. Sahd-Molter, Tetrahedron 1994. SO. 13121 -13124; 0 ) K. A. Vassell, J. H. Espenson, Inorg. Chem. 1994, 33. 5491 --5498. Oxidation of nitrogen, phosphorus, arsenic, and antimony: p j Z. Zhu. J. H Espenson, J: Org. Chem. 1995.60, 1326-1332; q) M. M. Abu- Omar, J H. Espenson, Proc 9th Inr. S-ymp. Homog. Catal. 1994; r) M. M. Abu-Omdr, J H. Espenson, J . Am. Chem. Sor. 1995, 117, 272-280.

[3] a ) G. B. Payne. P. H. Deming. P. H. Williams, J Org. Chem. 1961, 26, 659- 663; b) N. Matsumura, N. Sonoda, S. Tsutsumi, Terruhedron Left. 1970, 2029-2032; c) C. H. Gagnieu, A. V. Grouiller, J . Chem. Soc. Perkin Trans 1 1982,1009- 1011 ; d) B. Ben Hassine, M. Gorsane, F Geerts-Evrard, J. Pecher, R. H. Martin. D. Castelet, Bull. SOC. Chim. Belg. 1986, 95, 547-556; e) P. G. Cookson. A. G Davies, N . Fazdl, J: Organomet. Chem 1975,99, C31 -C32; f ) A. A Oswald. D. L. Guertin, J. Org. Chem. 1963, 28, 651-657; g) R. D Tem- ple. Y. Tsuno. J E. Leffler, ibid. 1963,28,2495; h) D. B. Copley, F. Fairbrother, J. R Miller, A. Thompson, Proc. Chem. SOC. 1964,300-301; i) S. D. Cosgrove, W. Jones, J. Chem. Soc. Chem. Commun. 1994, 2255-2256; wealhydrogen peroxide (UHP): k) M. S. Cooper, H. Heaney. A. J. Newbold, W. R. Sander- son. Synlerr 1990,533-535; I ) W. P. Jackson, rbid. 1990,536; m) A. M. d'A. R. Gonsalves, R . A W. Johnstone, M. M. Pereira, I. Shaw, J. Chem. Res. Synops. 1991. 208-209: n) R. Balicki, L. Kaczmarek, P. Nantka-Namirski, Liebigs Ann. Chrm. 1992, 883-884; 0) L. Astudillo, A. Galindo, A. G. Gonzalez, H. Mansilla. Heterocyles 1993, 36. 1075-1080.

[4] N. Yunosuka. S. Shigetsugu, M. Kinjiro, I. Yoshio, M. Toshio, DE-A 2 530 539.1976 (Kao Soap Co. Ltd., Nippon Peroxide Co. Ltd.), [Chem. Absfr. 1976, 84. 152605~1

[ 5 ] T. Schwenkreis. A. Berkessel, Tefrahedron Lett 1993, 34, 4785-4788. [6] A. M. d'A. R Gonsalves, R. A. W. Johnstone, M. M. Pereira, J. Shaw, J . Chem.

[7] a) R. W Hoffmann. Chem. Rev. 1989.89, 1841-1860; b) J. L. Broeker, R. W.

[8] W Adam. B. Nestler, J . Am. Chem. Soc. 1992, 114, 6549-6550. 191 B. E. Rossiter. T. R. Verhoeven. K. B. Sharpless, Tefrahedron Left 1979, 34,

Soc. Perkin Truns. 1. 1991. 645-649.

Hoffmann. K N. Houk, J Am. Chem. SOC. 1991, 113, 5006-5017.

4733- 4736. [lo] W. Adam. B. Nestler. Tefrahedron Left. 1993. 611-614. [I 11 P. Chautemps. JLL. Pierre. Tefrahedron 1976, 32, 549-557.

Diastereoselective Chelation-Controlled Radical Cyclization of Chiral Oxazolidinone-Derived 2-Alkenamides and Modeling of the Transition State** Domenico Badone,* Jean-Marie Bernassau, Rosanna Cardamone. and Umberto Guzzi

The formation of carbon-carbon bonds by radical addition to alkenes is one of the most useful synthetic reactions in organic synthesis.[" Though high a-stereoselection has been observed in radical additions to chiral acceptors, such as r,8-unsaturated amides and imides,['I a high degree of p-stereoselection is diff- cult to achieve and remains a challenge. Recently Curran et al. introduced an auxiliary, derived from Kemp's triacid, that pro- vides high /3-diastereoselectivity in radical addition and annula- tion reactions.I3I However, several steps are required for the preparation of the auxiliary, and development of easier method- ologies is still required.

We now report that the radical cyclization of 1 a,b bearing the oxazolidinone chiral auxiliary R gives 2 with good diastereose- lectivity in the presence of a Lewis acid (Scheme 1 ) . 8-Tetralines like 2, 3, and their derivatives are Vdudbk compounds in phar- maceutical re~earch.'~]

'c. 2

0

l b R = -Br

IC R = -H

Scheme 1. Radical cyclization of 1 a,b.

3

il 'N 0 e Ph Ph

4

Asymmetric 1,4-additions of organometallic reagents to chi- ral aJ-unsaturated N-acyloxazolidinones has been studied, and they show excellent diastereoselecti~ity.~~~ Scheme 2 outlines the synthesis of key intermediates 5 and 6.[61 Coupling of 5 and 6 (DMAP, CHCI,, 60 "C, 8 h) followed by acid hydrolysis of THP ether (AcOH, THF/H,O, 50 "C, 8 h) gave the single diastereo- isomer 7 ( E : Z >99:1) in 50% overall yield. Synthesis of 1a,b was easily carried out (Scheme 3).

Radical generation and cyclization were obtained by three different reaction conditions: addition by syringe pump (3.4 mL h-') of TTMS and AIBN in C6H6 to a solution of 1 a,b (9 x M) in C6H6 at 80 "C (A);"] addition by syringe pump (3.4mLh-')ofSm12 inTHF(0.1M) to l b ( 9 x 1 0 - 3 ~ ) i n T H F / HMPA 95/5 at 25 "C (B);['] stirring ofa solution of 1 b ( l o - ' ~ ) ,

[*] Dr. D. Bddone, Dr. R. Cardamone, Dr U. Guzzi Research Center Sanofi-MIDY. Via Piranesi 38. 1-20137 Milan (Italy) Telefax ' Int. +(2)7394453

Dr. J.-M. Bernassau Sanofi Research Montpellier (France)

[**I In this communication the following abbreviations are used. AIBN = azo- bis(isobutyronitrile), DMAP = 4-(dimethylamino)pyridine, HMPA = hexa- methylphosphoric triamide, PTC = phase-transfer catalysis, PTSA = para- toluenesulfonic acid. THP = tetrahydro-2H-pyran-2-yI. TTMS = tris(tr1- methylsilyl)silane.

Angew. Chem. Int. Ed Engl. 1996, 3S, No. 5 ,c VCH Verlugsgesellschaff mbH, 0-69451 Weinhelm, 1996 0570-0R33~96~35OS-053S 3 lS.OO+ 25 0 535