Aziridination of Chiral 3-(2,2-Dimethyl-1,3-dioxolan-4-yl)-2-propenoate Esters

TETRAHEDRON Pergamon

Tetrahedron 56 (2000) 4515±4519

Aziridination of Chiral 3-(2,2-Dimethyl-1,3-dioxolan-4-yl)-2-propenoate Esters Antonello Fazio,a M. Antonietta Loreto,b,* Paolo A. Tardellaa and Daniela Tofania a

Dipartimento di Chimica, UniversitaÁ `La Sapienza', P. le Aldo Moro 5, I-00185 Rome, Italy Centro C.N.R. per lo Studio della Chimica delle Sostanze Organiche Naturali,² c/o Dipartimento di Chimica, UniversitaÁ `La Sapienza', P. le Aldo Moro 5, I-00185 Rome, Italy

b

Received 22 November 1999; revised 20 March 2000; accepted 6 April 2000

AbstractÐThe reactions of chiral 3-(2,2-dimethyl-1,3-dioxolan-4-yl)-2-propenoate esters 2±5 with NsONHCO2Et and CaO, produce the aziridine derivatives by addition of (ethoxycarbonyl)amino group on the double bond. The stereoselectivity is good for trans substrates. Products are precursors to polyhydroxy amino acids.³ q 2000 Elsevier Science Ltd. All rights reserved.

Introduction Polyhydroxy amino acids arouse wide interest for their presence in many biologically active molecules,1 antibiotics2 and enzymes inhibitors.3 One of the possible synthetic approaches to these compounds is the stereocontrolled introduction and subsequent opening of the aziridine ring in a suitable precursor molecule.4 For many years our research group has been studying a particular aminating reagent: the (ethoxycarbonyl)nitrene (NCO2Et), it can be generated from ethyl N-{[(4-nitrobenzene)sulphonyl]oxy}carbamate (NsONHCO2Et) 1 under basic conditions (Et3N, CH2Cl2)5 or by photolysis of ethyl azidoformate (N3CO2Et)6 and it shows good reactivity with electron rich alkenes such as enamines, silyl ketene acetals and allylsilanes.7 Recently the use of 1 and inorganic insoluble bases such as CaO, K2CO3 in CH2Cl2, permitted the introduction of the aziridine ring on unactivated ole®ns such as a,b-unsaturated esters8 and nitro ole®ns.9 In these cases a possible aza-Michael mechanism may be operative.10

acetonide structure should allow the stereoselective introduction of the aziridine ring, providing a new route to optically active polyhydroxy amino acid derivatives after ring opening and deprotection. Results and Discussion The aziridination reactions carried out on substrates 2±3 using the usual conditions of generation of the (ethoxycarbonyl)nitrene either by a-elimination of 1 with Et3N or by photolysis of N3CO2Et, gave poor yields (,10%) and low diastereoselection causing, in the case of photolysis, the partial trans!cis isomerisation of starting material. Conversely the procedure used in the aziridination of a,b-unsaturated esters,8 i.e. CaO as insoluble inorganic base, low solvent amount, 1:7:7 ratio between substrate and reagents, gave the expected aziridine derivatives 6±9 (Scheme 1) in the reported yields (Table 2, method A). The trans isomer shows a higher diastereoselectivity than the cis isomer. The cis isomer also gives trans aziridines. The products were easily separated by ¯ash-chromatography

In order to gain new information about the mechanism and to further investigate the synthetic potential of this reagent, we analysed the reactivity of 3-(2,2-dimethyl-1,3-dioxolan4-yl)-2-propenoate esters 2±5 (Table 1) in the hypothesis that the presence of a resident chiral g-carbon in the

Table 1. Reaction substrates

Keywords: amination; aziridines; esters; amino acid derivatives. * Corresponding author. Tel.: 139-6-49913668; fax: 139-6-490631; e-mail: [email protected] ² Associated to National Institute of Chemistry of Biological Systems. ³ This work was reported in part at the IV Convegno Nazionale Giornate di Chimica delle Sostanze Naturali, NAT4, September 1997, Salerno (Italy), Abstract P18.

Substrate 2 3 4 5

0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved. PII: S 0040-402 0(00)00293-3

R Et Et Me Me

Double bond con®g.

C4 con®guration

trans cis trans cis

R R S S

4516

A. Fazio et al. / Tetrahedron 56 (2000) 4515±4519

Scheme 1. Aziridination of R diastereomers 2 and 3.

Table 2. Conditions and yields of aziridination of 2 and 3 Substrate

2 2 3 3

Method

A B A B

Substrate: NsONHCO2Et/CaO

Recovered substrate (%)

1:7:7 1:3:3 1:7:7 1:5:5

23 0 25 0

Diastereomeric ratio

Total yield (%)

6

7

8

9

67 65 8 9

33 35 23 10

± ± 27 44

± ± 42 37

37 47 36 42

use of ultrasound or microwaves in reactions in the absence of solvent did not lead to better yields.

on silica gel. Unreacted starting material was partially recovered. Each diastereomer, isolated in the ratios listed in Table 2, was characterised by GC-MS, IR, 1H and 13C NMR analyses.

The stereostructure of products 7 and 9 was con®rmed by comparison with authentic samples prepared from the unprotected aziridines according to the procedure described by JaÈhnisch11 and derivatised by EtOCOCl treatment.12

We also utilised a new procedure, developed for nitro ole®ns by Pellacani and co-workers.10 Using mechanical stirring of 1, CaO and substrate in a mortar, without the presence of solvent (Table 2, method B), we obtained the complete disappearance of the starting material with lower amount of reagents (3±5 equiv.), higher yields (42±47%), shorter reaction times and similar diastereoselection. The

Methyl esters 4 and 5, pseudoenantiomers of 2 and 3, showed similar reactivity and yields. Once again only the trans isomer showed a moderate stereoselection (Scheme 2, Table 3).

Scheme 2. Aziridination of S diastereomers 4 and 5. Table 3. Conditions and yields of aziridination of 4 and 5 Substrate

4 4 5 5

Method

A B A B

Substrate: NsONHCO2Et/CaO

1:7:7 1:5:5 1:7:7 1:5:5

Recovered substrate (%)

40 0 27 0

Diastereomeric ratio

Total yield (%)

10

11

12

13

62 64 8 9

38 36 11 9

± ± 39 43

± ± 42 39

37 45 40 41

A. Fazio et al. / Tetrahedron 56 (2000) 4515±4519

4517

Scheme 3. Stereochemistry of attack in aziridination of 2.

The very low yields of aziridines obtained with substrates like 2±5 in reactions in which the presence of (ethoxycarbonyl)nitrene is usually postulated13 urged us to con®rm the hypothesis that an alternative aza-Michael mechanism may be operating in the heterogeneous phase procedure, in the presence of electron poor ole®ns.9,10 This is con®rmed by the presence of trans con®gured aziridines from cis a,b-unsaturated esters in a reaction of reagent 1 that is unlikely to induce a triplet nitrene. This would explain the partial formation of the more stable trans derivatives 6, 7, 10 and 11 from 3 and 5 through isomerisation of the Ca anionic intermediate before aziridine ring closure.14 As for as the stereoselectivity of reaction is concerned, the aziridine ring is believed to be formed preferentially through b-re attack on compound 2, i.e. from the less hindered side of the molecule in the more stable conformation (Scheme 3). This stereofacial preference is opposite on the compound 4, pseudoenantiomer of 2 (b-Si attack), analogously to the results obtained by Dreiding15 in aziridination reactions using N-aminophthalimide and Pb(OAc)4, where he preferentially obtained the diastereomers corresponding to 10 and con®rmed the structures by X-ray diffraction. The stereofacial preference is con®rmed by chemical correlation of compounds 7 and 9 with the corresponding unprotected aziridines.11 A similar explanation was also suggested by Mulzer and Kappert16 to support the diastereoselectivity of cyclopropanation reactions on substrate 4. Conclusion The results obtained seem to be another example of an aziridination via Michael addition17 in reactions of electron poor ole®ns with NsONHCO2Et and CaO.10 Furthermore, the method of synthesis proposed is a very simple one. It permits, in a few easy handling steps and with low cost reagents, the preparation of building blocks with 3 contiguous chiral centres, potentially useful in the synthesis of polyhydroxy amino acids. Experimental General GC analyses were performed on a HP 5890 Series II gas chromatograph with a capillary column (methyl silicone, length 12.5 m, internal diameter 0.2 mm, ®lm thickness

0.25 mm). GC-MS were done on a HP G1800A GCD system with a capillary column (phenyl methyl silicone, length 30 m, internal diameter 0.25 mm, ®lm thickness 0.25 mm). Microanalyses were carried out on a CE Instruments EA1110. 1H NMR and 13C NMR spectra were obtained in CDCl3 on a Gemini 200 spectrometer. IR spectra in CHCl3 were done by a Perkin±Elmer 1600 Series FTIR spectrometer. Esters 2±5 are commercially available (Fluka and Sigma Aldrich). General procedure Reaction of 2±5 with NsONHCO2Et (method A). To a stirred solution of the substrate (5.0 mmol) in 2.1 ml of CH2Cl2, NsONHCO2Et (5.0 mmol, 1 equiv.) and CaO (5.0 mmol, 1 equiv.) were added every 15 min, reaching the molar ratio substrate: reagents of 1:7:7. During the addition the ¯ask was cooled in water bath to avoid overheating, as the reaction is exothermic. After 24 h stirring, 115 ml of a hexane±CH2Cl2 mixture (10:1) was added. After ®ltration, the organic phase was concentrated in vacuo. The products were puri®ed by ¯ash chromatography on silica gel (hexane/ ethyl acetate, 8:211% Et3N) and isolated in the yields and diastereomeric ratios reported in Tables 2 and 3. Reaction of 2±5 with NsONHCO2Et (method B). In a mortar NsONHCO2Et (1.0 mmol, 1 equiv.) and CaO (1.0 mmol, 1 equiv.) were rapidly added to the substrate (1.0 mmol) and ground for 30 min. Then 2 equiv. of NsONHCO2Et and CaO were added every 1 h and ground continuously, reaching the molar ratio reported in Tables 2 and 3. At the end, 44 ml of a hexane/CH2Cl2 mixture (10:1) were added, the suspension ®ltered and the liquid phase was concentrated in vacuo. The products were puri®ed by ¯ash chromatography on silica gel (hexane/ethyl acetate, 8:211% Et3N) and isolated in the yields and diastereomeric ratios reported in Table 2 and 3. (2R,3R)-1,2-Bis(ethoxycarbonyl)-3-[(4R)-(2,2-dimethyl1,3-dioxolan-4-yl)] aziridine 6. Yellowish oil; GC-MS m/z: 272 (M1215, 15), 140 (30), 112 (30), 84 (37), 43 (100); Anal. Calcd for C13H21NO6: C 54.35, H 7.37, N 4.88. Found: C 54.99, H 7.47, N 4.98; [a ]20 D ˆ29.3 (c 0.75, CHCl3); IR: 1744 cm21; 1H NMR d : 1.26 (t, 3H, CH2CH3), 1.30 (t, 3H, CH2CH3), 1.35 (s, 3H, CCH3), 1.45 (s, 3H, CCH3), 2.95 (dd, 1H, CH (C3), Jˆ3 and 6 Hz), 3.08 (d, 1H, CH (C2), Jˆ3 Hz), 3.89 (dd, 1H, CHHO (C5), Jˆ6 and 7 Hz), 4.00 (dd, 1H, CHHO (C5), Jˆ6 and 9 Hz), 4.25±4.15 (m, 5H, CO2CH2, NCO2CH2, CHO (C4)); 13C NMR d : 14.05 (CH2CH3), 14.23 (CH2CH3), 25.18 (CCH3), 26.47 (CCH3), 39.02 (CHN (C3)), 44.47 (CHN (C2)), 62.01 (CH2CH3), 62.83 (CH2CH3), 67.68 (CH2O (C5)), 74.82 (CHO (C4)), 110.27 (C(CH3)2), 159.58 (NCO2), 167.49 (CCO2).

4518

A. Fazio et al. / Tetrahedron 56 (2000) 4515±4519

(2S,3S)-1,2-Bis(ethoxycarbonyl)-3-[(4R)-(2,2-dimethyl1,3-dioxolan-4-yl)] aziridine 7. Yellowish oil; GC-MS m/z: 272 (M1215, 17), 156 (28), 140 (23), 112 (35), 84 (48), 56 (29), 43 (100), 41 (24); Anal. Calcd for C13H21NO6: C 54.35, H 7.37, N 4.88. Found: C 54.65, H 7.40, N 5.02; 21 1 [a ]20 D ˆ22.2 (c 1.5, CHCl3); IR: 1743 cm ; H NMR d : 1.26 (t, 3H, CH2CH3), 1.30 (t, 3H, CH2CH3), 1.34 (s, 3H, CCH3), 1.41 (s, 3H, CCH3), 2.97 (dd, 1H, CH (C3), Jˆ3 and 4 Hz), 3.14 (d, 1H, CH (C2), Jˆ3 Hz), 3.90 (dd, 1H, CHHO (C5), Jˆ6 and 9 Hz), 4.12 (dd, 1H, CHHO (C5), Jˆ6 and 9 Hz), 4.15±4.28 (m, 5H, CO2CH2, NCO2CH2, CHO (C4)); 13 C NMR d : 14.09 (CH2CH3), 14.25 (CH2CH3), 25.51 (CCH3), 26.34 (CCH3), 37.95 (CHN (C3)), 43.65 (CHN (C2)), 61.97 (CH2CH3), 62.80 (CH2CH3), 66.54 (CH2O (C5)), 73.02 (CHO (C4)), 110.11 (C(CH3)2), 159.89 (NCO2), 167.68 (CCO2). (2S,3R)-1,2-Bis(ethoxycarbonyl)-3-[(4R)-(2,2-dimethyl1,3-dioxolan-4-yl)] aziridine 8. Yellow oil; GC-MS m/z: 272 (M1215, 23), 156 (22), 140 (23), 112 (35), 84 (43), 72 (22), 68 (30), 43 (100); Anal. Calcd for C13H21NO6: C 54.35, H 7.37, N 4.88. Found: C 54.02, H 7.03, N 4.50; 21 1 [a ]20 D ˆ221.1 (c 1.4, CHCl3); IR: 1735 cm ; H NMR d : 1.29 (t, 3H, CH2CH3), 1.31 (t, 3H, CH2CH3), 1.33 (s, 3H, CCH3), 1.47 (s, 3H, CCH3), 2.80 (dd, 1H, CH (C3), Jˆ7 and 8 Hz), 3.16 (d, 1H, CH (C2), Jˆ7 Hz), 3.77 (dd, 1H, CHHO (C5), Jˆ6 and 9 Hz), 3.97 (dd, 1H, CHHO (C5), Jˆ6 and 9 Hz), 4.33±4.09 (m, 5H, CO2CH2, NCO2CH2, CHO (C4)); 13 C NMR d : 13.91 (CH2CH3), 14.00 (CH2CH3), 25.18 (CCH3), 26.61 (CCH3), 38.23 (CHN (C3)), 44.28 (CHN (C2)), 62.23 (CH2CH3), 63.74 (CH2CH3), 66.63 (CH2O (C5)), 73.95 (CHO (C4)), 110.24 (C(CH3)2), 160.73 (NCO2), 162.81 (CCO2). (2R,3S)-1,2-Bis(ethoxycarbonyl)-3-[(4R)-(2,2-dimethyl1,3-dioxolan-4-yl)] aziridine 9. Yellow oil;. GC-MS m/z: 272 (M1215, 19), 156 (26), 112 (32), 84 (47), 68 (23), 56 (22), 43 (100); Anal. Calcd for C13H21NO6: C 54.35, H 7.37, N 4.88. Found: C 54.05, H 7.20, N 4.92; [a ]20 D ˆ140.4 (c 0.4, CHCl3); IR: 1743 cm21; 1H NMR d : 1.29±1.25 (m, 9H, 2 CH2CH3, CCH3), 1.44 (s, 3H, CCH3), 2.77 (dd, 1H, CH (C3), Jˆ6 and 8 Hz), 3.24 (d, 1H, CH (C2), Jˆ6 Hz), 4.05± 4.35 (m, 7H, CO2CH2, NCO2CH2, CHO (C4), CH2O (C5)); 13 C NMR d : 14.08 (CH2CH3), 14.19 (CH2CH3), 25.07 (CCH3), 26.90 (CCH3), 38.91 (CHN (C3)), 44.32 (CHN (C2)), 61.88 (CH2CH3), 63.36 (CH2CH3), 68.17 (CH2O (C5)), 72.41 (CHO (C4)), 110.14 (C(CH3)2), 161.04 (NCO2), 166.73 (CCO2). (2S,3S)-3-[(4S)-(2,2-Dimethyl-1,3-dioxolan-4-yl)]-1-ethoxycarbonyl-2-methoxycarbonyl aziridine 10. Yellow oil; GC-MS m//z: 273 (M1, 0.5), 258 (43), 172 (28), 126 (66), 114 (21), 100 (21), 84 (36), 72 (28), 59 (36), 43 (100); Anal. Calcd for C12H19NO6: C 52.74, H 7.01, N 5.13. Found: C 52.85, H 7.12, N 5.12; [a ]20 D ˆ152,6 (c 0.9, CHCl3); IR: 1744 cm21; 1H NMR d : 1.25 (t, 3H, CH2CH3), 1.34 (s, 3H, CCH3), 1.45 (s, 3H, CCH3), 2.94 (dd, 1H, CH (C3), Jˆ3 and 6 Hz), 3.10 (d, 1H, CH (C2), Jˆ3 Hz), 3.78 (s, 3H, CO2CH3), 3.89 (q, 1H, CHHO (C5), Jˆ6 Hz), 3.99 (dd, 1H, CHHO (C5), Jˆ6 and 9 Hz), 4.12±4.21 (m, 3H, CHO (C4), CH2CH3); 13C NMR d : 14.23 (CH2CH3), 25.16 (CCH3), 26.44 (CCH3), 38.76 (CHN (C3)), 44.63 (CHN (C2)), 52.77 (CO2CH3), 62.91 (CH2CH3), 67.68 (CHO

(C4)), 74.82 (CH2O (C5)), 110.30 (C(CH3)2), 159.53 (NCO2), 168.00 (CCO2). (2R,3R)-3-[(4S)-(2,2-Dimethyl-1,3-dioxolan-4-yl)]-1-ethoxycarbonyl-2-methoxycarbonyl aziridine 11. Yellow oil; GC-MS m//z: 273 (M1, 0.5), 258 (43), 156 (32), 126 (59), 84 (52), 59 (43), 43 (100), 42 (39), 41 (41); Anal. Calcd for C12H19NO6: C 52.74, H 7.01, N 5.13. Found: C 52.95, H 21 7.05, N 5.12; [a ]20 D ˆ122.3 (c 0.2, CHCl3); IR: 1743 cm ; 1 H NMR d : 1.25 (t, 3H, CH2CH3), 1.33 (s, 3H, CCH3), 1.40 (s, 3H, CCH3), 2.97 (dd, 1H, CH (C3), Jˆ3 and 4 Hz), 3.14 (d, 1H, CH (C2), Jˆ3 Hz), 3.77 (s, 3H, CO2CH3), 3.86±3.91 (m, 2H, CH2O (C5)), 4.11 (q, 2H, CH2CH3), 4.12±4.23 (m, 1H, CHO (C4)); 13C NMR d : 13.95 (CH2CH3), 25.28 (CCH3), 26.14 (CCH3), 37.57 (CHN (C3)), 43.64 (CHN (C2)), 52.62 (CO2CH3), 62.81 (CH2CH3), 66.44 (CH2O (C5)), 72.96 (CHO (C4)), 110.21 (C(CH3)2), 163.06 (NCO2), 168.40 (CCO2). (2R,3S)-3-[(4S)-(2,2-Dimethyl-1,3-dioxolan-4-yl)]-1-ethoxycarbonyl-2-methoxycarbonyl aziridine 12. Yellowish oil; GC-MS m//z: 273 (M1, 0.5), 258 (41), 126 (52), 98 (29), 84 (37), 59 (32), 56 (17), 43 (100); Anal. Calcd for C12H19NO6: C 52.74, H 7.01, N 5.13. Found: C 52.88, H 7.18, N 5.18; 21 1 [a ]20 D ˆ129.6 (c 0.5, CHCl3); IR: 1742 cm ; H NMR d : 1.28 (t, 3H, CH2CH3), 1.31 (s, 3H, CCH3), 1.46 (s, 3H, CCH3), 2.81 (dd, 1H, CH (C3), Jˆ6 and 8 Hz), 3.28 (d, 1H, CH (C2), Jˆ6 Hz), 3.74 (dd, 1H, CHHO (C5), Jˆ7 and 9 Hz), 3.81 (s, 3H, CO2CH3), 4.02±4.22 (m, 4H, CH2CH3, CHO (C4), CHHO (C5)); 13C NMR d : 14.17 (CH2CH3), 25.05 (CCH3), 26.90 (CCH3), 38.75 (CHN (C3)), 44.41 (CHN (C2)), 52.74 (CO2CH3), 63.40 (CH2CH3), 68.12 (CH2O (C5)), 72.40 (CHO (C4)), 110.21 (C(CH3)2), 160.97 (NCO2), 167.21 (CCO2). (2S,3R)-3-[(4S)-(2,2-Dimethyl-1,3-dioxolan-4-yl)]-1-ethoxycarbonyl-2-methoxycarbonyl aziridine 13. Yellowish oil; GC-MS m//z: 273 (M1, 0.5), 258 (47), 126 (57), 84 (54), 59 (38), 43 (100); Anal. Calcd for C12H19NO6: C 52.74, H 7.01, N 5.13. Found: C 52.90, H 7.07, N 5.15; [a ]20 D ˆ22.6 (c 0.4, CHCl3); IR: 1742 cm21; 1H NMR d : 1.28 (t, 3H, CH2CH3), 1.34 (s, 3H, CCH3), 1.48 (s, 3H, CCH3), 2.82 (t, 1H, CH (C3), Jˆ7 Hz), 3.20 (d, 1H, CH (C2), Jˆ7 Hz), 3.77 (s, 3H, CO2CH3), 3.79 (dd, 1H, CHHO (C5), Jˆ6 and 9 Hz), 3.99 (dd, 1H, CHHO (C5)), Jˆ6 and 9 Hz), 4.10±4.24 (m, 1H, CHO (C4)), 4.19 (q, 2H, CH2CH3); 13C NMR d : 14.17 (CH2CH3), 25.32 (CCH3), 26.68 (CCH3), 38.22 (CH (C3)), 44.38 (CH (C2)), 52.68 (CO2CH3), 63.41 (CH2CH3), 66.67 (CH2O (C5)), 73.84 (CHO (C4)), 110.29 (C(CH3)2), 161.20 (NCO2), 167.30 (CCO2). Reaction of (2R,3R)-3-[(4S)-(2,2-dimethyl-1,3-dioxolan4-yl)]-2-ethoxycarbonyl-aziridine and (2R,3S)-3-[(4S)(2,2-dimethyl-1,3-dioxolan-4-yl)]-2-ethoxycarbonyl aziridine with EtOCOCl. (2R,3R)-3-[(4S)-(2,2-dimethyl-1,3dioxolan-4-yl)]-2-ethoxycarbonyl-aziridine (0.10 g, 0.47 mmol), prepared from ethyl 2-bromo-3-[(4S)-(2,2dimethyl-1,3-dioxolan-4-yl)-2-propenoate],11 was dissolved in a solution of triethylamine (0.30 g, 3.0 mmol) and anhydrous ethyl ether (1.0 ml). To the mixture EtOCOCl (0.35 g, 3.2 mmol) in 0.25 ml of anhydrous ethyl ether was added dropwise, under cooling in an ice±salt bath and with a vigorous stirring. After 1 h the triethylamine hydrochloride

A. Fazio et al. / Tetrahedron 56 (2000) 4515±4519

was removed by ®ltration. After the solvent was evaporated, the residual was analysed by GC, GC-MS and 1H NMR. Spectral data were identical to those of the aziridine 6. Starting from (2R,3S)-3-[(4S)-(2,2-dimethyl-1,3-dioxolan4-yl)]-2-ethoxycarbonyl-aziridine, GC, GC-MS and 1H NMR of the obtained product were identical to those of the aziridine 9. Acknowledgements We thank the Italian Ministero dell'UniversitaÁ e della Ricerca Scienti®ca e Tecnologica (MURST), the University `La Sapienza' of Rome (National Project `Stereoselezione in Sintesi Organica. Metodologie ed Applicazioni') and the Consiglio Nazionale delle Ricerche (CNR) for ®nancial support. References 1. Isono, K.; Nagatsu, J.; Kawashima, Y.; Suzuki, S. Agric. Biol. Chem. 1965, 29, 848±854. 2. (a) Mzengeza, S.; Whitney, R. A. J. Org. Chem. 1988, 53, 4074±4081. (b) Madau, A.; Porzi, G.; Sandri, S. Tetrahedron: Asymmetry 1996, 7, 825±830. 3. Wagner, I.; Musso, H. Angew. Chem. Int. Ed. Engl. 1983, 22, 816±828.

4519

4. Tanner, D. Angew. Chem. 1994, 106, 625±643; Angew. Chem., Int. Ed. Engl. 1994, 33, 599±619. 5. Lwowski, W.; Maricich, T. J. J. Am. Chem. Soc. 1965, 87, 3630±3637. 6. Lwowski, W.; Mattingly Jr, T. W. J. Am. Chem. Soc. 1965, 87, 1947±1958. 7. Fioravanti, S.; Loreto, M. A.; Pellacani, L.; Raimondi, S.; Tardella, P. A. Tetrahedron Lett. 1993, 34, 4101±4104. 8. Carducci, M.; Fioravanti, S.; Loreto, M. A.; Pellacani, L.; Tardella, P. A. Tetrahedron Lett. 1996, 37, 3777±3778. 9. Fioravanti, S.; Pellacani, L.; Stabile, S.; Tardella, P. A.; Ballini, R. Tetrahedron Lett. 1997, 38, 3309±3310. 10. Fioravanti, S.; Pellacani, L.; Stabile, S.; Tardella, P. A.; Ballini, R. Tetrahedron 1998, 54, 6169±6176. 11. JaÈhnisch, K. Liebigs Ann./Recueil 1997, 757±760. 12. Ikawura, Y.; Nabeya, A. J. Org. Chem. 1960, 25, 1118±1123. 13. Conaghy Jr., J. S.; Lwowski, W. J. Am. Chem. Soc. 1967, 89, 2357±2364 (see also pp 4450±4456). 14. Apeloig, Y.; Karni, M.; Rappoport, Z. J. Am. Chem. Soc. 1983, 105, 2784±2793. We thank Prof. Z. Rappoport for helpful discussion on this point. 15. Chilmonczyk, Z.; Egli, M.; Behringer, C.; Dreiding, A. S. Helv. Chim. Acta 1989, 72, 1095±1106. 16. Mulzer, J.; Kappert, M. Angew. Chem. Int. Ed. Engl. 1983, 22, 63±64. 17. Atkinson, R. S. Tetrahedron 1999, 55, 1519±1559.