Antimony Trichloride: a Mild and Efficient Reagent for Chemoselective Ring Opening of Oxiranes

Indian Journal of Chemistry Vol. 51B, January 2012, pp. 302-307

Antimony trichloride: A mild and efficient reagent for chemoselective ring opening of oxiranes

Gourhari Maiti*, R N Bhattacharya & Rajiv Karmakar Department of Chemistry, Jadavpur University, Kolkata 700 032, India E-mail: [email protected] Received 6 January 2011; accepted (revised) 29 September 2011

Antimony trichloride mediates regioselective, stereoselective and chemoselective ring opening of oxiranes under mild laboratory conditions with semiquantative yields. A new route to α-acetoxychalcones is also explored.

Keywords: Ring opening, oxiranes, stereoselective, chemoselective, α-acetoxychalcones, antimony trichloride

Epoxides are valuable intermediates in organic were investigated for the reaction. Out of these, synthesis as they serve as illogical electrophile and acetonitrile proved to be the best in terms of both their nucleophilic cleavage leads to 1,2 difunctionali- reaction time and yield. zed systems and also because it usually leads to trans- Monoaryl oxiranes on similar treatment furnished stereochemistry1. Conversion of epoxides to halo- products which were formed in accordance with hydrins had been studied extensively with a variety of Markownikoffs’ rule, the chlorine being attached to reagents like magnesium halides, SnCl2.2H2O, the carbon which could form the most stable TMSCl, alkylammonium halides, thionyl chloride, carbocation (Table I, entries 6-10). zirconyl chloride, etc2. Chlorohydrins and other For aliphatic epoxides, steric effect was dominant halohydrins gain importance from the fact that they and the product of steric control was formed. The are intermediates in the synthesis of a vast range of chlorine atom attached itself to the least substituted biologically active natural and synthetic products, carbon atom. (Table I, entries 10-13) (Ref 2a). In unnatural amino acids and chiral auxiliaries for compound 2m both chlorine atoms are attached to the asymmetric synthesis3. They also find application in terminal carbons as supported by the 1H and 13C NMR the synthesis of homochiral β-blockers. Because of data. A 4H doublet in 1H NMR and only two peaks at these synthetic utilities, a newer, cheap and accessible δ 46.2 and 71.3 confirmed the proposed structure. method for transformation of epoxides to halohydrins Had the chlorine not been on the terminal carbon, is still in demand and a field of active research there would be no peak at about δ 46 in the 13C NMR interest. In continuation of the work on exploring the spectrum for all the compounds (2k - 2m). Exclu- scope of antimony trichloride (SbCl3) as catalyst and sively threo-isomers were obtained from chalcone reagent in organic transformation4, herein is epoxides1b,5. investigated the ring opening of epoxides w ith SbCl3 To confirm the regioselectivity and stereo- (Scheme I). selectivity of the reaction, X-ray crystallographic analysis of 3-chloro-2-hydroxy-1-phenyl-3-p-tolyl- Results and Discussions propan-1-one was performed (2b, Table I, entry 2, The reaction of oxiranes with antimony trichloride Figure 1) (Ref 6). The structure revealed that in case gave high yield of ring opening products and was of epoxy derivative of chalcones, the chloride ion found to be regioselective, stereoselective and from SbCl3 attacked the β-carbon from the carbonyl chemoselective. Reaction of SbCl3 with epoxides group and the OH group was attached to the α-carbon derived from chalcones and monoaryloxiranes did and was cis to the chlorine atom. As mentioned proceed smoothly to furnish halohydrins as exclusive earlier, epoxides usually undergo ring opening leading product. Various solvents such as DCM, DMF, to the trans product. Formation of the cis chloro- ethylene glycol, ethanol, nitromethane and acetonitrile hydrin could be explained by initial complexation of

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O O Cl O SbCl3, CH3CN R R 15-20 min, RT OH Cl O

SbCl3, CH3CN R R 15-20 min, RT OH

O OH R SbCl3, CH3CN Cl R 15-20 min, RT

Scheme I

Table I — Reaction of epoxides with antimony trichloridea

Entryc Substrate Product Yield (%)b O O Cl O 1 Ph Ph 88 OH 1a 2a O O Cl O 2 Ph Ph 92 OH 1b 2b O O Cl O 3 Ph Ph 89 OH 1c Cl 2c Cl O O O Cl 4 Ph Ph 90 OH 1d OMe 2d OMe O O O Cl NO2 NO 5 Ph Ph 2 92 OH 1e 2e O Cl OH 6 90

1f 2f O Cl OH 7 92 Cl 1g Cl 2g O Cl OH 8 90 MeO 1h MeO 2h —Contd

304 INDIAN J. CHEM., SEC B, JANUARY 2012

Table I — Reaction of epoxides with antimony trichloridea—Contd

Entryc Substrate Product Yield (%)b O Cl OH 9 91

1i 2i O Cl OH 10 93 Br Br 1j 2j O OH O O 11 92 1k 2k Cl O OH O O 12 94 Cl 1l 2l O OH 13 Cl Cl Cl 90 1m 2m a Reaction condition: epoxide (1.0 mmol), SbCl3 (0.5 mmol) in 3 mL acetonitrile, b c RT. Pure and isolated yield. For Entries 7-13, 1.2 mmol of SbCl3 was used

Figure 1 — X-ray structure of 3-chloro-2-hydroxy-1-phenyl-3-p-tolylpropan-1-one (2b, Table I, entry 2)

δ SbCl3 with oxo group and oxygen atom of the epoxide doublet with coupling constant 2.1 Hz at 5.24 and a ring. Then nucleophilic attack of chloride in an one proton multiplet at δ 5.38-5.42. In D2O solvent, intramolecular fashion from the same side of the the peak at δ 4.11 disappeared and the peaks at δ 5.24 oxygen atom led to only a small dihedral angle and 5.39 appeared as sharp one proton doublets with between OH and Cl in the resulting chlorohyhrin coupling constant 2.1 Hz which revealed that the peak (Scheme I). at δ 4.11 was due to OH proton, the peak at δ 5.24 due 1 H NMR spectra of 2b (Table I, entry 2) showed a to H-C-Cl and the peak at δ 5.39 due to H-C-OH. For one proton broad singlet at δ 4.11, a one proton all the compounds of the series 2a-f, the H-C-Cl had

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1 1 R O R SbCl3, CH3CN CHO R2 15-20 min, RT R2

Scheme II — Ring opening of stilbene epoxides with SbCl3

a Table II — Ring opening of stilbene epoxides with SbCl3 Experimental Section

c General experimental procedure Entry Substrate Product Yield b (%) To a solution of an epoxide (1.0 mmol) in 3 mL O Ph acetonitrile, SbCl3 (0.5 mmol for Table I, entries 1-5, 1 Ph CHO 89 1.2 mmol for Table I, entries 6-13, 0.2 mmol for Ph Ph 3a Table II, entries 1-4) was added and stirred at RT for O Ph 20 min. The progress of the reaction was monitored 2 CHO 90 by TLC. On completion of Ph Ph Ph 3a reaction, the reaction mixture was quenched with water, extracted with DCM, dried over anhydrous O Ph Ph Na SO and the DCM layer concentrated and purified 3 CHO 88 2 4 by short column chromatography over silica gel by Ph Ph 3b eluting with 8-25% ethyl acetate- petroleum ether.

O Ph Ph 4 CHO 90 Spectral data 1 p-tolyl p-tolyl H NMR spectra were recorded with a Bruker 300 3c (300 MHz) spectrometer as solutions in CDCl3.

a Chemical shifts are expressed in δ (ppm) and are Reaction condition: epoxide (1.0 mmol), SbCl3 (0.2 mmol) in 3 mL acetonitrile, RT, 20 min. bPure and isolated yield. referenced to TMS as an internal standard. All cProducts were characterized by 1H and 13C NMR. coupling constants are absolute values and are expressed in Hz. The description of the signals include: s = singlet, d = doublet, t = triplet, m = coupling constant value of about 2.1 Hz indicating multiplet and dd = doublet of doublet. 13C NMR that the compounds had syn orientation of OH and Cl. spectra were recorded with a Bruker 300 (75 MHz) However, 1,2-diaryloxiranes when subjected to the spectrometer as solutions in CDCl3 with complete same reaction condition or even catalytic amount of proton decoupling. 1 catalyst, underwent a rearrangement (Scheme II) to 2a: Off-white solid, m.p. 77°C. H NMR (300 7 produce diaryl acetaldehydes as the sole product . MHz, CDCl3): δ 4.12 (d, J = 7.5 Hz, 1H), 5.25 (d, J = This was formed via 1,2-shift of an aryl group on the 2.1 Hz, 1H), 5.41(dd, J = 2.1, 7.5 Hz, 1H), 7.32-7.45 electron deficient carbon atom (Table II). (m, 3H), 7.51-7.63 (m, 4H), 7.68-7.78 (m, 1H) 7.94 13 (d, J = 7.2 Hz, 2H); C NMR (75 MHz, CDCl3): δ Prior to the determination of X-ray structure, a 62.8, 75.0, 126.4, 126.9, 127.4, 127.6, 128.1, 129.2, reaction was performed to confirm the β-attachment 132.7, 133.5, 198.2. of chlorine atom. This provided a route to α-acetoxy 1 2b: White solid, m.p. 83°C. H NMR (300 MHz, chalcones (Table III), an as yet unexplored class of CDCl ): δ 2.36 (s, 3H), 4.11 (d, J = 6.0 Hz, 1H), 5.24 compounds (Scheme III). The aforesaid compounds 3 (d, J = 2.1 Hz, 1H), 5.38-5.42 (m, 1H), 7.19 (d, J = were formed via acetylation followed by elimination 8.1 Hz, 2H), 7.44 (d, J = 8.1 Hz, 2H), 7.52-7.59 (m, in one pot. 13 2H), 7.64-7.71 (m, 1H), 7.91-7.96 (m, 2H); C NMR In conclusion antimony trichloride mediates (75 MHz, CDCl3): δ 21.1, 63.8, 76.2, 127.8, 128.6, regioselective, stereoselective and chemoselective 129.1, 129.2, 133.7, 134.2, 135.2, 138.7, 197.8. ring opening of oxiranes under mild laboratory 2c: Off-white solid, m.p. 91°C. 1H NMR (300 reaction conditions with semiquantative yields. MHz, CDCl3): δ 4.14 (d, J = 6.9 Hz, 1H), 5.21 (d, J =

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O Cl O

Pyridine, Ac2O 1 2 R1 R2 R R DMAP OAc OH

Scheme III

α a 13 Table III — Synthesis of -acetoxy chalcones C NMR (75 MHz, CDCl3): δ 20.7, 128.4, 128.8,

1 2 b,c 129.4, 129.5, 130.0, 130.3, 132.2, 132.5, 136.9, Entry R R Yield (%) Product 144.6, 168.5, 190.6. 1 H H 88 4a 4b: Colourless viscous liquid. 1H NMR (300 2 H 4-OMe 90 4b MHz, CDCl3): δ 2.34 (s, 3H), 3.89 (s, 3H), 6.81 (s, 3 H 4-Me 90 4c 1H), 6.97 (d, J = 9.0 Hz, 2H), 7.31-7.42 (m, 3H), 13 aReaction condition: halohydrin (1.0 mmol), acetic anhydride 7.55-7.65 (m, 2H), 7.90 (d, J = 9.0 Hz, 2H); C b (1,1 mmol), DMAP (0.1 mmol), 2 mL pyridine, RT, 8 hr. Pure NMR (75 MHz, CDCl3): δ 20.7, 55.4, 113.7, 128.0, c 1 13 and isolated yield. Products were characterized by H and C 128.7, 129.3, 129.6, 130.1, 131.8, 132.3, 144.6, NMR 163.3, 168.4, 189.3. 1 2.1 Hz, 1H), 5.32-5.42 (m, 1H), 7.36 (d, J = 8.7 Hz, 4c: Colourless viscous liquid. H NMR (300 MHz, 2H), 7.50 (d, J = 8.7 Hz, 2H), 7.57 (t, J = 7.8 Hz, 2H), CDCl3): δ 2.36 (s, 3H), 2.40 (s, 3H), 6.89 (s, 1H), 7.23 13 (d, J = 8.1 Hz, 2H), 7.45-7.65 (m, 5H), 7.84-7.90 (m, 7.65-7.73 (m, 1H), 7.92 (d, J = 7.8 Hz, 2H); C NMR 13 2H); C NMR (75 MHz, CDCl3): δ 20.8, 21.6, 128.4, (75 MHz, CDCl3): δ 62.9, 75.8, 128.5, 128.7, 129.2, 129.4, 133.5, 134.4, 134.7, 136.6, 197.4. 129.5, 129.7, 130.0, 130.4, 132.4, 137.2, 140.6, 144.1, 168.5, 190.7. 2d: Off-white solid, m.p. 88°C. 1H NMR (300 MHz, CDCl3): δ 3.91 (s, 3H), 4.22 (brs, 1H), 5.26 (d, Acknowledgements J = 2.1 Hz, 1H), 5.32-5.40 (m, 1H), 7.02 (dd, J = 2.1, 7.2 Hz, 2H), 7.30-7.41 (m, 3H), 7.54-7.60 (m, 2H), The authors gratefully acknowledge the financial 7.94 (dd, J = 2.1, 6.9 Hz, 2H); 13C NMR (75 MHz, and infrastructural support from UGC-CAS and PURSE-DST programme of the Department of CDCl3): δ 55.7, 64.3, 75.6, 114.4, 126.2, 128.0, 128.6, 128.8, 131.0, 138.4, 164.5, 195.9. Chemistry, Jadavpur University. RK thanks CSIR, New Delhi for award of fellowship. 2k: Pale yellow liquid. 1H NMR (300 MHz, CDCl ): δ 2.66 (d, J = 5.1Hz, 1H), 3.70-3.83 (m, 3 References 2H), 4.00-4.10 (m, 2H), 4.18-4.25 (m, 1H), 6.85- 7.01 (m, 3H), 7.28-7.39 (m, 2H); 13C NMR (75 1 (a) Sarangi C, Das N B, Nanda B & Nayak A, J Chem Res, 1, 1997, 180; (b) House H O, J Org Chem, 21, 1956, 1306. MHz, CDCl3): δ 46.4, 69.0, 70.5, 115.1, 122.0, 130.2, 158.2 (Ref 2a). 2 (a) Aghapour G, Afzali A & Salek F, Indian J Chem, 48B, 2l: Pale yellow liquid. 1H NMR (300 MHz, 2009, 231 and references cited therein; (b) Das B, Krishnaiah δ J M & Venkateswarlu K, Chem Lett, 36, 2007, 82 and references CDCl3): 2.32 (s, 3H), 2.97 (brs, 1H), 3.78 (dd, = cited therein. 5.5, 11.3Hz, 1H), 4.04-4.10 (m, 2H), 4.21 (dd, J = 5.3, 11.3Hz, 1H), 4.21(quintet, J = 5.3Hz, 1H), 6.84 (d, J 3 (a) Bartlett P A, in Assymetric Synthesis, Vol. 3, edited by J D = 8.1Hz, 2H), 7.11 (d, J = 8.1Hz, 2H); 13C NMR (75 Morrison (Academic Press, Orlando), 1984, p.411; (b) Fenical MHz, CDCl ): δ 20.5, 46.0, 68.8, 69.9,114.5, 130.0, W, in Marine Natural Products, Vol. 2, edited by P J Scheuer 3 (Academic Press, New York), 1980, p.174. 130.7,156.1. 2m: Colourless liquid. 1H NMR (300 MHz, 4 (a) Maiti G & Kundu P, Tetrahedron Lett, 47, 2006, 5733; (b) Maiti G & Kundu P, Synth Commun, 37, 2007, 2309; (c) CDCl3): δ 2.67 (brs, 1H), 3.68 (d, J = 5.1Hz, 4H), 13 Bhattacharya R N, Kundu P & Maiti G, Synth Commun, 40, 4.00-4.14 (m, 1H); C NMR (75 MHz, CDCl3): δ 2010, 476. 71.3, 46.2 (Ref 2a). 1 5 (a) Xu L W, Li L, Xia C G & Zhao P Q, Tetrahedron Lett, 45, 4a: Colourless viscous liquid. H NMR (300 2004, 2435; (b) Das B, Venkateswarlu K & Krishnaiah M, MHz, CDCl3): δ 2.36 (s, 3H), 6.89 (s, 1H), 7.35-7.56 Helv Chem Acta, 90, 2007, 149; (c) Einhorn C & Luche J L, (m, 5H), 7.57-7.68 (m, 3H), 7.86-7.93 (m, 2H); Chem Commun, 1986, 1368.

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