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Synlett. Author manuscript; available in PMC 2009 November 2.
Published in final edited form as: Synlett. 2008 April 1; 2008(7): 9991004. doi:10.1055/s-2008-1072513.

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Julia Olefination as a General Route to Phenyl (-Fluoro)vinyl Sulfones

Maggie He1, Arun K. Ghosh, and Barbara Zajc* Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, NY 10031, USA

Abstract
Mild and efficient synthesis of phenyl (-fluoro)vinyl sulfones via condensation of aldehydes and a ketone with a novel benzothiazolyl based bis-sulfone reagent is reported and this proceeds with moderate to good Z-stereoselectivity.

Keywords fluorination; olefination; Julia; fluorovinyl sulfones; benzothiazole Herein we report the development and application of a novel reagent for the preparation of phenyl (-fluoro)vinyl sulfones. Sulfones in general are important synthetic intermediates, leading to a variety of compounds.2 Specifically, (-fluoro)vinyl sulfones have been subjected to a range of transformations, such as desulfonylation leading to vinyl fluorides,3 stannyldesulfonylation,4 or silyl and germyldesulfonylation,5 and thus they serve as versatile synthetic intermediates to a variety of fluoroolefins. Also, vinyl sulfones can be used for cycloadditions and are Michael acceptors.3b,6 (-Fluoro)vinyl sulfones can be prepared by various approaches, such as: addition of fluoromethyl phenyl sulfone anion to carbonyl compounds,3a Horner-Wadsworth-Emmons3-5 or Peterson's olefination,7 syn elimination of sulfoxides,8 or via electrochemical method.9 Synthesis of vinyl fluorides using fluorobis (phenylsulfonyl)methane has also been shown.10 An attractive method for the synthesis of carbon-carbon double bonds is the modified or one-pot Julia-Kocienski olefination.11 The use of Julia reaction for the synthesis of vinyl fluorides has recently begun to receive attention. 12,13 In this context, our synthesis of vinyl fluorides hinges on development of general routes to fluorinated 1,3-benzothiazolyl sulfones via metalationelectrophilic fluorination.13 The fluoro 1,3-benzothiazol-2-yl sulfones so derived were subjected to condensations with a series of aldehydes and ketones to afford high yields of regiospecifically fluorinated 1,2-diaryl olefins13a as well as -fluoro acrylates.13b Encouraged by these results, we decided to explore the utility of Julia olefination for the synthesis of phenyl (-fluoro)vinyl sulfones. Briefly, our synthesis of the desired reagent for the preparation of phenyl (-fluoro)vinyl sulfones via modified Julia olefination initially commenced from the commercially available chloromethyl phenyl sulfone. Displacement of chloride with the sodium salt of 2-mercapto-1,3benzothiazole provided the mono sulfone 1, however the conversion proceeded only at high T. In order to increase the reactivity of the halomethyl phenyl sulfone, the iodo derivative was synthesized (sodium benzenesulfinate and CH2I2)14. As anticipated, reaction of the iodomethyl
Thieme Stuttgart New York Fax: +1(212)6506107 E-mail: [email protected]. (1)Undergraduate research participant.

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sulfone derivative proceeded at the milder 70 C to give 1 in 83% isolated yield, that was subjected to oxidation to bis-sulfone 2 using catalytic ammonium molybdate [(NH4)6Mo7O244H2O] and H2O215 (75%, Scheme 1). Subsequent fluorination of 2 using NaH and Selectfluor in THF resulted in a mixture of starting 2, monofluoro 3 and difluoro 4 derivatives (39%:55%:6%) and upon chromatographic purification, the monofluoro derivative was isolated in 40% yield. The use of t-BuOK and Selectfluor in DMF reported for the fluorination of bis(benzenesulfonyl)methane16 resulted in a mixture of 2:3:4 in approximately 1:1:1 ratio. Much better results were obtained when 1 was first subjected to deprotonation using LDA in toluene, followed by electrophilic fluorination with NFSi. This resulted in a mixture of 1, monofluoro and difluoro derivatives in a ratio (%) of 23:69:8, respectively. Since separation of the mono and difluoro derivatives proved to be problematic, 1 was initially separated from the products. The mixture of mono and difluoro derivatives was then oxidized to bissulfones 3 and 4 using H5IO6/catalytic CrO317. At this stage, 3 could be easily separated from the difluoro byproduct 4, to give the monofluoro bis-sulfone 3 in 49% yield (over two steps). With the desired reagent 3 in hand, condensation reactions with carbonyl compounds were tested. The use of Julia reaction for the synthesis of acrylates18 and -fluoro acrylates12b,13b under mild, DBU mediated conditions, has been reported. Aldehydes were therefore subjected to condensation reactions under similar mild conditions. In a typical experiment, aldehyde (1 molar equiv) and bis-sulfone 3 (1.3 molar equiv) were dissolved in freshly distilled CH2Cl2 at room temperature, and DBU (1.5 or 4.0 molar equiv, entry 1, Table 1) in CH2Cl2 was added to the reaction mixture. The progress of the reaction was monitored by tlc for the disappearance of the aldehyde and the reactions were typically complete within 35-120 minutes. The reaction mixtures were partially concentrated and then directly loaded onto a dry silica gel column. The combined E/Z product mixture was eluted and the E/Z ratio was analyzed by 19F NMR spectroscopy. In the case of alkanals that could potentially lead to volatile products, an internal standard was added to the E/Z fluoroalkene mixtures eluted from the column, and the yield was assessed by 19F NMR, prior to complete solvent removal. The yields and stereochemical outcomes of the reactions are shown in Table 1 and comparison to some alternative synthetic routes in the literature is included. All aldehydes tested gave high to excellent yields of fluorovinyl sulfones. The use of 4.0 molar equiv of DBU instead of 1.5 molar equiv did not change the yield or E/Z ratio (entry 1). It should also be noted that the E/Z ratio did not change significantly upon purification of the products, except in the case of 13 (entry 9, unstable product, E/Z ratio 22:78 after purification). In all cases studied, the major isomer formed was Z. The observed stereoselectivities in these cases can be rationalized on the same principles as described in our synthesis of fluoroacrylates.13b The stereochemical outcome in reactions with aldehydes using our methodology is complementary to other known methods, where the major or exclusive isomer formed was E.3,7,19 In the case of aromatic aldehydes stereoselectivity decreased with the bulk of the aldehyde (entries 6, 8), however branching of the aldehyde did not appear to have any influence on the E/Z ratio in the case of aliphatic aldehydes (entries 10-12). Since MgBr2 has been shown to alter the E/Z ratio,12b,20 some experiments were conducted in its presence.21 Wherever tested, these data are also presented in Table 1. In the case of aromatic aldehydes, stereoselectivity depended on the aldehyde: it decreased for 4nitrobenzaldehyde (entry 3), remained the same for thiophene-2-carboxaldehyde (entry 7), and improved for 2-methoxybenzaldehyde (entry 6). A substantial improvement in stereoselectivity was observed for octanal (entry 10). Similar (entry 3) or somewhat better yields (entries 6, 7, 10) were obtained in the presence of MgBr2.

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We were further interested in the reactivity of bis-sulfone 3 with ethyl 2-formyl-1cyclopropanecarboxylate, in order to assess the applicability of the method to the synthesis of fluorinated compounds with the pyrethrin structural motif,22 that are of interest in agricultural chemistry. Since the commercial cyclopropyl carboxaldehyde was a mixture of trans and cis isomers in a 9:1 ratio, four isomeric products were expected and were formed in the reaction. These were isolated in 80% yield by column chromatography (SiO2,CH2Cl2). For characterization purposes the isomers from one reaction were partially separated by preparative tlc (SiO2, 25% EtOAc in hexanes) to give Z-trans, Z-cis and a mixture of E-trans and E-cis isomers. Products formed in the reaction and their ratios, along with chemical shifts of the vinylic F and H atoms, that are most diagnostic in isomer assignments, are shown in Scheme 2. As a test substrate for reactivity of ketones, N-benzylpiperidone was subjected to olefination. Under the conditions used for olefination of aldehydes (DBU, CH2Cl2), a sluggish reaction was observed, with 47% conversion after 24 h. Upon changing the reaction solvent to THF, the reaction was complete in 6 h and the condensation product was isolated in 65% yield.23 A comparable 70% yield was obtained in the reaction of N-benzylpiperidone (1 molar equiv) with 3 (2.4 molar equiv) in the presence of LHMDS (2.4 molar equiv, 0 C), after standard aqueous workup and purification by chromatography. On the other hand, olefination of acetophenone and 1-indanone with 3 in the presence of LHMDS was inefficient. No further attempts were made to optimize reactivity of ketones with 3 at this time. We were curious to compare the reactivity of the Horner-Wadsworth-Emmons (HWE) reagent to that of the bissulfone 3 for the synthesis of fluorovinyl sulfones under these mild condensation conditions, using DBU. For this, reactions of 2-naphthaldehyde and 1-octanal were chosen. Indeed, PhSO2CHFP(O)(OEt)2 (1.3 molar equiv) underwent reaction with 2naphthaldehyde (1 molar equiv) in the presence of DBU (4.0 molar equiv) in CH2Cl2 at rt to give the condensation products in 80% yield and a 40:60 E/Z ratio. Reaction with 1-octanal (1.5 molar equiv of DBU) resulted in 48:52 E/Z product mixture in 65% yield. In this comparison substantially higher stereoselectivities were obtained in condensation reactions of 3 with 2-naphthaldehyde (Table 1, entry 1, 4.0 molar equiv of DBU, 17:83 E/Z) and 1-octanal (Table 1, entry 10, 22:78 E/Z). Finally, in order to compare the reactivity of 3 and PhSO2CHFP (O)(OEt)2, a reaction of each with 2-naphthaldehyde was monitored by 19F NMR in the presence of octafluoronaphthalene as an internal standard. Reaction of 3 (1.3 molar equiv) with 2-naphthaldehyde (1 molar equiv) in the presence of DBU (1.5 molar equiv) showed 60% conversion to products after 15 min. In contrast, in the reaction of the HWE reagent under identical conditions, only about 8% conversion to products occurred in 15 min, indicating a higher reactivity of 3 under these mild condensation conditions. We then assessed the influence of fluorine atom substitution on the reactivity of the bis-sulfone reagent. For this a competitive experiment was conducted, where the unfluorinated bis-sulfone 2 (1.3 molar equiv) and its fluorinated analog 3 (1.3 molar equiv) were allowed to react with 2-naphthaldehyde (1 molar equiv) in CH2Cl2 using DBU (1.5 molar equiv). After 120 min, the reaction was diluted with CH2Cl2 and washed with aqueous NH4Cl. The organic layer was washed with water, dried with anhydrous Na2SO4 and analyzed by tlc (SiO2, 15% EtOAc in hexanes) and by 1H NMR. The only product obtained was fluorinated alkene 5. This was also confirmed by comparison to the independently synthesized 1-phenylsulfonyl-2-(2-naphthyl) ethene (Scheme 3). In summary, we have developed an efficient synthesis of a novel benzothiazolyl based bissulfone reagent for the preparation of fluorovinyl phenyl sulfones via a one-pot Julia olefination. Condensation reactions with aldehydes are high yielding and proceed under mild conditions to give fluoroolefins with moderate to good Z-selectivity. The bis-sulfone reagent

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also showed a greater reactivity as compared to the HWE reagent PhSO2CHFP(O)(OEt)2. As originally reported by us in the synthesis of -fluoro acrylates,13b in this case as well fluorine substitution increases the reactivity of the bis-sulfone reagent.

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Synthesis of (1,3-Benzothiazol-2-ylsulfanyl)methyl Phenyl Sulfone (1)

A solution of iodomethyl phenyl sulfone (3.00 g, 10.6 mmol, 1 molar equiv) and the sodium salt of 2-mercapto-1,3-benzothiazole (6.04 g, 31.9 mmol, 3 molar equiv) in DMF (90.0 mL) was heated at 70 C for 18 h. The reaction mixture was cooled to rt, diluted with water and extracted three times with EtOAc (300 mL). The organic layer was thoroughly washed with water, aqueous NaOH (1M), water, aqueous NH4Cl and finally with brine, and dried over anhydrous Na2SO4. The solvent was evaporated under reduced pressure and the crude product was purified by column chromatography (SiO2, 0.1% acetone in CH2Cl2) to give 2.82 g (83%) of 1 as an ivory solid. 1H NMR (500 MHz, CDCl3): 7.96 (d, 2H, Ar-H, J = 7.5), 7.72 (d, 1H, Ar-H, J = 7.9), 7.68 (d, 1H, Ar-H, J = 7.9), 7.42-7.32 (m, 4H, Ar-H), 7.30 (t, 1H, Ar-H, J = 7.9), 5.03 (s, 2H, CH2). 13C NMR (125 MHz, CDCl3): 161.5, 151.9, 137.0, 135.5, 133.9, 129.2, 128.7, 126.2, 124.9, 121.8, 121.0, 54.9. HRMS calcd. for C14H11NO2S3Na (M+ + Na) 343.9844, found 343.9837.

Synthesis of (1,3-Benzothiazol-2-ylsulfonyl)fluoromethyl Phenyl Sulfone (3)

Step 1 Fluorination. A stirring solution of (1,3-benzothiazol-2-ylsulfanyl)methyl phenyl sulfone 1 (2.00 g, 6.22 mmol, 1 molar equiv) in dry toluene (95 mL), was cooled to -80 C (dry-ice/isoPrOH) under nitrogen gas. LDA (3.58 mL, 7.16 mmol, 1.15 molar equiv of a 2.0 M solution in heptane/THF/EtPh) was added to the reaction mixture with stirring. After 15 min solid NFSi (2.45 g, 7.79 mmol, 1.25 molar equiv) was added. The mixture was allowed to stir at -80 C for 50 min, then warmed to rt and the stirring was continued for an additional 50 min. Sat aq NH4Cl (80 mL) was added to the mixture and the layers were separated. The aqueous layer was extracted three times with EtOAc (200 mL), and the combined organic layer was washed with water, sat aq NaHCO3 and brine. The organic layer was dried over Na2SO4 and the solvent was evaporated under reduced pressure. The 1H and 19F NMR spectra of the crude reaction mixture showed the presence of 1, monofluoro and difluoro derivatives in a ratio of 23%:69%: 8%, respectively. Purification by column chromatography (SiO2, CH2Cl2) afforded 1.55 g of a mixture of mono and difluoro derivatives that were subjected to oxidation. Step 2 Oxidation. To a solution of H5IO6 (4.68 g, 20.5 mmol) in CH3CN (100 mL), CrO3 (22.8 mg, 0.228 mmol) was added, and after stirring at rt for 5 min, a solution of the mono and difluoro derivatives (1.55 g, obtained in step 1) in CH3CN (15.0 mL) was added. The reaction mixture was allowed to stir at rt for 39 h and the conversion was checked by 19F NMR and tlc (SiO2, CH2Cl2). Since a small amount of unoxidized difluoro derivative was still present, 0.520 mg (2.28 mmol) of H5IO6 was added, and the reaction was allowed to proceed for another 5 h, when 19F NMR and tlc showed complete conversion of the monosulfones to the bissulfones. The reaction mixture was filtered and the solid residue was washed with CH3CN. The filtrate was concentrated under reduced pressure, water was added and the mixture was extracted with EtOAc (3x). The combined EtOAc layers were thoroughly washed with water and finally with brine, and dried over anhydrous Na2SO4. The crude product mixture was separated by column chromatography (SiO2, CH2Cl2) to give 1.13 g (49% yield over two steps) of 3 as a white solid. 1H NMR (500 MHz, CDCl3): 8.27 (br d, 1H, Ar-H, J = 8.3), 8.07 (d, 2H, Ar-H, J = 7.4), 8.04 (br d, 1H, Ar-H, J = 8.3), 7.80 (br t, 1H, Ar-H, J = 7.6), 7.71-7.63 (m, 4H, Ar-H), 6.37 (d, 1H, 2JFH = 45.6). 13C NMR (125 MHz, CDCl3): 161.7, 152.6, 137.6, 136.0, 134.8,

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130.5, 129.5, 129.0, 128.2, 126.1, 122.4, 105.0 (d, 1JCF = 268.2). 19F NMR (470 MHz): -169.95 (d, 2JFH = 45.8). HRMS calcd. for C14H10FNO4S3Na (M+ + Na) 393.9648, found 393.9643.

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Condensation of 4-Chlorobenzaldehyde with 3

To a stirring solution of 4-chlorobenzaldehyde (100 mg, 0.711 mmol, 1 molar equiv) and 3 (344 mg, 0.926 mmol, 1.3 molar equiv) in freshly distilled CH2Cl2 (4.4 mL) was added DBU (163 mg, 1.07 mmol, 1.5 molar equiv) in CH2Cl2 (4.4 mL) at rt. Upon addition of DBU, the reaction mixture immediately turned yellow. The stirring was continued at rt until complete consumption of the aldehyde was observed by tlc (SiO2, CH2Cl2, 70 min). The reaction mixture was directly loaded onto a dry silica gel column (200-300 mesh) and the product 8 was eluted with CH2Cl2 as an E/Z mixture. Upon removal of solvent under reduced pressure, 187 mg (89%) of 8 was isolated and E/Z ratio was determined by 19F NMR (Table 1, entry 4). HRMS calcd. for C14H10ClFO2SNa (M+ + Na) 318.9966, found 318.9960. For 1H NMR analysis, a small amount of the E and Z-isomers was separated by tlc (SiO2, 20% acetone in hexane). Eisomer: 1H NMR (500 MHz, CDCl3): 8.01 (d, 2H, Ar-H, J = 7.8), 7.71 (t, 1H, Ar-H, J = 7.7), 7.61 (t, 2H, Ar-H, J = 7.8), 7.51 (d, 2H, Ar-H, J = 8.7), 7.37 (d, 2H, Ar-H, J = 8.7), 7.02 (d, 1H, 2JFH = 34.5). Z-isomer: 1H NMR (500 MHz, CDCl3): 7.88 (d, 2H, Ar-H, J = 7.8), 7.69 (t, 1H, Ar-H, J = 7.4), 7.56 (t, 2H, Ar-H, J = 7.6), 7.38 (ABq, 4H, Ar-H, J = 8.5), 6.84 (d, 1H, 2JFH = 21.2).

Acknowledgments
This work was supported by NSF Grant CHE-0516557, infrastructural support and support for A.K.G. were provided by NIH RCMI Grant 5G12 RR03060. Support of M.H. through the Bristol-Myers Squibb summer undergraduate research program is gratefully acknowledged. Acquisition of a mass spectrometer was funded by NSF Grant CHE-0520963. We thank Dr. Andrew Poss (Honeywell) for a sample of NFSi, Dr. G. Sankar Lal (Air Products) for a sample of Selectfluor and Dr. Padmanava Pradhan (NMR facility manager) for assistance with the 2D NMR experiments.

References
(2). Njera C, Yus M. Tetrahedron 1999;55:1054710658. (3). (a) Inbasekaran M, Peet NP, McCarthy JR, LeTourneau ME. J. Chem. Soc., Chem. Commun 1985:678679. (b) Koizumi T, Hagi T, Horie Y, Takeuchi Y. Chem. Pharm. Bull 1987;35:3959 3962. (c) McCarthy JR, Matthews DP, Edwards ML, Stemerick DM, Jarvi ET. Tetrahedron Lett 1990;31:54495452. (4). (a) McCarthy JR, Matthews DP, Stemerick DM, Huber EW, Bey P, Lippert BJ, Snyder RD, Sunkara PS. J. Am. Chem. Soc 1991;113:74397440. (b) McCarthy JR, Huber EW, Le T-B, Laskovics FM, Matthews DP. Tetrahedron 1996;52:4558. (c) Berkowitz DB, de la Salud-Bea R, Jahng W-J. Org. Lett 2004;6:18211824. [PubMed: 15151423] (5). Wnuk SF, Garcia PI Jr. Wang Z. Org. Lett 2004;6:20472049. [PubMed: 15176815] (6). Uno H, Sakamoto K, Tominaga T, Ono N. Bull. Chem. Soc. Jpn 1994;67:14411448. (7). Asakura N, Usuki Y, Iio H. J. Fluorine Chem 2003;124:8188. (8). Nakamura T, Guha SK, Ohta Y, Abe D, Ukaji Y, Inomata K. Bull. Chem. Soc. Jpn 2002;75:2031 2041. (9). Kunugi A, Yamane K, Yasuzawa M, Matsui H, Uno H, Sakamoto K. Electrochim. Acta 1993;38:10371041. (10). Prakash, GKS.; Chacko, S.; Olah, GA. Abstracts of Papers. 234th National Meeting of the American Chemical Society; Boston, MA. Washington, DC: American Chemical Society; 2007. ORGN 846 (11). (a) Blakemore PR. J. Chem. Soc., Perkin Trans 2002;1:25632585. (b) Plesniak K, Zarecki A, Wicha J. Top. Curr. Chem 2007;275:163250.

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(12). (a) Chevrie D, Lequeux T, Demoute JP, Pazenok S. Tetrahedron Lett 2003;44:81278130. (b) Pfund E, Lebargy C, Rouden J, Lequeux T. J. Org. Chem 2007;72:78717877. [PubMed: 17880136] (13). (a) Ghosh AK, Zajc B. Org. Lett 2006;8:15531556. [PubMed: 16597108] (b) Zajc B, Kake S. Org. Lett 2006;8:44574460. [PubMed: 16986924] (14). Bordwell FG, Clemens AH, Smith DE, Begemann J. J. Org. Chem 1985;50:11511156. (15). Ono K, Yoshida A, Saito N, Fujishima T, Honzawa S, Suhara Y, Kishimoto S, Sugiura T, Waku K, Takayama H, Kittaka A. J. Org. Chem 2003;68:74077415. [PubMed: 12968893] (16). Ni C, Li Y, Hu J. J. Org. Chem 2006;71:68296833. [PubMed: 16930033] (17). Xu L, Cheng J, Trudell ML. J. Org. Chem 2003;68:53885391. [PubMed: 12816505] (18). Blakemore PR, Ho DKH, Nap WM. Org. Biomol. Chem 2005;3:13651368. [PubMed: 15827628] (19). Andrei D, Wnuk SF. J. Org. Chem 2006;71:405408. [PubMed: 16388671] (20). Lebrun M-E, Le Marquand P, Berthelette C. J. Org. Chem 2006;71:20092013. [PubMed: 16496987] (21). In a typical experiment, to a mixture of aldehyde (1 molar equiv), bis-sulfone 3 (1.3 molar equiv) and anhydrous MgBr2 (1.8 molar equiv) in anhydrous THF (5 mL per mmol of aldehyde), a solution of DBU (3.9 molar equiv) in anhydrous THF (5 mL per mmol of aldehyde) was added. The mixture was stirred at room temperature, until the disappearance of the aldehyde was observed by tlc. Aqueous NH4Cl was added and the mixture was extracted with ethyl acetate (3x). The organic layer was washed with water and brine, dried over anhydrous Na2SO4 and the solvent was evaporated. (22). (a) Jeschke P. ChemBioChem 2004;5:570589. (b) Liu W, Qin S, Gan J. J. Agric. Food Chem 2005;53:38143820. [PubMed: 15884802] (23). Conditions as reported in ref. 12b were used (N-benzylpiperidone: 1.2 mol equiv; 3: 1 mol equiv; DBU: 1.4 mol equiv; THF: 5 mL per mmol of 3; r.t., 6 h).

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Scheme 1.

Synthesis of the fluorinated bis-sulfone.

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Scheme 2.

Condensation of 3 with ethyl 2-formyl-1-cyclopropane carboxylate.

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Scheme 3.

Comparative reactivity of 2 and 3 with 2-naphthaldehyde.

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Table 1

Mild synthesis of (-fluoro)vinyl sulfones via the Julia olefination .

EntryAldehyde

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Time (min)aProducts 5-1 Yield,bE/Z ratioc (lit)d

120

5: 94%, 16:8

Using 4.0 mo equiv of DBU 93%, 17:83 2 80

6: 90%, 16:8

(85%, 95:5), 19 (52%, 77:23),ref 7 (85%, E only 3b (67%, E o

ref 3a

90

7: 85%, 22:7

With MgBr2 84%, 29:71 ( 93:7)ref 3b 4 70

8: 89%, 17:8

(85%, 81:19) 3c (80%, E o

ref 3a

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EntryAldehyde

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Time (min)aProducts 5-1 Yield,bE/Z ratioc (lit)d

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90

9: 90%, 12:8

(81%, 98:2)r

120

10: 75%, 48:

With MgBr2 91%, 36:64

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EntryAldehyde

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Time (min)aProducts 5-1 Yield,bE/Z ratioc (lit)d

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90

11: 82%, 11:

With MgBr2 96%, 9:91 8 80

12: 72%, 44:

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EntryAldehyde

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Time (min)aProducts 5-1 Yield,bE/Z ratioc (lit)d

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40

13:f 87%, 13

(72%, E only

3b

10

90

14: 85% (91% 22:78

With MgBr2 95%, 4:96 (4 83:17)ref 7 11 35

15: 66%, 23:

(90%, 68:32) 19 (52%, 90

ref 7
12 90

16: 59% (71% 23:77

a b

Time at isolation. Yields of isolated, purified products (reactions were performed under similar conditions but were not optimized for individual cases).

c Relative ratio of isomers determined by 19F NMR of the crude reaction mixture. d Where applicable, literature data and references are provided for comparison.

e Referenced to CFCl3 as internal standard.

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f The product is unstable and undergoes decomposition. g

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Yield determined by addition of internal standard octafluoronaphthalene to the E/Z mixture eluted from the column, prior to complete solvent evaporation.

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