Unexpected results in the reaction of active methylenecompounds with phenylsulfonyl-1,2-propadiene

triggered by triphenylphosphine

Cheng Lu and Xiyan Lu*

State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu,

Shanghai, 200032, China

Received 6 April 2004; revised 27 May 2004; accepted 2 June 2004

Abstract—Some unexpected phenomena were observed in the reaction of active methylene compounds with phenylsulfonyl-1,2-propadienein the presence of Ph3P. The reaction gave three types of products: Michael adducts, rearranged adducts or a three-component adduct. It couldbe explained as an interesting phosphine-triggered, sulfinate anion-catalyzed reaction.q 2004 Elsevier Ltd. All rights reserved.

1. Introduction

A number of reports on organocatalytic transformationshave appeared covering a wide range of reactions. Amongthem, some important reactions were discovered in thephosphine-catalyzed reaction of 2,3-butadienoates or2-butynoates,1 such as isomerization,2 a-addition,3

g-addition,4 and [3þ2]-cycloaddition.5 Recently, wereported the phosphine-catalyzed tandem reactions ofelectron-deficient allenes (allenoates, allenones) or alkynes(alkynoates, alkynones) with various types of bifunctionalnucleophiles, which offer an efficient route to constructheterocycles under mild conditions with high efficiency(Scheme 1).6

Based on the phosphine-catalyzed tandem reactions, more

efforts were made to investigate the reactions of otherelectron-deficient allenes. However, some unexpectedresults were obtained when phenylsulfonyl-1,2-propadienewere used. Herein we wish to report the unexpected resultsobtained from the reactions of active methylene compoundswith phenylsulfonyl-1,2-propadiene.

2. Results and discussions

Heating a mixture of 1,3-cyclohexanedione and phenyl-sulfonyl-1,2-propadiene in toluene in the presence of acatalytic amount of Ph3P gave 49% yield of the adduct 3, notthe expected cyclized product 2 formed from tandemnucleophilic additions (Scheme 2).6

Reaction of acetylacetone with phenylsulfonyl-1,2-propa-diene was similar to that of the 1,3-cyclohexanedione(Scheme 3).

0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.doi:10.1016/j.tet.2004.06.081

Tetrahedron 60 (2004) 6575–6579

Scheme 1. Scheme 2.

* Corresponding author. Tel.: þ86-21-64163300; fax: þ86-21-64166128;e-mail address: xylu@mail.sioc.ac.cn

Keywords: Phosphine; Active methylene compounds; Allenic sulfone;Sulfinate.

The unexpected results urged us to make further investi-gation on the reactions. To our surprise, another type ofproduct was obtained when other active methylenecompounds were used instead of cyclohexane-1,3-dione oracetylacetone (Scheme 4).

Reaction of ethyl acetoacetate, diethyl malonate or ethylcyanoacetate with phenylsulfonyl-1,2-propadiene gaverearranged adducts in which the sulfonyl group migratedfrom the terminal carbon atom of the allenic sulfone to thecentral carbon atom. An independent synthesis of 5 from thereaction of 3-bromo-2-phenylsulfonylpropene (8) with ethylacetoacetate in the presence of a base comfirmed thesulfonyl-migrated structure (Scheme 5).

Reaction of malononitrile with phenylsulfonyl-1,2-propa-diene afforded an enamine derivative (9), a three-component adduct (Scheme 6).7 The sulfonyl group in theproduct also migrated. It is quite difficult to explain thesephenomena provided that Ph3P is the catalyst, becauseumpolung adduct should be formed according to ourexperience in the related work.1a,3,4

Then, we turned our attention to the chemistry of allenicsulfones. Padwa’s work on the sulfinate anion-mediated

reaction of allenic sulfones8 inspired us to understand moreabout the abnormal phenomena we observed. We wonderthat the reaction of active methylene compounds withphenylsulfonyl-1,2-propadiene is possibly triggered byPPh3 and mediated by sulfinate anion.

To test the possibility of the sulfinate anion mediatedformation of the abnormal product, a mixture of ethylacetoacetate, phenylsulfonyl-1,2-propadiene and PhSO2Nawas heated in toluene, and indeed the rearranged product 5was obtained in 23% yield (Scheme 7). No reactionoccurred in the absence of PhSO2Na.

Since no sulfinates were added in the reaction discussedbefore, we were puzzled by the origin of the sulfinate anion.Although the detailed mechanism is still unclear, weproposed that it was generated in situ as illustrated inScheme 8.

Nucleophilic addition of triphenylphosphine to phenyl-sulfonyl-1,2-propadiene forms a zwitterionic intermediate,the carbanion center of which would deprotonate the acidicproton of the active methylene compound to effect furtherconjugate addition of the carbonucleophile to the vinylphosphonium salt9 and simultaneous release of the sulfinateanion.

It is reasonable that the above process is favored by thepresence of a good releasing group (sulfonyl group). If thesulfonyl group was replaced by an ester or acyl group thatare not good releasing groups, this process was not likely to

Scheme 3.

Scheme 4.

Scheme 5.

Scheme 6.

Scheme 7.

Scheme 8.

C. Lu, X. Lu / Tetrahedron 60 (2004) 6575–65796576

happen. In this case, an alternative pathway would bepossible, from which the umpolung product can be formed(Scheme 9). This could partly explain why allenic sulfonesshow a completely different reaction behavior from thecorresponding allenoates or allenones towards activemethylene compounds in the presence of tertiaryphosphines.

The sulfinate anion generated as described above can furthercatalyze the reactions of active methylene compounds withphenylsulfonyl-1,2-propadiene and the results can beclassified into three types:

(1) For the reaction of those active methylene compoundswith relatively higher kinetic acidity (1,3-cyclo-hexanedione or acetylacetone), the sulfinate anionsimply served as a base to promote the normal Michaeladdition reaction (Scheme 10).

(2) For the reaction of those active methylene compoundswith relatively low kinetic acidity, the competitionbetween the sulfinate anion and the carbanion of theactive methylene compounds will occur. In this case,the sulfinate ion served as a nucleophilic catalyst topromote the formation of the rearranged product(Scheme 11). The sulfinate anion attacks the centralcarbon of the allene to initiate the reaction and thecatalytic cycle is completed by the release of anothersulfinate anion from the terminal carbon to give thesulfonyl group-migrated product.

(3) For the reaction of malononitrile with phenylsulfonyl-1,2-propadiene, the sulfinate anion also served as anucleophilic catalyst. The reaction intermediate wasfurther captured by a second molecule of malononitrileand effected intramolecular cyclization reaction toform a six-member enamine derivative (Scheme 12).

In summary, we have found that the reaction of activemethylene compounds with phenylsulfonyl-1,2-propadienecould be interestingly triggered by triphenylphosphine and

catalyzed by the in situ generated sulfinate anion to givethree types of adducts: Michael adducts, rearranged adductsor a three-component adduct.

3. Experimental

3.1. General

Phenylsulfonyl-1,2-propadiene (1)10 and 3-bromo-2-phenylsulfonylpropene (8)11 were prepared by the methodsdescribed in the literature.

3.1.1. Reaction of 1,3-cyclohexanedione with phenyl-sulfonyl-1,2-propadiene (1) in the presence of Ph3P. To astirred solution of 1,3-cyclohexanedione (56 mg, 0.5 mmol)and Ph3P (6.5 mg, 0.025 mol) in toluene (1.5 mL) at 80 8C

Scheme 9.

Scheme 10.

Scheme 11.

Scheme 12.

C. Lu, X. Lu / Tetrahedron 60 (2004) 6575–6579 6577

under nitrogen was added a solution of phenylsulfonyl-1,2-propadiene (1, 90 mg, 0.5 mmol) in toluene (1 mL). Thesolution was stirred for another 9 h. The solvent wasremoved under reduced pressure and the residue waspurified by flash chromatography on silica gel (eluents:ethyl acetate/petroleum ether) to give 3 as an oil (72 mg,49%). Oil. IR (KBr): n 2951, 1656, 1612, 1323, 1311, 1172,1136 cm21. 1H NMR (300 MHz, CDCl3): d 7.92 (d,J¼8.5 Hz, 2H), 7.70–7.67 (m, 1H), 7.61–7.56 (m, 2H),5,35 (s, 1H), 5.00 (d, J¼1.5 Hz, 1H), 4.96 (d, J¼1.5 Hz,1H), 3.95 (s, 2H), 2.32 (t, J¼6.7 Hz, 2H), 2.24 (t, J¼6.5 Hz,2H), 1.98–1.92 (m, 2H). 13C NMR (75 MHz, CDCl3):199.2, 174.7, 145.5, 138.2, 134.1, 129.2, 128.5, 109.9,106.5, 59.3, 27.7, 20.8. MS (m/z): 292 (Mþ), 217, 151, 84,77, 49 (100), 43. HRMS-EI calcd for C15H16O4S: (Mþ)292.0769. Found: 292.0780.

3.1.2. Reaction of acetylacetone with phenylsulfonyl-1,2-propadiene (1) in the presence of Ph3P. To a stirredsolution of acetylacetone (250 mg, 2.5 mmol) and Ph3P(13.1 mg, 0.05 mol) in toluene (1.5 mL) at room tempera-ture under nitrogen was added a solution of 1 (90 mg,0.5 mmol) in toluene (1 mL) by a syringe over 5 h. Thesolvent was removed under reduced pressure and the residuewas purified by flash chromatography on silica gel (eluents:ethyl acetate/petroleum ether) to give 4 as a solid (75 mg,54%). Mp 102–104 8C. IR (neat): n 2750, 1600, 1447, 1170,954 cm21. 1H NMR (300 MHz, CDCl3): d 16.75 (s, 1H),7.94 (d, J¼7.3 Hz, 2H), 7.94 (d, J¼7.3 Hz, 2H), 7.68 (d,J¼7.3 Hz, 1H), 7.60 (t, J¼7.3 Hz, 2H), 6.43 (s, 1H), 5.62 (s,1H), 3.18 (s, 2H), 1.85 (s, 6H). (1H NMR showstrace amount of the corresponding diketone tautomer). 13CNMR (75 MHz, CDCl3): 191.9, 149.1, 138.1, 133.8,129.3, 128.2, 128.1, 123.3, 104.3, 29.8, 27.7, 22.4. MS(m/z): 280 (Mþ), 139 (100), 138, 123, 96, 95, 43. Anal.Calcd for C14H16O4S: C, 59.98; H, 5.75. Found: C, 59.92;H, 5.74.

3.1.3. General procedure for the reaction of activemethylene compounds (ethyl acetoacetate, diethylmalonate or ethyl cyanoacetate) with 1 in the presenceof Ph3P. To a stirred solution of active methylenecompound (2.5 mmol) and Ph3P (13.1 mg, 0.05 mol) intoluene (1.5 mL) at room temperature under nitrogen wasadded a solution of 1 (90 mg, 0.5 mmol) in toluene (1 mL)by a syringe over 5 h. The solvent was removed underreduced pressure and the residue was purified by flashchromatography on silica gel (eluents: ethyl acetate/petroleum ether) to give the rearranged product as oil.

3.1.4. Ethyl 2-acetyl-4-phenylsulfonyl-pent-4-enoate (5).Yield (50%). Oil. IR (neat): n 2986, 1742, 1718, 1307, 1148,1127, 750, 690 cm21. 1H NMR (300 MHz, CDCl3): d 7.87(d, J¼8.2 Hz, 2H), 7.65 (t, J¼7.7 Hz, 1H), 7.56 (dd, J¼7.7,8.2 Hz, 2H), 6.38 (s, 1H), 5.83 (s, 1H), 4.17 (q, J¼7.1 Hz,2H), 4.03 (t, J¼7.1 Hz, 1H), 2.76 (dq, J¼7.1 Hz, 15.5 Hz,2H), 2.36 (s, 3H), 1.25 (t, J¼7.1 Hz, 3H). (1H NMR showsthe presence of the corresponding enol tautomer: 12.87 (s,1H), 7.87 (d, J¼8.2 Hz, 2H), 7.65 (t, J¼7.7 Hz, 1H), 7.56(dd, J¼7.7, 8.2 Hz, 2H), 5.60 (s, 1H), 3.96 (q, J¼7.1 Hz,2H), 3.15 (s, 2H), 1.02 (t, J¼7.1 Hz, 3H). 13C NMR(75 MHz, CDCl3): 201.3, 168.1, 146.7, 138.1, 133.7, 129.3,129.0, 128.1, 128.0, 127.0, 61.7, 57.4, 29.8, 27.9, 13.9. MS

(m/z): 310 (Mþ), 265, 169, 126, 125, 97, 77, 43 (100). Anal.Calcd for C15H18O5S: C, 58.05; H, 5.85. Found: C, 58.19;H, 5.81.

3.1.5. Diethyl 2-(20phenylsulfonylallyl)malonate (6).Yield (43%). Oil. IR (neat): n 2895, 1733, 1718, 1448,1307, 1138, 1136, 751, 690 cm21. 1H NMR (300 MHz,CDCl3): d 7.89 (d, J¼7.6 Hz, 2H), 7.64 (t, J¼7.6 Hz, 1H),7.56 (t, J¼7.6 Hz, 2H), 6.42 (s, 1H), 5.85 (s, 1H), 4.16 (q,J¼7.1 Hz, 4H), 3.76 (t, J¼7.5 Hz, 1H), 2.85 (d, J¼7.5 Hz,2H), 1.13 (t, J¼7.1 Hz, 6H). 13C NMR (75 MHz, CDCl3):168.0, 146.7, 138.2, 133.7, 129.3, 128.2, 126.4, 61.7, 50.3,28.8, 13.9. MS (m/z) 295 (Mþ2OEt), 249, 199, 171, 143,125 (100), 97. Anal. Calcd for C16H20O6S: C, 56.46; H,5.92. Found: C, 56.69; H, 6.17.

3.1.6. Ethyl 4-phenylsulfonyl-2-cyanopent-4-enoate (7).Yield (42%). Oil. IR (neat): n 2987, 2254, 1747, 1718, 1448,1138, 749, 690 cm21. 1H NMR (300 MHz, CDCl3): d 7.90(d, J¼7.6 Hz, 2H), 7.68 (t, J¼7.6 Hz, 1H), 7.60 (t,J¼7.6 Hz, 2H), 6.52 (d, J¼1.2 Hz, 1H), 6.05 (d,J¼1.2 Hz, 1H), 4.28 (q, J¼7.1 Hz, 2H), 4.02 (dd, J¼5.7,9.5 Hz, 1H), 2.97 (dd, J¼5.7 Hz, 15.6 Hz, 1H), 2.73 (dd,J¼9.5 Hz, 15.6 Hz, 1H), 1.31 (t, J¼7.1 Hz, 3H). 13C NMR(75 MHz, CDCl3): 164.6, 144.5, 137.6, 134.1, 129.5, 128.8,128.3, 115.3, 63.3, 36.6, 30.1, 13.9. MS (m/z): 248(Mþ2OEt), 152, 124 (100), 97, 78, 77, 51, 43. Anal.Calcd for C14H15NO4S: C, 57.32; H, 5.15; N, 4.77. Found:C, 57.00; H, 5.40; N, 4.87.

3.1.7. Synthesis of 5 from the reaction of 3-bromo-2-phenylpropene with ethyl acetoacetate. To a stirredsolution of 3-bromo-2-phenylpropene (2 mmol) in aceto-nitrile (2 mL) at room temperature was added ethylacetoacetate (2 mmol) and potassium carbonate (2 mmol),and the suspension was stirred for 48 h. The solid wasfiltered and the filtrate was subject to reduced pressure toremove the solvent. The residue was purified by flashchromatography on silica gel (eluents: ethyl acetate/petroleum ether) to give 5 as an oil. The 1H NMR of theproduct was identical to that obtained from the reaction ofethyl acetoacetate with phenylsulfonyl-1,2-propadiene inthe presence of Ph3P.

3.1.8. Reaction of malononitrile with 1 in the presence ofPh3P. To a stirred solution of malononitrile (2.5 mmol) andPh3P (13.1 mg, 0.05 mol) in toluene (1.5 mL) at roomtemperature under nitrogen was added a solution of 1(90 mg, 0.5 mmol) in toluene (1 mL) by a syringe over 5 h.The solvent was removed under reduced pressure and theresidue was purified by flash chromatography on silica gel(eluents: ethyl acetate/petroleum ether) to give therearranged product 9 as a solid. Yield (52%). Mp 177–178 8C. IR (neat): n 3437, 3340, 3228, 2213, 1658, 1448,1324, 1152 cm21. 1H NMR (300 MHz, CD3COCD3): d 8.04(d, J¼7.5 Hz, 2H), 7.87 (t, J¼7.5 Hz, 1H), 7.58 (t,J¼7.5 Hz, 2H), 7.37 (weak singlet), 3.75–3.68 (m, 1H),3.26 (dt, J¼13.2, 2.0 Hz, 1H), 2.69 (t, J¼13.2 Hz, 1H), 2.63(d, J¼15.3 Hz, 1H), 2.53 (ddd, J¼15.3, 5.7, 2.0 Hz, 2H).MS (m/z): 312 (Mþ), 170 (100), 143, 124, 117, 105, 77, 51.HRMS-EI calcd for C15H12N4O2S: (Mþ) 312.0681. Found312.0657. The structure of 9 was further confirmed by X-raycrystallography.7

C. Lu, X. Lu / Tetrahedron 60 (2004) 6575–65796578

3.1.9. Reaction of ethyl acetoacetate with 1 in thepresence of sodium benzenesulfinate. In a reaction tubewas charged with sodium benzenesulfinate dihydrate(10 mg, 0.05 mmol). The reaction tube was heated undervacuum to remove the water. A solution of ethylacetoacetate (325 mg, 2.5 mmol) in toluene (1 mL) wasadded under nitrogen. The mixture was heated to 90 8C. Asolution of 1 (90 mg, 0.5 mmol) in toluene (1 mL) wasadded by a syringe over 5 h. After cooling, the solventwas removed under reduced pressure and the residue waspurified by flash chromatography on silica gel (eluents:ethyl acetate/petroleum ether) to give 5 as an oil. The 1HNMR of product was identical to that obtained from thereaction of ethyl acetoacetate with 1 in the presence of Ph3P.

Acknowledgements

We thank the Major State Basic Research Program (GrantG20000077502-A). We also thank the National NaturalSciences Foundation of China (29972048) and ChineseAcademy of Sciences for the financial support.

References and notes

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