DOI: 10.1002/chem.201102430

Unusual Ester-Directed Regiochemical Control in endo-SelectiveAsymmetric 1,3-Dipolar Cycloadditions of Azo ACHTUNGTRENNUNGmethine Ylides with

b-Sulfonyl ACHTUNGTRENNUNGAcrylates

Min-Chao Tong,[a] Jun Li,[a] Hai-Yan Tao,[a] Yu-Xue Li,*[b] and Chun-Jiang Wang*[a, b]

Five-membered nitrogen heterocycles, especially highlysubstituted pyrrolidines, are widely featured in pharmaceuti-cals, natural alkaloids, or organocatalysts and also representuseful building blocks in organic synthesis.[1] During the lastdecade, asymmetric 1,3-dipolar cycloadditions of azome-thine ylides and electron-deficient alkenes have been report-ed to generate stereochemically complex pyrrolidines withmoderate to high enantio- and diastereoselectivities.[2] De-spite excellent results achieved for this transformation, mostdipolarophiles applied in these reactions are mono-activatedor symmetrically double-activated, electron-deficient al-kenes.[3–8] However, unsymmetrically 1,2-disubstituted al-kenes with two different electron-withdrawing groups havebeen seldom studied in the catalytic 1,3-dipolar cycloaddi-tion, probably owing to the synthetic challenges associatedwith the regio-, enantio- and diastereoselectivity. Recently,an excellent result was achieved by Carretero and co-work-ers when employing unsymmetrically 1,2-diactivated (Z)-sul-fonyl acrylate as the dipolarophile and CuI/(R)-Segphoscomplex as the catalyst. Here, the high regioselectivity wasmainly controlled by the sulfonyl group, accompanied byexo-preferred diastereoselectivity[9a] (Scheme 1 left).

Recently, we reported a new family of chiral TF-Bipham-Phos ligands that exhibited high diastereoselectivity andgood to excellent enantioselectivity in the transition-metal-catalyzed asymmetric 1,3-dipolar cycloaddition of azome-thine ylides with various mono-activated and symmetricallydouble-activated, electron-deficient alkenes.[10] Encouragedby these achievements and intense curiosity about the per-formance of unsymmetrically substituted 1,2-diactivated di-polarophiles, herein, we describe that AgI/TF-BiphamPhoscomplexes serve as efficient catalysts for the highly endo-se-lective 1,3-dipolar cycloaddtion of azomethine ylides and

(Z)-sulfonyl acrylate with unusual regioselectivity, which isexclusively controlled by the ester group rather than the sul-fonyl group (Scheme 1 right). Azomethine ylide versatility isone of the key features of the present method: excellent re-activity, selectivity, and structural scope were uniformly ob-served for various azomethine ylides, especially for those de-rived from a-substituted amino acids, with which a uniquequaternary stereogenic center was generated efficiently.

Initially, we began our investigation by testing the reac-tion of (Z)-sulfonyl acrylate 2 and imino ester 3 a withAgOAc/rac-(�)-TF-BiphamPhos (1 a) as the catalyst andEt3N as the base. The reaction was finished in less than30 min at room temperature and delivered a single isomer4 a in 78 % yield with high diastereoselectivity (>98:2,Scheme 2).[11] Surprisingly, the regioselectivity in this case

was controlled by the ester group other than the sulfonylgroup. These conclusions were further confirmed by X-raydiffraction analysis of the enantiomerically pure compound4 j (see below).

Having established the unusual ester-controlled regiose-lectivity and endo selectivity exerted by the AgOAc/rac-(�)-TF-BiphamPhos complex in this cycloaddition reaction, wethen conducted the asymmetric reaction to evaluate the

[a] M.-C. Tong, J. Li, H.-Y. Tao, Prof. Dr. C.-J. WangCollege of Chemistry and Molecular SciencesWuhan University, 430072 (China)Fax: (+86) 27-68754067E-mail : cjwang@whu.edu.cn

[b] Prof. Dr. Y.-X. Li, Prof. Dr. C.-J. WangState Key Laboratory of Organometallic ChemistryShanghai Institute of Organic ChemistryFenglin Road, Shanghai 230032 (China)E-mail : liyuxue@sioc.ac.cn

Supporting information for this article is available on the WWWunder http://dx.doi.org/10.1002/chem.201102430.

Scheme 1. Catalytic asymmetric 1,3-dipolar cycloaddition of unsymmetri-cally 1,2-diactivated sulfonylacrylate with imino esters.

Scheme 2. AgOAc/(�)-TF-BiphamPhos-catalyzed 1,3-dipolar cycloaddi-ton of imino ester 3a with unsymmetrically 1,2-diactivated sulfonylacry-late 2.

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enantioselectivity with chiral TF-BiphamPhos ligand. Al-though both silver(I) and copper(I) salts combined with 1 aefficiently afforded the desired endo-4 a with high regio- anddiastereoselectivity, AgOAc/1 a complex gave a better resultin terms of the enantioselectivity (Table 1, entries 1 and 2).Subsequently, other TF-BiphamPhos ligands were examinedto further improve the enantioselectivity, and the represen-tative results are summarized in Table 1. The catalytic activi-ty of ligands 1 a and 1 b was found to be superior to that ofligands 1 c and 1 d (Table 1, entries 1 and 3–5). These resultsdemonstrated the importance of steric and electronic effectsof the ligands on the enantioselectivity: when the phenylgroup on the phosphorus atom of ligand 1 a was replaced bya more sterically hindered, but electron-withdrawing 3,5-bis(trifluoromethyl)phenyl group, the enantioselectivity de-creased significantly; ligand 1 d containing cyclohexyl groupsalso displayed a detrimental effect. Ligand 1 e, bearing twobromine atoms at the 3,3’-positions of the TF-BiphamPhosbackbone, emerged as the most effective chiral ligand andprovided endo-4 a in high yield and excellent enantioselec-tivity of 96 % (Table 1, entry 6). A subsequent survey of sol-vent effects indicated that EtOAc was the solvent of choicein terms of the reactivity and enantioselectivity (Table 1, en-tries 6–8).

Under the optimized reaction conditions, the scope andlimitations of this 1,3-dipolar cycloaddition were investigat-

ed, and the results are summarized in Table 2. A wide arrayof glycinate-derived imino esters 2 stemming from aromaticaldehydes bearing electron-deficient (Table 2, entries 1–5),electron-neutral (Table 2, entry 6), and electron-rich sub-stituents (Table 2, entries 7–10) on the aryl ring all per-formed well, providing the corresponding endo products inhigh yields (62–85%), exclusive regioselectivity, excellentdiastereoselectivities (>98:2 d.r.) and enantioselectivities(96–99 % ee). The substitution pattern of the arene only hadlittle effect on the reactivity and selectivity of the reaction;ortho-substituted imino esters 3 e and 3 h underwent thistransformation smoothly, leading to the corresponding endoadducts 4 e and 4 h with 96 and 97 % ee, respectively(Table 2, entries 5 and 8). Naphthyl aldehyde-derived iminoester 3 k could also be successfully applied in this reactionand a high yield (83 %) and excellent enantioselectivity(99 %) were obtained (Table 2, entry 11). The current cata-lytic system was efficient for the heteroaromatic 2-furyl and2-thienyl imino esters 3 l and 3 m, which delivered the de-sired adducts with 96 and 99 % ee, respectively (Table 2, en-tries 12 and 13). However, no cycloaddition occurred whenalkyl- or alkenyl-substituted imino esters were tested underthe optimal reaction conditions (Table 2, entries 14 and 15).

Compared with the literature results,[9a] one of the keyfeatures of this ester-controlled and endo-selective 1,3-dipo-lar cycloaddition is that high yields and excellent selectivi-ties were uniformly observed for the imino esters derivedfrom a-substituted amino acids, such as (�)-alanine, (�)-leu-cine, (�)-2-aminobutyric acid, and (�)-phenylalanine, af-fording the highly substituted pyrrolidines bearing a uniquenitrogen-substituted quaternary stereogenic center.[12]

Table 1. Screening studies on the catalytic asymmetric 1,3-dipolar cyclo-addition of sulfonylacrylate 2 a with imino ester 3a.[a]

Entry Ligand [M] Solvent Time[min]

Yield[b]

[%]ee[c]

[%]

1 (S)-1a AgOAc CH2Cl2 30 76 872 (S)-1a [CuACHTUNGTRENNUNG(MeCN)4BF4] CH2Cl2 30 76 833 (S)-1b AgOAc CH2Cl2 30 72 884 (S)-1c AgOAc CH2Cl2 30 73 635 (S)-1d AgOAc CH2Cl2 30 70 806 (R)-1e AgOAc CH2Cl2 30 80 967 (R)-1e AgOAc toluene 30 78 978 (R)-1e AgOAc EtOAc 30 82 999 (S)-1e AgOAc EtOAc 30 80 98

[a] All reactions were carried out with 2 (0.23 mmol) and 3a (0.30 mmol)in solvent (1 mL) as indicated. [b] Isolated yield. [c] ee and >98:2 d.r.were determined by HPLC analysis. The minor diastereomer was not de-tected in the crude 1H NMR spectrum.

Table 2. Substrate scope of the AgOAc/(R)-1 e-catalyzed asymmetric 1,3-dipolar cycloaddition of sulfonylacrylate 2 with various imino esters 3.[a]

Entry R 4 Yield[b] [%] ee[c] [%]

1 p-ClPh (3a) 4 a 82 992 p-BrPh (3b) 4 b 84 993 p-FPh (3 c) 4 c 82 994 p-CNPh (3d) 4 d 85 995 o-ClPh (3e) 4 e 83 966 Ph (3 f) 4 f 85 997 p-MePh (3 g) 4 g 85 998 o-MePh (3 h) 4 h 86 979 m-MePh (3 i) 4 i 89 96

10 p-MeOPh (3j) 4 j 73 9911 2-naphthyl (3k) 4 k 83 9912 2-furyl (3 l) 4 l 87 9613 2-thienyl (3m) 4 m 84 9914 isopropyl (3n) – – –15 cinnamyl (3 o) – – –

[a] All reactions were carried out with 2 (0.23 mmol) and 3 (0.30 mmol)in EtOAc (1 mL). [b] Isolated yield. [c] ee and>98:2 d.r. were determinedby chiral HPLC analysis. The minor diastereomer was not detected in thecrude 1H NMR spectrum.

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COMMUNICATION

To further confirm the unusual regiochemial control ofthis cycloaddition and determine the absolute configurationof the adduct, a single-crystal X-ray diffraction study of 4 jwas performed and its absolute configuration was unequivo-cally assigned as (2R,3R,4S,5R)[13] (Figure 1).

The cycloaddition products containing a sulfonyl groupcan be readily converted into synthetically useful and other-wise inaccessible compounds, as exemplified in Scheme 3.Desulfonylation of 4 f, followed by tautomerization, led tothe cyclic imine 5 without loss of diastereo- and enantiomer-ic excess. Treatment of the cycloadduct 4 n, derived from ana-substituted imino ester, under the same reaction condi-tions afforded 2,5-dihydro-1H-pyrrole derivative 6, probably,because the similar elimination and tautomerization routewas efficiently suppressed by the quaternary carbon stereo-genic center adjacent to the N atom.

To rationalize the mechanism and the stereoselectivity ofthis cycloaddition reaction, density functional theory (DFT)studies have been performed.[14] The full reaction pathwaywas explored with the substrates 2, 3 f (R1 =Ph), and a sim-plified ligand of (R)-1 e, in which methyl groups were usedinstead of phenyl groups on the phosphorus. The configura-tions of the calculated models are in correspondance to theadduct 4 in the experiment. As shown in Figure 2, this cyclo-addition reaction proceeds through a stepwise mechanism.In these five structures, the distance between the N atom ofthe NH2 group and the Ag center ranges from 3.288 to3.846 �, indicating that there are no strong interactions be-

Figure 1. X-ray crystallographic structure of (2R,3R,4S,5R)-4j.

Scheme 3. Synthetic transformation of the cycloadducts 4 f and 4 n.

Figure 2. The calculated reaction pathway with simplified models. The relative free energies DGsol are in kcal mol�1, the distances are in �. Calculated atM06/(6-31G* and 6-31 +G**) level in CH2Cl2 solvent.

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Y.-X. Li, C.-J. Wang et al.

tween them. Each structure has double hydrogen bonds be-tween the two electron-withdrawing groups in the (Z)-sulfo-nyl acrylate and the NH2 group of the chiral ligand. Ap ACHTUNGTRENNUNGpar-ACHTUNGTRENNUNGent ACHTUNGTRENNUNGly, these double hydrogen bonds should account for thehigh endo selectivity, since they direct the two substituentsof the acrylate towards the Ag center at the same side withthe N atom in the azomethine ylide. The nucleophilic attack(TS1) of Ca on the azomethine ylide to the Cc of the acrylateleads to a zwitterionic intermediate Int, in which the Ca�Cc

bond is nearly fully formed (1.600 �), the accumulatedNBO (natural bond orbitals) charges delocalized on Cd, andthe ester group is �0.712. In TS1, and especially in Int, thedouble hydrogen bonds become stronger, indicating thatthey can stabilize the transition state and the intermediate,that is, activate the acrylate. The ring-closing step TS2 leadsto the final product P.

As shown in Figure 2, the stereoselectivity should be con-trolled by the first step (TS1) of the reaction. Four transitionstates of the first step, corresponding to the four possiblestereoisomers, were constructed and fully optimized(Figure 3). The complete models of substrates 2, 3 f, and theligand (R)-1 e were used in the calculation. The results are

in good agreement with the experimental observations, andthe most favorable transition state TS1-a will lead to prod-uct 4 f. Other transition states are at least 4.5 kcal mol�1

higher in energy, indicating excellent enantioselectivity (cal-culated ee= 99.8 %). The transition states in Figure 3 havesome common features: the carbon atom Cc, linked with thesulfonyl group, is more reactive and forms the first C�Cbond with Ca or Cb of the azomethine ylide. The transitionstates forming the Cc�Ca bond (TS1-a and TS1-a’) are morestable than those forming the Cc�Cb bond (TS1-b and TS1-b’).

The unusual ester-directing regioselectivity can be ration-alized as follows: the resonance structures in Scheme 4a

show that Ca has more negative charge and consequently ahigher reactivity towards nucleophilic attack. In the reactantR, shown in Figure 1, the calculated NBO charges on Ca andCb are �0.236 and �0.013, respectively. On the other hand,for the (Z)-sulfonyl acrylate in a stepwise mechanism, Cc

should more readily undergo nucleophilic attack, owing tothe accumulated charge being delocalized on Cd and theester group (A in Scheme 4b). However, an isolated nega-tive charge will accumulate on Cc, when Cd undergoes nucle-ophilic attack (B in Scheme 4b). The small models A and Bwith R=H in Scheme 4b were calculated (see Figure S2 inthe Supporting Information);[14] A is more stable than B by9.5 kcal mol�1. The negative charge on Cc in B is �0.940,which is much larger than that on Cd (�0.623) in A. There-fore, in a stepwise reaction, when the large negative chargeon Cc in B cannot be stabilized by the catalyst or othergroups in the system, and there are no significant steric ef-fects exerting on the sulfonyl and ester groups, the best reac-tion mode is that Ca of the azomethine ylide attacks Cc ofthe acrylate.

The origin of the enantioselectivity can be easily under-stood from Figures 3 and 4. In TS1-a, the phenyl group ofthe azomethine ylide takes the empty right side, whereas inthe less stable TS-a’ this phenyl group is at the crowded leftside and encounters a steric clash with the TF-Bipham back-bone of the ligand. Therefore, ligand 1 e with a larger Bratom as the R1 group can produce higher ee values.

Figure 3. The four optimized transition states corresponding to the fourpossible stereoisomers of TS1. The relative free energies DGsol are in kcalmol�1, the distances are in �. Calculated at M06/(6-31G* and 6-31+

G**) level in CH2Cl2 solvent.

Scheme 4. Small models A and B to rationalize the regioselectivity.

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COMMUNICATIONAsymmetric 1,3-Dipolar Cycloaddition

In conclusion, we have reported the first catalytic, asym-metric 1,3-dipolar cycloaddition of imino esters and unsym-metrically 1,2-diactivated (Z)-sulfonyl acrylate with unusualregioselectivity that is controlled by the ester group ratherthan the sulfonyl group. The highly efficient AgI/TF-Bi-phamPhos catalytic system exhibited excellent diastereo-and enantioselectivity, and a broad substrate scope. Subse-quent transformation of the cycloadducts led to expedientpreparation of synthetically useful cyclic imine and dihydro-pyrrole derivatives. Theoretical calculations revealed a step-wise mechanism for this highly selective 1,3-dipolar cycload-dition, and the hydrogen-bonding interactions between thetwo different electron-withdrawing groups in (Z)-sulfonylacrylate and the NH2 group of the chiral ligand TF-Bipham-Phos played a significant role in the high endo selectivity.The unusual ester-directed regioselectivity and excellentenantioselectivity were also rationalized.

Experimental Section

General procedure for the asymmetric 1,3-dipolar cycloaddition of azo-methine ylides with (Z)-methyl 3-(phenylsulfonyl)-acrylate catalyzed byAgOAc/TF-BiphamPhos complex 1e: Under an argon atmosphere, (R)-TF-BiphamPhos (1e, 5.73 mg, 0.007 mmol) and AgOAc (1.2 mg,0.007 mmol) were dissolved in ethyl acetate (1 mL) and stirred at 0 8C forapproximately 1 h. Then, the imine substrate (0.30 mmol) was added, fol-lowed by Et3N (0.04 mmol) and (Z)-methyl 3-(phenylsulfonyl)-acrylate(2, 52 mg, 0.23 mmol). When the starting material was consumed (moni-tored by TLC), the mixture was filtered through Celite and the filtratewas concentrated to dryness. The crude product was analyzed by1H NMR spectroscopy to determine the endo to exo ratio. Then, the resi-due was purified by column chromatography to give the correspondingcycloaddition product as a white solid, which was directly analyzed bychiral HPLC to determine the enantiomeric excess.

Acknowledgements

This work is supported by the National Natural Science Foundation ofChina (20972117, 20872168), the Program for New Century ExcellentTalents in university (NCET-10-0649), the Program for ChangjiangScholars and Innovative Research Team in University of the Ministryof Education (IRT1030), 973 program (2011CB808600), SRFDP

(20090141110042), and the Fundamental Research Funds for the CentralUniversities.

Keywords: asymmetric catalysis · cycloaddition · densityfunctional calculations · diactivated alkenes · regioselectivity

[1] a) L. M. Harwood, R. J. Vickers in Synthetic Applications of 1,3-Di-polar Cycloaddition Chemistry Toward Heterocycles and NaturalProducts (Eds.: A. Padwa, W. Pearson), John Wiley & Sons, NewYork, 2002.

[2] For recent reviews on 1,3-dipolar cycloaddition reactions of azome-thine ylides, see: a) J. Adrio, J. C. Carretero, Chem. Commun. 2011,47, 6874; b) B. Engels, M. Christl, Angew. Chem. 2009, 121, 8110;Angew. Chem. Int. Ed. 2009, 48, 7968; c) L. M. Stanley, M. P. Sibi,Chem. Rev. 2008, 108, 2887; d) M. �lvarez-Corral, M. MuÇoz-Dorado, I. Rodr�guez-Garcıa, Chem. Rev. 2008, 108, 3174; e) G.Pandey, P. Banerjee, S. R. Gadre, Chem. Rev. 2006, 106, 4484; G.Pandey, P. Banerjee, S. R. Gadre, Chem. Rev. 2006, 106, 4484; f) I.Coldham, R. Hufton, Chem. Rev. 2005, 105, 2765.

[3] For recent examples on Ag catalysts, see: a) Y. Yamashita, X.-X.Guo, R. Takashita, S. Kobayashi, J. Am. Chem. Soc. 2010, 132, 3262;b) Y. Yamashita, I. Takaki, S. Kobayashi, Angew. Chem. 2011, 123,4995; Angew. Chem. Int. Ed. 2011, 50, 4893; c) R. Robles-Mach�n, I.Alonso, J. Adrio, J. C. Carretero, Chem. Eur. J. 2010, 16, 5286; d) I.Oura, ; K. Shimizu, K. Ogata, S.-i. Fukuzawa, Org. Lett. 2010, 12,1752; K. Shimizu, K. Ogata, S.-i. Fukuzawa, Org. Lett. 2010, 12,1752; e) H. Y. Kim, H.-J. Shih, W. E. Knabe, K. Oh, Angew. Chem.2009, 121, 7556; Angew. Chem. Int. Ed. 2009, 48, 7420; f) C. N�jera,M. de Garcia Retamosa, J. M. Sansano, Angew. Chem. 2008, 120,6144; Angew. Chem. Int. Ed. 2008, 47, 6055; g) W. Zeng, G.-Y.Chen, Y.-G. Zhou, Y.-X. Li, J. Am. Chem. Soc. 2007, 129, 750;h) T. F. Knçpfel, P. Aschwanden, T. Ichikawa, T. Watanabe, E. M.Carreira, Angew. Chem. 2004, 116, 6097; Angew. Chem. Int. Ed.2004, 43, 5971; i) C. Chen, X. Li, S. L. Schreiber, J. Am. Chem. Soc.2003, 125, 10174; j) J. M. Longmire, B. Wang, X. Zhang, J. Am.Chem. Soc. 2002, 124, 13400.

[4] For recent examples on Zn catalysts, see: a) A. S. Gothelf, K. V.Gothelf, R. G. Hazell, K. A. Jørgensen, Angew. Chem. 2002, 114,4410; Angew. Chem. Int. Ed. 2002, 41, 4236; b) O. Dogan, H. Koyun-cu, P. Garner, A. Bulut, W. J. Youngs, M. Panzner, Org. Lett. 2006,8, 4687.

[5] For recent examples on Cu catalysts, see: a) T. Arai, A. Mishiro, N.Yokoyama, K. Suzuli, H. Sato, J. Am. Chem. Soc. 2010, 132, 5338;b) A. L�pez-P�rez, J. Adrio, J. C. Carretero, J. Am. Chem. Soc.2008, 130, 10 084; c) S.-i. Fukuzawa, H. Oki, Org. Lett. 2008, 10,1747; d) S. Cabrera, R. G. Array�s, B. Mart�n-Matute, F. P. Coss�o,J. C. Carretero, Tetrahedron 2007, 63, 6587; e) M. Shi, J.-W. Shi, Tet-rahedron: Asymmetry 2007, 18, 645; f) X.-X. Yan, Q. Peng, Y.Zhang, K. Zhang, W. Hong, X.-L. Hou, Y.-D. Wu, Angew. Chem.2006, 118, 2013; Angew. Chem. Int. Ed. 2006, 45, 1979; g) T. Llamas,R. G. Array�s, J. C. Carretero, Org. Lett. 2006, 8, 1795; h) S. Cab-rera, R. G. Array�s, J. C. Carretero, J. Am. Chem. Soc. 2005, 127,16394; i) W. Gao, X. Zhang, M. Raghunath, Org. Lett. 2005, 7, 4241;j) C. Zhang, S.-B. Yu, X.-P. Hu, D.-Y. Wang, Z. Zheng, Org. Lett.2010, 12, 5542; k) A. P. Antonchick, C. Gerding-Reimers, M. Catari-nella, M. Schrmann, H. Preut, S. Ziegler, D. Rauh, H. Waldmann,Nat. Chem. 2010, 2, 735.

[6] For recent examples on Ni catalysts, see: a) T. Arai, N. Yokoyama,A. Mishiro, H. Sato, Angew. Chem. 2010, 122, 8067; Angew. Chem.Int. Ed. 2010, 49, 7895; b) J.-W. Shi, M.-X. Zhao, Z.-Y. Lei, M. Shi,J. Org. Chem. 2008, 73, 305.

[7] For recent examples on Ca catalysts, see: a) S. Saito, T. Tsubogo, S.Kobayashi, J. Am. Chem. Soc. 2007, 129, 5364; b) T. Tsubogo, S.Saito, K. Seki, Y. Yamashita, S. Kobayashi, J. Am. Chem. Soc. 2008,130, 13321.

Figure 4. The top view of TS1-a and TS1-a’.

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Y.-X. Li, C.-J. Wang et al.

[8] For examples on organocatalysts, see: a) J. L. Vicario, S. Reboredo,D. Bad�a, L. Carrillo, Angew. Chem. 2007, 119, 5260; Angew. Chem.Int. Ed. 2007, 46, 5168; b) I. Ibrahem, R. Rios, J. Vesely, A. Cordo-va, Tetrahedron Lett. 2007, 48, 6252; c) X.-H. Chen, W.-Q. Zhang,L.-Z. Gong, J. Am. Chem. Soc. 2008, 130, 5652; d) C. Guo, M.-X.Xue, M.-K. Zhu, L.-Z. Gong, Angew. Chem. 2008, 120, 3462;Angew. Chem. Int. Ed. 2008, 47, 3414; e) Y-K. Liu, H. Liu, W. Du,L. Yue, Y.-C. Chen, Chem. Eur. J. 2008, 14, 9873.

[9] a) A. L�pez-P�rez, J. Adrio, J. C. Carretero, Angew. Chem. 2009,121, 346; Angew. Chem. Int. Ed. 2009, 48, 340; b) R. Robles-Mach�n,M. Gonz�lez-Esguevillas, J. Adrio, J. C. Carretero, J. Org. Chem.2010, 75, 233.

[10] a) C.-J. Wang, G. Liang, Z.-Y. Xue, F. Gao, J. Am. Chem. Soc. 2008,130, 17250; b) C.-J. Wang, Z.-Y. Xue, G. Liang, Z. Lu, Chem.Commun. 2009, 2905; c) G. Liang, M.-C. Tong, C.-J. Wang, Adv.Synth. Catal. 2009, 351, 3101; d) Z.-Y. Xue, T.-L. Liu, Z. Lu, H.Huang, H.-Y. Tao, C.-J. Wang, Chem. Commun. 2010, 46, 1727; e) G.Liang, M.-C. Tong, H.-Y. Tao, C.-J. Wang, Adv. Synth. Catal. 2010,352, 1851; f) T.-L. Liu, Z.-Y. Xue, H.-Y. Tao, C.-J. Wang, Org.Biomol. Chem. 2011, 9, 1980; g) T.-L. Liu, Z.-L. He, H.-Y. Tao, Y.-P.

Cai, C.-J. Wang, Chem. Commun. 2011, 47, 2616; h) H.-L. Teng, H.Huang, H.-Y. Tao, C.-J. Wang, Chem. Commun. 2011, 47, 5494.

[11] The AgI or CuI/rac-(�)-TF-BiphamPhos (1a)-catalyzed reaction of(E)-sulfonyl acrylate 2 with glycine imino ester 3a delivered a mix-ture of isomers that could not be separated by chromatography.

[12] Quaternary Stereocenters: Challenges and Solution for Organic Syn-thesis (Eds.: J. Christoffers, A. Baro), Wiley-VCH, Weinheim, 2005.

[13] Crystal data for (2R,3R,4S,5R)-4j : C21H23NO7S; Mr =433.46; T=

293 K; monoclinic; space group P21; a =12.9796(8), b=5.7493(4),c= 14.8287(10) �; V =1032.33(12) �3; Z =2; 3329 unique reflec-tions; final R1 =0.0282 and wR2 =0.0728 for 3428 observed [I>2s(I)] reflections. Flack c =0.03(6) CCDC 822412 contains the sup-plementary crystallographic data for this paper. These data can beobtained free of charge from The Cambridge Crystallographic DataCentre via www.ccdc.cam.ac.uk/data_request/cif.

[14] See the Supporting Information for details.

Received: August 5, 2011Published online: October 5, 2011

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COMMUNICATIONAsymmetric 1,3-Dipolar Cycloaddition