Dition of azlactonesFigure 1. Cinchonatype catalysts tested for the organocatalytic [3 2]cycloaddition of munchnones onto [60]fullerene.onto methyleneindolinone (Figure 1).13 On the other hand, and not surprisingly, they didn’t display any enantioselectivity. Certainly, these catalysts can only activate azlactones by implies of the nitrogen base, although the LUMO activation by hydrogen bond with thiourea will not take location in fullerenes. The usage of phase transfer catalysts 7ah (PTC, Figure two) in toluene/basic water achieved the formation of no racemicFigure two. PTCs tested for the organocatalytic [3 2] cycloaddition of munchnones onto [60]fullerene.mixtures of 2a. Nonetheless, the enantioselectivities obtained were poor even at low temperature, as soon as once more in contrast to that previously reported within the literature.19 Ultimately, we turn our consideration into chiral Nheterocyclic carbenes (NHCs). These compounds have already been broadly employed as ligands in metal catalysis,20 though far more recently have seasoned an awesome interest in organocatalysis.21 Within this regard, NHCs have been made use of as Br sted base catalysts capable to create alkoxides and enolates in transesterification reactions22 or Claisen condensations,23 respectively. With this in mind, we tested several commercially readily available chiraldx.doi.org/10.1021/ja500071k | J. Am. Chem. Soc. 2014, 136, 2897Journal from the American Chemical Society triazolium salts (811) as NHC precursors by reaction with ten equiv of NaH in anhydrous toluene (Figure 3 and Table 1). Beneath these reaction circumstances, we had been able to isolate the desirable adduct 2a in variable conversions (Table 1, entries 14) but in outstanding enantiomeric excess (ee) when 1 equiv on the triazolium salt 8a was utilized (entry 1). Several bases with variableArticleFigure 3. NHCs tested for the organocatalytic [3 2] cycloaddition of munchnones onto [60]fullerene.Table 1. Screening of NHCs within the Cycloaddition of Azlactone 1a with [60]Fullereneaentry NHC 1 2 three four five 6 7 8 9 ten 11 12 13 14 15 16 17 18 19 20 21 22 23dabase (equiv) NaH (ten) NaH (ten) NaH (ten) NaH (10) KI (10) Na2CO3 (ten) NaHCO3 (ten) KHDMS (10) DBU (ten) KOH (ten) NaH (1) NaH (five) NaH (one hundred) NaH (1000) NaH (ten) NaH (10) NaH (10) NaH (ten) NaH (ten) NaH (10) NaH (10) NaH (ten) NaH (ten)solvent toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene CS2 CH3CN oDCB PhCl toluene toluene toluene toluene tolueneT ( ) rt rt rt rt rt rt rt rt rt rt rt rt rt rt rt rt rt rt 0 30 50 rt rtconv.tert-Butyl 5-aminopentanoate supplier b ( ) 99 10 98 11 four 33 37 96 98 45 78 37 89 85 eight ten 99 99eeb ( ) productc 88 (S)2a 16 (S)2a 16 (R)2a 22 (R)2a 0 34 (S)2a 4 (S)2a 74 (S)2a 72 (S)2a 72 (S)2a 76 (S)2a 80 (S)2a 68 (S)2a 36 (S)2a 84 (S)2a 34 (S)2a 54 (S)2a 84 (R)2a 64 (S)2a8a 9 ten 11 8a 8a 8a 8a 8a 8a 8a 8a 8a 8a 8a 8a 8a 8a 8a 8a 8a 8b 8aGeneral reaction circumstances: A mixture from the triazolium salt (NHC, 1 equiv), [60]fullerene (1 equiv), plus the base (ten equiv) in 1 mL of solvent is stirred for ten min at rt, then 0.N-(2-Hydroxyethyl)methacrylamide site 016 mmol of azlactone 1a (two equiv) is added.PMID:23795974 Soon after 30 min of reaction, excess of DCC is added. b Conversion and ee happen to be determined by HPLC evaluation. c Absolute configuration has been assigned on the base of CD measurements. d10 mol of 8a is employed.basicity have been evaluated (entries 510) demonstrating that stronger bases such as KOH (entry 10) worked much better with regards to conversion and enantioselectivity than weaker ones like Na2CO3 (entry 6). Having said that, when DBU, broadly utilized with this kind of NHCs.