Of carbodiimides.17 Based on the earlier organocatalytic reports of [3 + 2] cycloaddition of iminoesters onto different activated double bonds,18 we decided to begin our screening focusing on the noncovalent catalysis, in unique, in cinchona alkaloid derivatives16 for their simple availability and their excellent final results in a significant variety of stereoselective nucleophilic additions to activated double bonds. Despite the potential of organic bases to promote such cycloaddition was confirmed, catalysts 3a-d and 4a,b, featuring one particular or two quinuclidine skeletons, respectively, were unable to afford any considerable enantiomeric excesses of pyrrolino[60]fullerene 2a (Figure 1). The thioureas 5a-c and squaramide six are also bifunctional catalysts featuring a chiral base plus a thiourea moiety incredibly comparable to the catalysts applied for the cycloaddition of azlactonesFigure 1.NSI-189 custom synthesis Cinchona-type catalysts tested for the organocatalytic [3 + 2]cycloaddition of munchnones onto [60]fullerene.onto methyleneindolinone (Figure 1).13 Even so, and not surprisingly, they did not display any enantioselectivity. Indeed, these catalysts can only activate azlactones by suggests of the nitrogen base, while the LUMO activation by hydrogen bond with thiourea doesn’t take spot in fullerenes. The usage of phase transfer catalysts 7a-h (PTC, Figure two) in toluene/basic water achieved the formation of no racemicFigure 2. PTCs tested for the organocatalytic [3 + 2] cycloaddition of munchnones onto [60]fullerene.mixtures of 2a. However, the enantioselectivities obtained have been poor even at low temperature, after once again in contrast to that previously reported within the literature.Verbenalin Cancer 19 Finally, we turn our interest into chiral N-heterocyclic carbenes (NHCs). These compounds have been broadly employed as ligands in metal catalysis,20 though far more not too long ago have knowledgeable a great interest in organocatalysis.21 In this regard, NHCs have already been applied as Br sted base catalysts capable to produce alkoxides and enolates in transesterification reactions22 or Claisen condensations,23 respectively. With this in mind, we tested numerous commercially offered chiraldx.doi.org/10.1021/ja500071k | J. Am. Chem. Soc. 2014, 136, 2897-Journal from the American Chemical Society triazolium salts (8-11) as NHC precursors by reaction with 10 equiv of NaH in anhydrous toluene (Figure three and Table 1). Under these reaction situations, we have been able to isolate the desirable adduct 2a in variable conversions (Table 1, entries 1-4) but in great enantiomeric excess (ee) when 1 equiv on the triazolium salt 8a was employed (entry 1).PMID:36628218 Quite a few 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 4 5 6 7 eight 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23dabase (equiv) NaH (ten) NaH (ten) NaH (ten) NaH (10) KI (ten) Na2CO3 (ten) NaHCO3 (10) KHDMS (ten) DBU (ten) KOH (ten) NaH (1) NaH (5) NaH (one hundred) NaH (1000) NaH (ten) NaH (10) NaH (10) NaH (ten) NaH (10) NaH (ten) NaH (10) NaH (10) NaH (ten)solvent toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene CS2 CH3CN o-DCB 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.b ( ) 99 10 98 11 four 33 37 – – 96 98 45 78 37 – – 89 85 8 10 99 99eeb ( ) productc 88 (S)-2a 16 (S)-2a 16 (R)-2a 22 (R)-2a 0 34 (S)-2a 4 (S.
