Reactivity or selectivity enhancement in organocatalytic Michael additions under ball milling conditions Rafał Kowalczyk Wrocław University of Science and Technology, Poland Malonates afford the access to d1 synthon also in a chiral fashion. However, acting as stabilized nucleophiles, their addition to the less reactive electrophiles met a serious limitation. 1 The simple replacement of oxoesters with bisthiomalonates resulted in an increase in reactivity. The activity of the bisthiomalonates forming a nucleophile could be tuned by the electronic nature of the thiol residue. Drawing from the soft enolization approach, Cinchona- based squaramides catalyzed the stereoselective additions to relatively weak acceptors such as chalcones, dienones, and en-ynones, affording the desired Michael adducts. Moreover, the reaction performed under solventless conditions in a ball mill 2 furnished the desired adducts up to six times faster along with the selectivities unreachable for standard conditions. The KS-DFT studies allowed us to rationalize the differences in the reactivity of oxo- versus thioesters along with the lack of chemoselectivity observed in solution, finally revealing the nature of plausible transition states. The green profile of transformations was also proved following mechanochemical iminium catalysis supported by chiral primary amines. Even more spectacular differences in reaction times were observed, but without significant erosion of stereoselectivity 3 for both bisthiomalonates and dibenzyl malonate. References 1. J. Wu, C. M. Young, A. A. Watts, A. M. Z. Slawin, G. R. Boyce, M. Bühl, and A. D. Smith, Org. Lett ., 2022, 24 , 4040. 2. (a) F. Cuccu, L. De Luca, F. Delogu, E. Colacino, N. Solin, R. Mocci, and A. Porcheddu, ChemSusChem , 2022, doi. org/10.1002/cssc.202200362; (b)J. L. Howard, Q. Cao, and D. L. Browne, Chem. Sci ., 2018, 9 , 3080. 3. M. T. J. Willias, L. C. Morrill, and D. L. Browne, ChemSusChem 2022, doi.org/10.1002/cssc.202102157.
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