Efficient\nRu-Catalyzed Transfer Hydrogenation of Bulky\nKetones Imparted by a Monosubstituted Amino-Carbene Ligand

While catalytic transfer hydrogenation of ketones is\nwell established\nfor model substrates, major limitations are faced when applying this\nmethodology to sterically encumbered carbonyl substrates. To address\nthis challenge, we have here combined the catalytic competence of\nruthenium together with a unique monosubstituted amino-carbene (MAC)\nas a ligand to produce a ruthenium complex, <b>Ru-MAC</b>, which\nfeatures a markedly reduced buried volume. We demonstrate that <b>Ru-MAC</b> is a transfer hydrogenation catalyst with outstanding\nactivity when compared to other related ruthenium complexes such as <b>Ru-IMes</b>, the analogue containing the Arduengo-type <i>N,N′</i>-mesityl substituted imidazolylidene ligand.\nThe catalytic acceleration factor of <b>Ru-MAC</b> is particularly\npronounced with sterically bulky ketones. Multivariate regression\nanalysis allowed us to deduce a model that quantitatively correlates\nthe steric parameters of the substrates with the catalytic acceleration\nfactor, revealing paramount relevance of the minimum width of the\nlarger ketone substituent, <i>viz</i>. Sterimol parameter <i>B<sub>1L</sub></i>. The exquisite activity of <b>Ru-MAC</b> is further demonstrated by the transfer hydrogenation, for the first\ntime, of two extremely hindered substrates, namely 2,4,6-triisopropylacetophenone\nand pentamethylacetophenone, to quantitatively yield the corresponding\nalcohols.