A Versatile Ru Catalyst for the Asymmetric Transfer Hydrogenation of Both Aromatic and Aliphatic Sulfinylimines

Abstract

A highly efficient Ru catalyst based on an achiral, very simple, and inexpensive amino alcohol ligand (2-amino-2-methylpropan-1-ol) has been developed for the asymmetric transfer hydrogenation (ATH) of chiral N-(tert-butylsulfinyl)imines. This complex is able to catalyze the ATH of both aromatic and the most challenging aliphatic sulfinylimines by using isopropyl alcohol as the hydrogen source. The diastereoselective reduction of aromatic, heteroaromatic, and aliphatic sulfinylketimines, including sterically congested cases, over short reaction times (1-4 h), followed by desulfinylation of the nitrogen atom, affords the corresponding highly enantiomerically enriched (ee up to >99 %) α-branched primary amines in excellent yields. The same ligand was equally effective for the synthesis of both (R)- and (S)-amines by using the appropriate absolute configuration in the iminic substrate. DFT mechanistic studies show that the hydrogen-transfer process is stepwise. Moreover, the origin of the diastereoselectivity has been rationalized.

Chiral β-Amino Alcohols as Ligands for the Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation of N-Phosphinyl Ketimines

“…Since those ligands have shown to give excellent results in the ruthenium-catalyzed asymmetric transfer hydrogenation of ketones [12][13][14][15][16][17][18][19] and N-sulfinylimines [38][39][40][41] in isopropyl alcohol, we decided to investigate if they could also be applied to the reduction of N-phosphinyl ketimines by the same methodology. One of the most noteworthy chiral β-amino alcohols in the ATH of both ketones and N-sulfinyl imines is cis-1-amino-2-indanol [50].…”

“…A slight improvement of both yield and enantioselectivity were observed when the initial temperature was −20 °C instead of 0 °C (Table 1, entry 12). Since in our previous studies concerning the ATH of N-(tert-butylsulfinyl)imines [38][39][40][41] we found that potassium tert-butoxide was a more convenient base than potassium hydroxide, we decided to evaluate the former in the ATH of phosphinylimine 1a and we obtained a further improvement, giving 87% yield and 82% ee (Table 1, entry 13). A decrease of the initial temperature to −40 °C slightly reduced both the yield and the enantiomeric excess (Table 1, entry 14).…”

“…Although the transfer hydrogenation protocol has been already applied to the reduction of different iminic substrates bearing alkyl [18], benzyl [17,18], aryl [17,18], sulfonyl [13,18,37] or sulfinyl [38][39][40][41] groups attached to the nitrogen atom, there are only a few examples on the use of N-phosphinyl imines as substrates [18,42]. In the last years, we have been interested in the use of β-amino alcohols as ligands for ruthenium complexes used as catalysts for the ATH of imines, especially N-(tert-butylsulfinyl)imines [38][39][40][41].…”

“…In the last years, we have been interested in the use of β-amino alcohols as ligands for ruthenium complexes used as catalysts for the ATH of imines, especially N-(tert-butylsulfinyl)imines [38][39][40][41]. Since, to the best of our knowledge, the use of β-amino alcohols as chiral ligands has not been reported so far for the ATH of N-(diphenylphosphinyl)imines, we became interested in trying to apply our methodology to those substrates.…”

Synthesis of Highly Enantiomerically Enriched Amines by Asymmetric Transfer Hydrogenation of N-(tert-Butylsulfinyl)Imines

“…Thus, highly enantiomerically enriched -branched primary amines are obtained in excellent yields by the diastereoselective reduction of a variety of sulfinylimines followed by desulfinylation of the nitrogen atom. 10 The N-(tert-butylsulfinyl)imines are prepared by reaction of stoichiometric amounts of the corresponding ketones and 2-methylpropane-2-sulfinamide in the presence of two equivalents of Ti(OEt) 4 under solventfree conditions. 11 The obtained imines 3 are reduced by asymmetric transfer hydrogenation using isopropyl alcohol as hydrogen source and, as a catalyst, a ruthenium complex bearing a commercially available simple achiralaminoalcohol: 2-amino-2-methylpropan-1-ol.…”