Highly Active Cooperative Lewis Acid—Ammonium Salt Catalyst for the Enantioselective Hydroboration of Ketones

Abstract

Enantiopure secondary alcohols are fundamental high-value synthetic building blocks.One of the most attractive ways to get access to this compound class is the catalytic hydroboration. We describe an ew concept for this reaction type that allowed for exceptional catalytic turnover numbers (up to 15 400), which were increased by around 1.5-3 orders of magnitude compared to the most active catalysts previously reported. In our concept an aprotic ammonium halide moiety cooperates with an oxophilic Lewis acid within the same catalyst molecule.C ontrol experiments reveal that both catalytic centers are essential for the observed activity.Kinetic, spectroscopic and computational studies show that the hydride transfer is rate limiting and proceeds via ac oncerted mechanism, in whichh ydride at Boron is continuously displaced by iodide,r eminiscent to an S N 2r eaction. The catalyst, whichi s accessible in high yields in few steps,w as found to be stable during catalysis,r eadily recyclable and could be reused 10 times still efficiently working.

Recent Advances in Aluminum Compounds for Catalysis

“…The asymmetric hydroboration of ketones has extraordinary significance in the fields of biology and medicine. [33] In 2020, R. Peters et al [34] presented a catalyst (23) for the asymmetric hydroboration reaction of ketones (Scheme 3). A well-defined cooperative Lewis acid-ammonium salt (23) was synthesized.…”

“…Cooperative Lewis acid-ammonium salt(23) for asymmetric hydroboration of ketones. Reprinted from Ref [34]…”

Potassium tert-Butoxide Facilitated Amination of Carboxylic Acids with N,N-Dimethylformamide

“…1 H NMR (400 MHz, CDCl 3 ):  = 7.72-7.69 (m, 2 H), 7.53-7.50 (m, 2 H), 3.10 (s, 3 H), 2.93 (s, 3 H). 23 Yield: 34.4 mg (90%); yellow oil; PE/EtOAc (5:1). 1 H NMR (400 MHz, CDCl 3 ):  = 8.02-7.96 (m, 2 H), 7.53-7.46 (m, 2 H), 3.12 (s, 3 H), 2.95 (s, 3 H), 2.62 (s, 3 H).…”

Strategies of In Situ Generated Magnesium Catalysis in Asymmetric Reactions

“…In 2019, one enantioselective hydroboration of ketones was successfully achieved using simple binolate-Mg(II) catalysts by Rueping and co-workers as a breakthrough work (Scheme 3). 7,8 The reaction is highly interesting because it first identified binolate-Mg(II) complexes were effective catalyst for activation of HBpin, given the fact that in previous works only monoanionic ligands, such as β-diketiminato stabilized magnesium complexes, worked well in the hydroboration of unsaturated bonds via a Mg-H species as the key intermediate. 9 However, under this binolate-Mg(II) catalytic method, there was no Mg-alkyl bond remained after sequential neutralization processes to generate the Mg-H bond (Scheme 3, A).…”