Highly Enantioselective One-Pot Synthesis of Chiral β-Heterosubstituted Alcohols via Ruthenium–Prolinamide-Catalyzed Asymmetric Transfer Hydrogenation

Abstract

The utility of a chiral Ru–prolinamide catalytic system has been demonstrated in one-pot synthesis of optically active β-triazolylethanol and β-hydroxy sulfone derivatives. The said methodology proceeds through asymmetric transfer hydrogenation of in situ formed ketones of the corresponding chiral products. Various chiral prolinamide ligands were screened, and ligand L6 with isopropyl groups substituted at the ortho position has shown excellent activity at 60 °C in aqueous medium producing up to 95% yield and 99.9% enantioselectivity.

Chemoenzymatic Oxosulfonylation‐Bioreduction Sequence for the Stereoselective Synthesis of β‐Hydroxy Sulfones

“…On the other hand, the elution order of the chemoenzymatically obtained 4 a enantiomers using a Chiralcel AD−H column was compared with the one reported in the literature, finding a clear trend and appearing first the ( R )‐enantiomer when using the same chiral stationary phase. [ 4d , 4f , 4g , 4h ] Similarly, the enantiomer elution orders for 4 b [ 4g , 4h ] and 4 h [24a] in the same column, and also for 4 c [4h] and 4 d [ 4g , 4h , 4i ] in the Chiralcel OJ−H were in agreement with our previous assignment based on their optical rotation values. As pointed out before, it seems that an opposite elution order has been wrongly proposed by Liu and co‐workers and Zhou and co‐workers when using a ruthenium catalyst.…”

Recent Progress on the Synthesis of Chiral Sulfones

“…In 2018, Bhanage's group explored the utility of chiral Ru(II)‐prolinamide catalytic system in the one‐pot synthesis of β‐hydroxy sulfone derivatives (Scheme 45). [59] Various chiral prolinamide ligands were screened, and ligand L 27 with isopropyl groups substituted had an excellent catalytic effect, the chiral prolinamide L 27 promoted the asymmetric hydrogenation between 95 and sodium sulfinates to furnish a variety of chiral β‐hydroxy sulfones 96 in excellent yields (80–93 %) and high enantioselectivities (93.6–99.9 % ee).…”

Efficient synthesis of an apremilast precursor and chiral β-hydroxy sulfones via ketoreductase-catalyzed asymmetric reduction

“…4 Therefore, some methods for the synthesis of these compounds were developed in the last two decades, such as asymmetric conjugate boration of α,β-unsaturated sulfones 5 and asymmetric reduction of β-keto sulfones, including borane reduction, [6][7][8] transition metal-catalyzed asymmetric hydrogenation [9][10][11][12][13] and asymmetric transfer hydrogenation. [14][15][16][17][18][19] However, the generality of these approaches is often plagued by high-pressure conditions, the use of intricate chiral-ligand catalysts or heavy metal pollution. Biocatalytic methods were also developed for the synthesis of β-hydroxy sulfones, such as dynamic kinetic resolution of racemic β-hydroxy sulfones by lipase 20 and asymmetric bioreduction of β-keto sulfones by whole cells.…”