Third‐Generation Amino Acid Furanoside‐Based Ligands from d‐Mannose for the Asymmetric Transfer Hydrogenation of Ketones: Catalysts with an Exceptionally Wide Substrate Scope

Abstract

A modular ligand library of α‐amino acid hydroxyamides and thioamides was prepared from 10 different N‐tert‐butyloxycarbonyl‐protected α‐amino acids and three different amino alcohols derived from 2,3‐O‐isopropylidene‐α‐d‐mannofuranoside. The ligand library was evaluated in the half‐sandwich ruthenium‐ and rhodium‐catalyzed asymmetric transfer hydrogenation of a wide array of ketone substrates, including simple as well as sterically demanding aryl alkyl ketones, aryl fluoroalkyl ketones, heteroaromatic alkyl ketones, aliphatic, conjugated and propargylic ketones. Under the optimized reaction conditions, secondary alcohols were obtained in high yields and in enantioselectivities up to >99%. The choice of ligand/catalyst allowed for the generation of both enantiomers of the secondary alcohols, where the ruthenium‐hydroxyamide and the rhodium‐thioamide catalysts act complementarily towards each other. The catalytic systems were also evaluated in the tandem isomerization/asymmetric transfer hydrogenation of racemic allylic alcohols to yield enantiomerically enriched saturated secondary alcohols in up to 98% ee. Furthermore, the catalytic tandem α‐alkylation/asymmetric transfer hydrogenation of acetophenones and 3‐acetylpyridine with primary alcohols as alkylating and reducing agents was studied. Secondary alcohols containing an elongated alkyl chain were obtained in up to 92% ee.magnified image

Ruthenium(II) complexes bearing (NNN) ligand: catalytic evaluation of different solvent-mediated coordination modes

“…In spite of the loss of p-cymene moiety, the mechanism of ATH probably involved, also in this case, a classical catalytic cycle. [37][38][39][40] Taking into consideration the differences in both structural coordination mode, our complexes resulted less active and straightly less stereoselective in comparison with other similar catalytic systems reported in literature. 16,35,[41][42] In those systems better results might depend on the presence of an additive in formation of bimetallic 6-membered transition state or in alternative on the presence of an additional phosphine ligand known for reducing the acidity of metal center that favors the hydride transfer.…”

Synthesis of C2-Symmetric Bisphosphines and Their Application in Enantioselective Transition Metal Catalysis

“…Performing the reaction with bisphosphine ligand 11, we observed in all cases poor enantioselectivity and poor to excellent conversion (Table 1, entries [22][23][24][25][26]. We determined poor results under the catalysis of bisphosphine ligand 12 except chemical yields of the reaction treating with AcOK ( Table 1, entries [27][28][29][30][31].…”

“…[21][22][23][24][25][26][27] The asymmetric transfer hydrogenation (ATH) or reduction of ketones allows the production of a large number of useful chiral alcohols that are ubiquitous in nature and are in great demand for flavors and fragrances, for pharmaceuticals, and for agrochemicals. [28][29][30][31][32][33][34][35] Apart from some procedures, ATH includes some interesting advantages such as using environmentally friendly solvents, low catalyst loading, safe application and volatile byproducts. Consequently, it can be easily applied to industrial processes.…”

Biocatalytic asymmetric synthesis of (R)‐1‐tetralol using Lactobacillus paracasei BD101

“…10 To date, many chemical catalysts have been used for asymmetric reduction of 1-tetralone (1) and its derivatives, such as iridiumcatalyzed ligands, oxazaborolidine, amino acid-based ligands, and lutidine-based ligands. [11][12][13][14][15] In the literature, various chemical catalysts were tested for asymmetric reduction of substrate 1. However, to our knowledge, the use of biocatalyst for reduction of 1 has limited.…”