Development of Chiral Spiro P‐N‐S Ligands for Iridium‐Catalyzed Asymmetric Hydrogenation of β‐Alkyl‐β‐Ketoesters

Abstract

The chiral tridentate spiro P-N-S ligands (SpiroSAP) were developed, and their iridium complexes were prepared. Introduction of a 1,3-dithiane moiety into the ligand resulted in a highly efficient chiral iridium catalyst for asymmetric hydrogenation of β-alkyl-β-ketoesters, producing chiral β-alkyl-β-hydroxyesters with excellent enantioselectivities (95-99.9% ee) and turnover numbers of up to 355,000.

Readily Accessible and Highly Efficient Ferrocene‐Based Amino‐Phosphine‐Alcohol (f‐Amphol) Ligands for Iridium‐Catalyzed Asymmetric Hydrogenation of Simple Ketones

“…[3] The excellent reactivities and enantioselectivitiesa re mainly due to the cooperative action of the RuÀHa nd NH 2 group through am etal-ligand bifunctionalm echanismi nvolving the "NH effect". Encouraged by these results, many bidentate and tridentate ligandsh ave been developed for asymmetrich ydrogenation of ketones in the last decades, such as PP, [4] NN, [5] NNN, [6] PNN, [7] PNS-type [8] ligands. For example, Zhou and coworkers have developed tridentate spiro-pyridine-aminophosphine ligands SpiroPAP by introducing an additional coordinating pyridyl group into SpiroAP ligand (Scheme 1), and chiral alcohols weref ormed with excellent resultsi nthe iridium-Spiro-PAPc atalytic system.…”

Tuning Rh(II)-Catalyzed Cyclopropanation with Tethered Thioether Ligands

“…A stereogenic center is created at the sulfur atom upon coordination to the Rh center. [51][52][53][54] As a result, a mixture of diastereomers are present, (SC, RS) and (SC, SS), due to the sulfur stereogenic center and the S configuration at the asymmetric carbon on the bridging oxazolidinate (Figure 3). Of the four paddlewheel units, two are (SC, RS) and two structures are (SC, SS), with minor structural variations between them.…”

Bifunctional Homogeneous Catalysts Based on Ruthenium, Rhodium and Iridium in Asymmetric Hydrogenation

“…AH of ketones, lactones and -ketoesters using an iridium catalyst based on a P(NH)N spiro ligand by Zhou, Xie and co-workers. [219][220][221][222][223][224][225][226][227][228][229][230][231][232][233][234] This method provides one of the most impressive recent applications of Ir-bifunctional catalysts in asymmetric hydrogenation, in terms of both catalytic efficiency, enantioselectivity, substrate scope and synthetic potential. It is worth to note that Zhang, Yin and co-workers reported in parallel the synthesis of rather similar oxaspirocyclic chiral ligands and applied them to iridium-catalyzed direct asymmetric hydrogenation of Bringmann's lactones (Scheme 73a).…”

“…219 Such catalysts proved to be highly effective and enantioselective for the AH of an impressive variety of ketones, enones, -ketolactams, keto acids (Scheme 72a), or -ketoesters (Scheme 72b) and others. [220][221][222][223][224] Moreover, this type of iridium(III) catalyst was involved in several DKR processes and enabled the asymmetric total synthesis of compounds of biological interest like crinine-type alkaloids (Scheme 72c), gracilamine alkaloïds, (-)goniomitine, mulinane diterpenoids, (-)-hamigeran B, (-)-mesembrine and others. [225][226][227][228][229][230][231][232] A recent application to the AH/Dynamic kinetic resolution of racemic α-arylamino-γ-lactones and α-arylamino-δlactones led to the corresponding chiral 2-amino diols with high yields and enantioselectivities (Scheme 72d).…”