Pyrrolidine‐Based P,O Ligands from Carbohydrates: Easily Accessible and Modular Ligands for the Ir‐Catalyzed Asymmetric Hydrogenation of Minimally Functionalized Olefins

Abstract

The potential of P,O‐iminosugar based ligands in the Ir‐catalyzed asymmetric hydrogenation of minimally functionalized olefins is presented. These new ligands were prepared from easily available carbohydrates (D‐mannose, D‐ribose and D‐arabinose). The stereochemical and polyfunctional diversity of carbohydrates allowed the modulation of the ligands, both from their electronic properties and the rigidity of their backbone. High enantioselectivities (ee’s up to 99 %) can be reached in the hydrogenation of selected tri‐ and disubstituted substrates.

Transition Metal Complexes with Amino Acids, Peptides and Carbohydrates in Catalytic Asymmetric Synthesis: A Short Review

“…Such modular architectures modularity were critical to obtain the most efficient catalyst (up to 99% ee enantioselectivity) for each type of olefin through the careful choice of ligand parameters. Previously, Prof. Diéguez et al synthesized pyrrolidine-based phosphine/phosphite-O/S ligands from inexpensive carbohydrates (Dmannose, D-ribose and D-arabinose) and Ir-complexes based on these ligands (34) [120], which showed high enantioselectivity (ee up to 99%) in the hydrogenation of model triand disubstituted substrates.…”

Iminosugar-Phosphines as Organocatalysts in the [3 + 2] Cycloaddition of Allenoates and N-Tosylimines

“…Starting from D-ribose (Scheme 3), pyrrolidine phosphine 7, which presents a shorter phosphine alkyl chain, was prepared following the procedure reported by us [23] that implies the ring opening of the cyclic carbamate 6 by reaction with KPPh 2 in THF. N-methyl derivative 9 [22] was prepared by reaction of 7 with methoxycarbonyl chloride affording 8 and subsequent reduction with LiAlH 4 in THF at reflux.…”

“…Standard acylation of 7 using benzoyl and pivaloyl chloride afforded the pyrrolidine derivatives 12 and 13, respectively, in excellent yields. Finally, the reaction of 7 with 3,5-bistrifluoromethylisothiocyanate gave the thiourea-phosphine derivative 14 [23] in moderate yield. Moreover, pyrrolidine 16 bearing a less rigid backbone skeleton compared with pyrrolidine 9, was prepared from 15 [23] by reaction with KPPh 2 in THF at reflux followed by treatment with methoxycarbonyl chloride and final reduction with LiAlH 4 in THF at reflux (Scheme 4).…”

“…Finally, starting from D-mannose (Scheme 5), the N-Boc protected pyrrolidinephosphine 17 [23], with a 2,3-cis configuration in the pyrrolidine backbone, was prepared.…”

“…Although carbohydrates are inexpensive and readily available compounds, relatively abundant in enantiomerically pure form and easily modulated with well-established carbohydrate chemistry, their use as starting materials for the synthesis of organocatalysts remains scarce [21]. We have recently reported [22,23] the synthesis of a novel class of pyrrolidine-based phosphine/phosphinite/aminophosphite ligands from readily available sugars. These compounds were used in the enantioselective Pd-allylic substitution and Ir-catalyzed hydrogenation reactions of minimally functionalized olefins, obtaining excellent enantioselectivities.…”