Carbohydrate Phosphinites as Practical Ligands in Asymmetric Catalysis:  Electronic Effects and Dependence of Backbone Chirality in Rh-Catalyzed Asymmetric Hydrogenations. Synthesis of R- or S-Amino Acids Using Natural Sugars as Ligand Precursors

Abstract

Vicinal diarylphosphinites derived from carbohydrates are excellent ligands for the Rh(I)-catalyzed enantioselective asymmetric hydrogenation of dehydroamino acid derivatives, producing the highest enantioselectivity of any ligands directly prepared from natural products. The enantioselectivity can be enhanced by the appropriate choice of substituents on the aromatic rings of the phosphinites. For example, the use of phosphinites with electron-donating bis(3,5-dimethylphenyl) groups on phosphorus provides ee's up to 99% for a wide range of amino acids including some with easily removable N-protecting groups. Electron-withdrawing aryl substituents, on the other hand, decrease the enantioselectivity. Sense of chiral induction in the amino acid product depends on the relative juxtaposition of the vicinal diphosphinites on a given sugar backbone. When readily available d-glucopyranosides are used as the starting sugars, 2,3-phosphinites give the S-amino acids and 3,4-phosphinites give the R-amino acids. In the case of aromatic and heteroaromatic amino acids, enantioselectivities > 95% are consistently obtained. Practical considerations such as the ease of ligand synthesis, rates of reactions, catalyst turnover, and scope and limitations in terms of substrates are discussed. A possible explanation for the enhancement of enantioselectivity by electron-rich phosphinites is offered.

Efficient Activation of 2‐Iminomethylpyridine/Cobalt‐Based Alkyne [2+2+2] Cycloaddition Catalyst by Addition of a Silver Salt

“…on reaction efficiency and selectivity, [11] the reason why silver salts other than AgOTf and AgSbF 6 were less effective in the present catalysis is unclear at this stage.…”

Chiral Ionic Phosphites and Diamidophosphites: A Novel Group of Efficient Ligands for Asymmetric Catalysis

“…[21,22] Dimethyl malonate, BSA [N,O-bis(trimethylsilyl)acetamide] and sodium p-toluenesulfinate were commercially available. [PdA C H T U N G T R E N N U N G (allyl)Cl] 2 , [22] [acacRh(CO) 2 ] [23] and [RhA C H T U N G T R E N N U N G (COD) 2 ]BF 4 [24] on the H 3 PW 12 O 40 / SiO 2 support [11a,f] were synthesized using literature procedures. Rhodium(I) complex 2 was synthesized for the 31 P NMR and IR experiments in chloroform, analogously to the known procedures.…”

Asymmetric Catalytic Reactions Using P*‐Mono‐, P*,N‐ and P*,P*‐Bidentate Diamidophosphites with BINOL Backbones and 1,3,2‐Diazaphospholidine Moieties: Differences in the Enantioselectivity

“…[26][27][28] Starting substrates (E)-1,3-diphenylallyl acetate 8, ethyl (E)-1,3-diphenylallyl carbonate 10 and cyclohex-2-enyl ethyl carbonate 12 were synthesized as published. [26,29,30] (S a )-and (R a )-2,2'-dihydroxy-1,1'-binaphthyls (S a )-1 and (R a )-1, sodium para-toluenesulfinate, dimethyl malonate, BSA [N,O-bis(trimethylsilyl)acetamide] and starting substrates dimethyl itaconate 14a and methyl 2-acetamidoacrylate 14b were purchased from Aldrich and Acros Organics and used without further purification.…”