Cowan, David J.; Collins, Jon L.; Mitchell, Mark B.; Ray, John A.; Sutton, Peter W.; Sarjeant, Amy A.; Boros, Eric E. published their research in Journal of Organic Chemistry on December 20 ,2013. The article was titled 《Enzymatic- and Iridium-Catalyzed Asymmetric Synthesis of a Benzothiazepinylphosphonate Bile Acid Transporter Inhibitor》.HPLC of Formula: 1156547-61-3 The article contains the following contents:
A synthesis of the benzothiazepine phosphonic acid 3 (shown as I), employing both enzymic and transition metal catalysis, is described. The quaternary chiral center of 3 was obtained by resolution of Et (2-ethyl)norleucinate (4) with porcine liver esterase (PLE) immobilized on Sepabeads. The resulting (R)-amino acid (H2N)(HOOC)C(Bu)(Et) (5) was converted in two steps to aminosulfate (Bu)(Et)C(NH2)(CH2OSO3) (7), which was used for construction of the benzothiazepine ring. Benzophenone, 2-benzoyl-5-(bromomethyl)-4-methoxyphenyl trifluoromethanesulfonate (15), prepared in four steps from trimethylhydroquinone, 1,4-(MeO)2-2-MeC6H3 (11), enabled sequential incorporation of P (Arbuzov chem.) and S (Pd(0)-catalyzed thiol coupling) leading to mercaptan intermediate, di-Et 4-benzoyl-5-mercapto-2-methoxybenzylphosphonate (18). S-Alkylation of 18 with aminosulfate 7 followed by cyclodehydration afforded the corresponding dihydrobenzothiazepine. Ir-catalyzed asym. hydrogenation of this dihydrobenzothiazepine with the complex of [Ir(COD)2BArF] (26, BArF = [B(C6H3(CF3)2-3,5)4]) and Taniaphos ligand afforded the corresponding (3R,5R)-tetrahydrobenzothiazepine following flash chromatog. Oxidation of the tetrahydrobenzothiazepine to the corresponding sulfone and phosphonate hydrolysis completed the synthesis of 3 in 12 steps and 13% overall yield. The results came from multiple reactions, including the reaction of (1S)-1-(Dicyclohexylphosphino)-2-[(R)-[2-(dicyclohexylphosphino)phenyl](dimethylamino)methyl]ferrocene(cas: 1156547-61-3HPLC of Formula: 1156547-61-3)
(1S)-1-(Dicyclohexylphosphino)-2-[(R)-[2-(dicyclohexylphosphino)phenyl](dimethylamino)methyl]ferrocene(cas: 1156547-61-3) belongs to chiral phosphine ligands. Nucleophilic phosphine catalysis often involves the formation of Lewis adducts, namely phosphonium (di)enolate zwitterions, as reaction intermediates. HPLC of Formula: 1156547-61-3 These intermediates are formed through nucleophilic attack of the phosphine catalysts at electron-poor nuclei (normally carbon atoms) and then proceed through several steps to form new chemical bonds.
Referemce:
Phosphine ligand,
Chiral phosphines in nucleophilic organocatalysis