Asymmetric Aminolytic Kinetic Resolution of Racemic Epoxides Using Recyclable Chiral Polymeric Co(III)-Salen Complexes: A Protocol for Total Utilization of Racemic Epoxide in the Synthesis of (R)‑Naftopidil and (S)‑Propranolol

• Published in: Journal of organic chemistry Vol. 78; no. 18; pp. 9076 - 9084
• Main Authors: Kumar, Manish, Kureshy, Rukhsana I, Shah, Arpan K, Das, Anjan, Khan, Noor-ul H, Abdi, Sayed H. R, Bajaj, Hari C
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 20.09.2013; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Cobalt - chemistry; Epoxy Compounds - chemistry; Ethylenediamines - chemistry; Kinetics; Molecular Structure; Naphthalenes - chemical synthesis; Naphthalenes - chemistry; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Physical Sciences; Piperazines - chemical synthesis; Piperazines - chemistry; Propranolol - chemical synthesis; Propranolol - chemistry; Science & Technology; Stereoisomerism; CATALYTIC SYNTHESIS; ENANTIOSELECTIVE EPOXIDATION; PROPRANOLOL; PRONETHALOL; DERIVATIVES; ADRENERGIC BLOCKING-AGENTS
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo4012656

Chiral polymeric Co­(III) salen complexes with chiral ((R)/(S)-BINOL, diethyl tartrate) and achiral (piperazine and trigol) linkers with varying stereogenic centers were synthesized for the first time and used as catalysts for aminolytic kinetic resolution (AKR) of a variety of terminal epoxides and glycidyl ethers to get enantio-pure epoxides (ee, 99%) and N-protected β-amino alcohols (ee, 99%) with quantitative yield in 16 h at RT under optimized reaction conditions. This protocol was also used for the synthesis of two enantiomerically pure drug molecules (R)-Naftopidil (α1-blocker) and (S)-Propranolol (β-blocker) as a key step via AKR of single racemic naphthylglycidyl ether with Boc-protected isoproylamine with 100% epoxide utilization at 1 g level. The catalyst 1 was successfully recycled for a number of times.