Synthesis of Chiral (Indol‐2‐yl)methanamines and Insight into the Stereochemistry Protecting Effects of the 9‐Phenyl‐9‐fluorenyl Protecting Group

Abstract

(2015). Synthesis of chiral 2-indolyl methanamines and insight into the stereochemistry protecting effects of the 9-phenyl-9-fluorenyl protecting group. EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2015(17) Keywords: Asymmetric synthesis / Amino acids / Chiral pool / Protecting groups Tetrahydro-β-carbolines, a privileged structural feature in natural products and pharmaceutically active compounds, has been the cause for considerable research interest, spanning many decades. Herein is reported the synthesis of the structurally closely related compounds denoted as (indol-2-yl)methanamines, in 99 % ee using amino acid starting materials, coupled with a 9-phenyl-9-fluorenyl (Pf) protect-

Mild, Rapid, and Chemoselective Procedure for the Introduction of the 9-Phenyl-9-fluorenyl Protecting Group into Amines, Acids, Alcohols, Sulfonamides, Amides, and Thiols

“…However, if the equiv of AgNO 3 was increased to 2.4, then, 25 was obtained in excellent yield after 30 min. Alternatively, converting the hydrochloride salt to the free amine via a base wash and then subjecting it to our usual conditions also gave 25 in excellent yield after 30 min …”

Enantiospecific gram scale synthesis of (S)-eleagnine

“…20 Morpholine amide 2 was obtained by treating methyl ester 1 with morpholine in the presence of t-BuMgCl. Pure product was obtained by trituration from Et 2 O to give>20 g of 2 in 91% yield.…”

An automated computational approach to kinetic model discrimination and parameter estimation

“…Pf is a pharmaceutically relevant and bulky protecting group, that can be introduced as a more acid stable alternative to the more commonly used trityl group. 42,43 This case study is the protection step involved in the total synthesis of (S)-eleagnine from L-alanine. Therefore, understanding this transformation by performing kinetic analysis would lower costs and accelerate process development in the overall bioactive alkaloid manufacture, 44 following promising reports of potent analgesic properties.…”