Premium
Streamlined Asymmetric Reaction Development: A Case Study with Isatins
Author(s) -
Thanzeel F. Yushra,
Balaraman Kaluvu,
Wolf Christian
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201902688
Subject(s) - yield (engineering) , throughput , computer science , reaction conditions , frame (networking) , combinatorial chemistry , process engineering , chemistry , organic chemistry , catalysis , materials science , engineering , telecommunications , metallurgy , wireless
Asymmetric reaction development within a day or two has been a dream of synthetic chemists for several decades. We now show that such a task is feasible with a highly efficient streamlined screening strategy using the asymmetric allylation of isatins with a chiral boron complex as a case study. Our high‐throughput screening (HTS) method is based on fast optical UV/CD analysis of minute amounts of crude reaction mixtures (≈3 mg scale) and it obviates product isolation and the general need for reference compounds which greatly reduces preliminary work and analysis time. The setup, reaction screening, analysis and data processing for 54 asymmetric allylations of nine different isatins in six different solvents was handled by a single operator in less than 20 work hours. One could easily extend this HTS strategy to hundreds of reactions in roughly the same time frame and further reduce the labor with commercially available automated high‐throughput experimentation equipment. The effectiveness of this asymmetric reaction development strategy is confirmed with the upscale synthesis of two representative 3‐allyl‐3‐hydroxyisatins in 98–99 % yield and with 91–94 % ee under optimized conditions.