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Fast‐Synthesis of α‐Phosphonyloxy Ketones as Drug Scaffolds in a Capillary Microreactor
Author(s) -
Ramanjaneyulu Bandaru T.,
Vidyacharan Shinde,
Yim Se Jun,
Kim DongPyo
Publication year - 2019
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201901655
Subject(s) - chemistry , microreactor , formic acid , ketone , combinatorial chemistry , flow chemistry , benzoin , oxazole , microfluidics , organic chemistry , nanotechnology , catalysis , materials science
A simple, room temperature approach for the fast single‐step synthesis of α‐phosphonyloxy ketone, a drug scaffold, has been developed which involves highly reactive species i.e., 1,2‐dicarbonyls that readily react with trialkyl phosphites and formic acids in batch as well as in continuous‐flow with the flow rate of 3 ml/min ( t R = ∼4 s). The present approach reduced the synthesis time from hours to minutes in batch, which was further lowered to a few seconds precisely controlled by single capillary microfluidics. A wide range of 1,2‐dicarbonyl derivatives were smoothly transformed to their corresponding α‐phosphonyloxy ketones in moderate to good yields (50–82 %) under optimized flow‐reaction conditions. Further, the α‐phosphonyloxy ketones produced can be utilized in batch process to form benzoin, oxazole core, and α,α′‐diarylated carbonyl compounds in 82 %, 50 %, and 54 % yields, respectively, which are alternative key precursors/scaffolds of natural products and active pharmaceutical ingredients (APIs).