An Efficient One‐Pot Synthesis of Chiral N‐Protected 3‐Substituted (Diketo)piperazines via Ugi‐4CR/De‐Boc/Cyclization Process. Issue 4 (25th January 2018)

• Record Type: Journal Article
• Authors: Jida, Mouhamad; Ballet, Steven
• Is Part Of: ChemistrySelect. Volume 3:Issue 4(2018)
• Page Start: 1027
• Page End: 1031
• Publication Date: 2018-01-25
• Subjects: Combinatorial chemistry -- Chiral Diketo(piperazines) -- Cialis -- One-pot synthesis -- Ugi-4CR; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201702943
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: A convenient and high yielding method to prepare a vast array of enantiomerically pure 3‐substituted diketopiperazines (3‐DKPs), bearing a benzyl protecting group on nitrogen 1 is reported. The methodology describes a simple one‐pot procedure, starting from readily available N‐protected L‐ or D‐amino acids employing the Ugi‐4CR in pure water, followed by a one‐step Boc‐deprotection and final lactamisation in acetic acid. All disubstituted DKPs were obtained in short times and isolated in excellent yields (84‐94%) by simple precipitation in water and subsequent filtration. The practical utility of this procedure proved efficient for the synthesis of cialis (Tadalafil) analogues. Abstract : A simple and green one‐pot strategy is developed to access a library of chiral N ‐protected‐ 3‐substituted (diketo)piperazines in excellent yields and high enantioselectivity. The methodology describes a simple one‐pot procedure, starting from readily available N‐protected L‐ or D‐amino acids employing the Ugi‐4CR in pure water, followed by a one‐step Boc‐deprotection and final lactamisation in acetic acid. The practical utility of this procedure proved efficient for the synthesis of cialis (Tadalafil) analogues.