59192-95-9Relevant academic research and scientific papers
Electrophilic Zinc Homoenolates: Synthesis of Cyclopropylamines from Cyclopropanols and Amines
Mills, L. Reginald,Barrera Arbelaez, Luis Miguel,Rousseaux, Sophie A. L.
, p. 11357 - 11360 (2017)
Metal homoenolates, produced via C-C bond cleavage of cyclopropanols, have been extensively investigated as nucleophiles for the synthesis of β-substituted carbonyl derivatives. Herein, we demonstrate that zinc homoenolates can react as carbonyl-electrophiles in the presence of nucleophilic amines to yield highly valuable trans-cyclopropylamines in good yields and high diastereoselectivities. GSK2879552, a lysine demethylase 1 inhibitor currently in clinical trials for the treatment of small cell lung carcinoma, was synthesized using this strategy.
Synthesis of trans-2-Substituted Cyclopropylamines from α-Chloroaldehydes
West, Michael S.,Mills, L. Reginald,McDonald, Tyler R.,Lee, Jessica B.,Ensan, Deeba,Rousseaux, Sophie A. L.
, p. 8409 - 8413 (2019/10/14)
Cyclopropylamines are prevalent in pharmaceuticals and agrochemicals. Herein, we report the synthesis of trans-2-substituted cyclopropylamines in high diastereoselectivity from readily available α-chloroaldehydes. The reaction proceeds via trapping of an electrophilic zinc homoenolate with an amine followed by ring closure to generate the cyclopropylamine. We have also observed that cyclopropylamine cis/trans-isomerization occurs in the presence of zinc halide salts and that this process can be turned off by the addition of a polar aprotic cosolvent.
