Abstract:A variety of cyclopropylphosphonates were prepared in moderate to good yields by Michael Induced Ring Closure of trialkyl phosphites with the corresponding b-bromoalkylidene cyanoacetates and malonates.
“…Otherwise by using sodium hydride in THF at 0 °C an aza-MIRC (Michael-initiated ring closure) reaction yielded directly aziridines 3a , b (Scheme ) in agreement with our previous findings. 2 Direct Amination Reaction of 1 a − d …”
[reaction: see text] The amination of 2-(trifluoromethyl)acrylates, performed by nosyloxycarbamates, gives two different aminated products, the derivatives of alpha-trifluoromethyl beta-amino esters or the aziridines, in high yields by changing the reaction conditions. The aza-Michael addition product was isolated for the first time in this kind of reaction. This finding confirms the aza-MIRC mechanism we previously proposed. Asymmetric induction was also pursued.
“…Otherwise by using sodium hydride in THF at 0 °C an aza-MIRC (Michael-initiated ring closure) reaction yielded directly aziridines 3a , b (Scheme ) in agreement with our previous findings. 2 Direct Amination Reaction of 1 a − d …”
[reaction: see text] The amination of 2-(trifluoromethyl)acrylates, performed by nosyloxycarbamates, gives two different aminated products, the derivatives of alpha-trifluoromethyl beta-amino esters or the aziridines, in high yields by changing the reaction conditions. The aza-Michael addition product was isolated for the first time in this kind of reaction. This finding confirms the aza-MIRC mechanism we previously proposed. Asymmetric induction was also pursued.
“…1-Cyano-2-(1-ethylpropyl)cyclopropanecarboxylic Acid Methyl Ester 44. To a solution of 2-cyano-4-ethyl-hex-2-enoic acid methyl ester 42 (6.3 g, 35 mmol) in 35 mL of acetonitrile were added nitromethane (3.0 mL, 5 mmol) and then DBU (5.2 mL, 35 mmol), resulting in a red-orange solution. The mixture was heated to reflux 3 h, cooled, and concentrated.…”
As part of a program aimed at generating compounds with affinity for the alpha(2)-delta subunit of voltage-gated calcium channels, several novel beta-amino acids were prepared using an efficient nitroalkane-mediated cyclopropanation as a key step. Depending on the ester that was chosen, the target amino acids could be prepared in as few as three steps. The cyclopropyl amino acids derived from ketones proved to be potent binders of the alpha(2)-delta subunit of voltage-gated calcium channels, but did not interact with the large neutral amino acid system L (leucine) transporter. Anticonvulsant effects were observed in vivo with compound 34 but only after intracerebroventricular (icv) administration, presumably due to inadequate brain concentrations of the drug being achieved following oral dosing. However, pregabalin 1 was active in the DBA/2 model after oral (and icv) dosing, supporting a hypothesis that active transport is a prerequisite for such zwitterionic species to cross the blood-brain barrier.
“…[39] In accordance to this generalisation, Stevens and coworkers showed, that compounds incorporating both a ge-minal double-activated alkene and an allylic halide functionality, react with trialkyl phosphites to give cyclopropanes by a Michael addition-S N 2 tandem reaction. [40] The concept of betains that we have described so far, seems to be quite reasonable and helps to rationalize the different findings. Yet, the actual outcome of a reaction is sometimes difficult to predict and studying the respective literature is sometimes unavoidable.…”
Section: Nucleophiles Of the General Structure R 2 P(orј) Rp(orј) 2 mentioning
Phosphorus is essential for many reagents in organic synthesis, for ligands of late-transition metals and for phosphonoand phosphanylamino acids, the latter being important isosteres of amino acids. Similar to the Michaelis-Arbuzov and the Michaelis-Becker reaction the phospha-Michael addition, i. e. the addition of a phosphorus nucleophile to an acceptor-substituted alkene or alkyne, certainly represents one of the most versatile and powerful tools for the formation of P-C bonds since many different electrophiles and P nu-
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