Strained Azetidinium Ylides:  New Reagents for Cyclopropanation

Abstract

Azetidinium ylides showed a remarkable ability to perform the cyclopropanation of Michael acceptors. Ephedrine-derived azetidinium ylides allowed the formation of substituted cyclopropanes in good yields and at a high level of stereoselectivity. The determination of the relative stereochemistries in the produced cyclopropanes gave some insight into the reaction mechanism.

Aziridine- and Azetidine-Pd Catalytic Combinations. Synthesis and Evaluation of the Ligand Ring Size Impact on Suzuki-Miyaura Reaction Issues

“…The coupling between 4-bromonitrobenzene and 4-tolylboronic acid was chosen as the model coupling reaction (Scheme 4). Gratifyingly, running the reaction at room temperature for 10 h, using 1% of catalytic loading and base/solvent combination (Cs2CO3 and DMF/H2O) as already reported for benzhydrylamines [20][21][22][23][24], allowed us to identify 4-nitro-4′-methyl biphenyl 5 in the crude material 1 H NMR spectra. Various conversions were observed ranging from 10% to 50% evidencing that our catalytic systems were able to trigger Suzuki-Miyaura coupling at room temperature.…”

“…Column chromatography separations were performed using silica gel (0.040-0.060 mm). (N-benzyl)-2-cyanoazetidine 1 and (N-benzyl)-2-cyanoaziridine 2 have been prepared according to references [24,25].…”

“…Cyanoazetidine 1 and cyanoaziridine 2 have been easily obtained in two and three steps respectively starting from commercially available reactants as reported earlier [24,25]. The further step was to prepare vicinal diamines 3 and 4.…”

Alkylation/elimination from azetidinium ylides: an entry to functionalized acrylonitriles

“…We have previously demonstrated that these species react with carbonyl compounds to give, after nucleophilic addition and subsequent intramolecular substitution, the corresponding amino epoxides 2, 2 while reaction with Michael acceptors leads to functionalized cyclopropanes 3. 3 In this Letter, we demonstrate further utility of these ylides by reacting them with primary halides, which leads, after a consecutive Hofmann elimination, to the corresponding functionalized alkenes 4. (Scheme 1) 2-Cyanoazetidinium salts 5-7 shown in Figure 1 were selected in order to examine the scope of this sequence by varying the nature of the substituents on the nitrogen atom near to the reacting center.…”

“…First was examined the conjugate addition of azetidinium ylide derived from 5 on 13. 3 Thus, the ylide produced by treatment with LiHMDS reacted in good yield with 13 to afford 25 in 85% de (two minors stereoisomers could be detected in the purified product, representing 4 and 11% respectively of the diastereoisomeric mixture). The absolute configuration of the quaternary stereocenters in the major isomer was assigned on the basis of previous examples 3 and relative configuration was tentatively assigned considering the magnetic equivalency of the protons on the cyclopropane ring, which appear as a singlet (Scheme 6).…”