Synthesis of New Pyrroline Nitroxides with Ethynyl Functional Group

Abstract

3-Substituted and 3,4-disubstituted pyrroline nitroxides containing an ethynyl 20 group or two ethynyl groups were achieved by the reaction of a paramagnetic aldehydes with dimethyl (1-diazo-2-oxopropyl)phosphonate (Bestmann-Ohira reagent). The new compounds containing an ethynyl group were found to be useful building blocks in Sonogashira coupling, cyclization, and cycloaddition reactions producing potentially "azido-specific" cross-linking spin labels, paramagnetic ligands, and polyradical scaffolds. 25

Syntheses and Reactions of Pyrroline, Piperidine Nitroxide Phosphonates

“…Qualitative TLC was performed on commercially available plates (20 cm × 20 cm × 0.02 cm) coated with Merck Kieselgel GF 254 . Compounds 1a [19], 1b [20], 1c [21], 3 [22], 5a [33], 5b [23], 6 [25], 9a [34], 9b [20], 9c [21], 15 [40], 18 [46], TEMPO [23] and TEMPOL [23] were synthesized as previously described.…”

“…Thus we obtained compound 17, fortunately without epoxidation of the double bond. The paramagnetic acetylene phosphonate can be prepared by deprotonating acetylene 18 [46] at a terminal acetylene carbon with lithium hexamethyldisilazane (LiHMDS) followed by treatment with diethylchlorophosphate to give compound 19 (Scheme 5). The formation of acetylenephosphonate is proven by the shielded 31 P signal at −6.4 ppm (see Supplementary Materials).…”

Advances in the synthesis of nitroxide radicals for use in biomolecule spin labelling

“…Amongst the most well-established is enyne 66 (Scheme 7b; also known as 'TPA'), which is prepared from alcohol 62 by oxidation to the aldehyde and subsequent alkynylation by the Ohira-Bestmann protocol. 32 The equivalent isoindoline alkyne 67 has been synthesized from iodide 68 by Cu-free Sonogashira crosscoupling with trimethylsilylacetylene. 33 Finally, bioorthogonal strategies are highly attractive from the perspective of achieving intracellular SDSL.…”

“…36 Alternatively, a two-step hydrolysis followed by mono-oxidation gave aldehyde 77; subsequent alkynylation and various manipulations gave bromide 78, azide 79 or MTS 80. 32 Maleimide sidechains equipped with leaving groups enable dual attachment of spin labels. A dibromomaleimide nitroxide Please do not adjust margins Please do not adjust margins 81 (Scheme 9) has been prepared from amide 54 via Hofmann rearrangement to an intermediate amine, then reaction with N-methoxycarbonyldibromomaleimide.…”

Unexpected formation of 2-alkynylpyridines from iodo-selenopyridines by selective activation of C Se over C I bonds

“…In view of this unexpected result (Scheme 1), we focused our studies around the construction of 2-alkynylpyridines derivatives [14][15][16][17][18][19][20][21][22][23][24][25]. In addition, some DFT calculations were performed to enlighten the origin of this result, thus providing mechanistic insights into this access to the alkynylpyridine pattern.…”