A.E.Favorskii’s scientific legacy in modern organic chemistry: prototropic acetylene – allene isomerization and the acetylene zipper reaction

Abstract

Alexei Evgrafovich Favorskii was an outstanding organic chemist who left a great scientific legacy as a result of long time and fruitful work. Most of the theoretically and practically important discoveries of A.E.Favorskii were made in the chemistry of acetylene and its derivatives. Nowadays, the reactions discovered by him, which include acetylene – allene isomerization, the Favorskii and retro-Favorskii reactions, the Favorskii rearrangement and the vinylation reaction, are widely used in industry and in laboratory synthesis. This review summarizes the main scientific achievements of A.E.Favorskii, as well as their development in modern organic chemistry. Much consideration is given to acetylene – allene isomerization as a convenient method for the synthesis of methyl-substituted acetylenes and to the acetylene zipper reaction as a synthetic tool for obtaining terminal acetylenes. The review presents examples of the application of these reactions in modern organic synthesis of complex molecules, including natural compounds and their analogues. The bibliography includes 266 references.

Design and Synthesis of New 5-aryl-4-Arylethynyl-1H-1,2,3-triazoles with Valuable Photophysical and Biological Properties

“…The effectiveness of this approach was shown previously in our research group [ 35 ]. At the first stage, 2,7-dimethylocta-3,5-diyne-2,7-diol 1 was subjected to retro-Favorskii reaction by the heating with K 2 CO 3 [ 36 , 37 ] to synthesize 2-methylhexa-3,5-diyn-2-ol 2, which was subjected to Sonogashira coupling with iodoarenes 3a – c [ 38 ]. Obtained compounds 4a – c were involved in retro-Favorskii reaction again using KOH.…”

Improved Rigidin-Inspired Antiproliferative Agents with Modifications on the 7-Deazahypoxanthine C7/C8 Ring Systems

“…Disconcertedly, close inspection of the NMR spectra of product ( 27 ) revealed the presence of unexpected signals, not entirely supporting the structure. Although the HRMS obtained (467.2078 amu obtained, expected 467.2083 amu) supported the required molecular formula, examination of the NMR spectra indicated that what we had in hand was a compound in which the alkyne had isomerized into the thermodynamically favored internal position (see Scheme c for structure of actual compound 30 ) . Examination of compound 30 ’s 1 H NMR spectrum showed all the pyrrolo[2,3- d ]pyrimidine core signals, together with the morpholine methylene signals.…”

“…These two alterations effectively resulted in the internalization of the alkyne, a process which was further verified during the synthesis of analogue 31 . In retrospect, the distinctive proton signals supporting alkyne internalization suggests that the C7 para -morpholine sample 15 also contains a fraction (approximately 25% as determined from 1 H spectra integration) of its internal alkyne isomer . Notably, solubilization of pyrrole 12 required only a small volume of DMSO without further temperature increase, thereby resulting in alkyne internalization to a much lesser extent.…”

“…Although the HRMS obtained (467.2078 amu obtained, expected 467.2083 amu) supported the required molecular formula, examination of the NMR spectra indicated that what we had in hand was a compound in which the alkyne had isomerized into the thermodynamically favored internal position (see Scheme 4 c for structure of actual compound 30 ). 42 Examination of compound 30 ’s 1 H NMR spectrum showed all the pyrrolo[2,3- d ]pyrimidine core signals, together with the morpholine methylene signals. However, a distinct change in the alkyne alkyl signals was evident.…”

Copper-catalyzed deacetonative Sonogashira coupling

“…Tertiary propargyl alcohols capable of undergoing a base-mediated C–C bond cleavage (the retro-Favorskii reaction 33 ) are easy to store and inexpensive precursors of terminal alkynes. 34 Several groups evaluated these substrates in the tandem deacetonative Sonogashira coupling under Pd catalysis (Scheme 1C).…”