Furthermore, the $\delta^+$ of the carbonyl carbon might attract nucleophiles, so even if pathway B in your rxn. 18–21. Barton's proposed biosynthesis of (−)-acutumine (3). (A) EncM catalyzed C4 dual oxidation and triggered Favorskii-type rearrangement in enterocin biosynthesis. Chem., 1996, vol. Moreover, at the junction of intermediate D it is also possible to have protonation followed by hydroxide anion attack on the cyclopropanone carbonyl followed by ring opening and loss of hydroxide anion to form product 3. Hypervalent-iodine-induced Favorskii quasi rearrangement by treatment of stereoidal ketones 187 with PhI(OAc)2 and KOH in MeOH proceeded to yield C ring-contraction product 189. 39 732 View the article online for updates and enhancements. Synthesis of a complex guaianolide lactone from (S)-carvone via intermediate 17.2. The Favorskii reaction is an organic chemistry reaction between an alkyne and a carbonyl group, under a basic condition. When this rearrangement is catalyzed by an acid, it is called Meyer–Schuster rearrangement. Of course, I'm referring to different substrates than the one pictured. Chem., 1963, vol. rev 2020.11.24.38066, The best answers are voted up and rise to the top, Chemistry Stack Exchange works best with JavaScript enabled, Start here for a quick overview of the site, Detailed answers to any questions you might have, Discuss the workings and policies of this site, Learn more about Stack Overflow the company, Learn more about hiring developers or posting ads with us. 1, p. 27. The rearrangement is stereospecific as treatment of the isomers 192 and 193 with lithium methoxide in methanol gave two distinct reactions. In the Favorskii rearrangement,379 also called the Wallach degradation, an α-chloroketone (e.g., 2-chlorocyclohexanone) is treated with NaOH under thermodynamic conditions to form the enolate anion 422. These two arguments effectively eliminate pathways C and D from consideration. Treatment of 427 with sodium methoxide gave a 95% yield of the Favorskii rearrangement product (428), obtained as the methyl ester since the reaction was done in methanol. Use MathJax to format equations. and Vasil’ev, A.V., Russ. Soc., 1950, vol. @Greg E One thought your comment about removing the alpha hydrogen attached to the C-Cl carbon generated is why not eliminate that alpha hydrogen and chlorine to form a carbene(oid). The in situ reduction was carried out because of the apparent instability of the aldehydes resulting from the quasi-Favorskii rearrangement.90, The addition of methyllithium to the five-membered ring 208 could be conducted without Favorskii rearrangement to give alcohols 209. Khim. Soc., 2005, vol. The key step in this route is the semibenzylic Favorskii rearrangement of a [4.4.2]propellane keto mesylate 190 to a [4.4.1lpropellane carboxylic acid 191 in 50% aqueous THF solution of LiOH (Scheme 60).85. John Mann, in Comprehensive Organic Synthesis, 1991. Form and we will follow up with your librarian or Institution on your behalf. The computer you are using is not registered by an institution with a subscription to this article. Lett., 2008, vol. Khim. Favorskii Reaction. Enolization occurs on the side of the ketone away from the bromine atom and the enolate cyclizes. Chem., 2010, vol. Asking for help, clarification, or responding to other answers. Pathway A, besides being the only game in town, is actually favored by two factors, 1) as noted above, hydrogen A is acidic and it's removal produces a resonance stabilized carbanion, and 2) completion of the Favorskii reaction is strongly favored by entropic factors since the carbanion and the C-Cl carbon are contained in the same molecule and held relatively close together. 40, p. 2250. We also note that product 4 is the major product when the reaction is carried out in aqueous solution, whereas it is a minor product when the solvent is ethanol. Copyright © 2020 Elsevier B.V. or its licensors or contributors. The authors explain the difference in products obtained under aqueous KOH and ethanolic KOH conditions as having to do with the possible hydrolysis of 1 at the very beginning of the reaction (i.e., SN2 replacement of Cl group by OH group). The energy difference is about $1.5~\mathrm{kcal\cdot{}mol^{-1}}$ (DF-BP86/def2-SVP). Hydrolysis gives the final product, cyclopentanecarboxylic acid. Some cyclic α-halo alcohols and their derivatives under basic conditions also follow the semibenzylic Favorskii rearrangement pathway. The Favorskii Rearrangement To cite this article: A A Akhrem et al Shakhidayatov1970 Russ. What I mean by "I'm referring to different substrates than the one pictured" is that my comments were about alternate reaction pathways for $\alpha$-halo ketones in general in the presence of appropriate nucleophiles/bases, not cyclohexanone specifically. 2 996 552, 1958; Chem. Protsuk, A.I. This reaction can be useful synthetically, as in Ley and coworker's380 synthesis of trilobolide. The bases employed include: hydroxides of Group I and Group II metals; alkoxides, carbonates and hydrogen-carbonates of Group I metals; ammonia, and amines. The further isotope labeling experiments and subsequent high-resolution tandem mass spectrometry of proteinase K-digested EncM have provided convincing evidence for the presence of flavin-N5-oxide.114 Recently, O2-pressurized X-ray crystallography combined with quantum mechanical calculations provide further detailed insight into the positioning of O2 at the reaction site of EncM and illustrate how EncM definitely control the formation of the corresponding flavin-oxygen adduct.115 On the basis of these data, a possible pathway for generation of flavin-N5-oxide was proposed (Fig.