Direct Synthesis of 5-Acyl-3-oxy-4-pyrones Based On Acid-­Catalyzed Acylation of Enaminodiones with Acylbenzotriazoles via Soft Enolization

A novel convenient acid-catalyzed acylation of enaminodiones with acylbenzotriazoles via soft enolization has been developed for the direct synthesis of hard-to-reach 5-acyl-3-oxy-4-pyrones. The important advantages of the reaction include broad substrate scope, mild conditions, scalability, and readily isolation of products by crystallization without the use of chromatography. Further modification of the pyrone ring and synthesis of various azaheterocycles via ring-opening transformation have been demonstrated for the preparation of potential scaffolds for inhibition of metalloenzymes.

C–C Bond Construction: The Zhu Synthesis of Goniomitine

Non-enolizable β-keto esters such as 3 are fragile and difficult to prepare. Karl J. Hale of Queen’s University Belfast devised (Org. Lett. 2013, 15, 370) soft enolization con­ditions for methoxycarbonylation of 1 with 2. Zheng Huang of the Shanghai Institute of Organic Chemistry coupled (Org. Lett. 2013, 15, 1144) 4 with 5 under Ir catalysis to make 6. Tomoya Miura and Masahiro Murakami of Kyoto University combined (Angew. Chem. Int. Ed. 2013, 52, 3883) the diazo precursor 8 with the allylic alco­hol 7 to give 9, the product of Claisen rearrangement. Tsuyoshi Satoh of the Tokyo University of Science showed (Tetrahedron Lett. 2013, 54, 2533) that the combina­tion of the carbenoid 10 with a ketone enolate 11 led to the cyclopropanol (not illus­trated). Jin Kun Cha of Wayne State University found (Org. Lett. 2013, 15, 1780) that such cyclopropanols coupled with an acid chloride 12 under Pd catalysis to give the diketone 13. Christopher J. O’Brien of Dublin City University established (Chem. Eur. J. 2013, 19, 5854) conditions for the catalytic Wittig reaction of 14 with 15 to give 16, with in situ reduction of the phosphine oxide. Amir H. Hoveyda of Boston College showed (Org. Lett. 2013, 15, 1414) that the allene of 17 underwent selective borylation, lead­ing after coupling with 18 to the triene 19. Damian W. Young of the Broad Institute demonstrated (Org. Lett. 2013, 15, 1218) that ring-closing metathesis gave the alkenyl silane 20 with high geometric control. Halogenation to give 21 could then proceed with either retention or inversion of alkene geometry. Jianwei Sun of the Hong Kong University of Science and Technology and Zigang Li of the Shenzen Graduate School of Peking University condensed (J. Am. Chem. Soc. 2013, 135, 4680) the alkyne 22 with 23 to give the trisubstituted alkene 24 with high geometric control. The condensation worked equally well with medium and large ring ethers. Hua-Jian Xu of the Hefei University of Technology combined (Org. Lett. 2013, 15, 1472) the bromo alkyne 25 with the carboxylate 26 to give the nitrile 27.

Direct carbon–carbon bond formation via reductive soft enolization: a syn-selective Mannich addition of α-iodo thioesters

The β-amino carboxylic acid moiety is a key feature of numerous important biologically active compounds.