Achmatowicz reaction

The Achmatowicz Reaction is an organic synthesis in which a furan is converted to a dihydropyran. In the original publication by Osman Achmatowicz Jr. in 1971 ["Synthesis of methyl 2,3-dideoxy--alk-2-enopyranosides from furan compounds : A general approach to the total synthesis of monosaccharides" Tetrahedron, Volume 27, Issue 10, 1971, Pages 1973-1996 O. Achmatowicz, P. Bukowski, B. Szechner, Z. Zwierzchowska and A. Zamojski DOI|10.1016/S0040-4020(01)98229-8] furfuryl alcohol is reacted with bromine in methanol to "2,5-dimethoxy-2,5-dihydrofuran" which rearranges to the dihydropyran with dilute sulfuric acid. Additional reaction steps, alcohol protection with methyl orthoformate and boron trifluoride) and ketone reduction with sodium borohydride produce an intermediate from which many monosaccharides can be synthesised.

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The Achmatowitz protocol has been used in total synthesis for example that of "desoxoprosophylline" ["Asymmetric total synthesis of (+)-desoxoprosophylline" Tetrahedron Letters, Volume 39, Issue 50, 10 December 1998, Pages 9227-9228 Cui-Fen Yang, Yi-Ming Xu, Li-Xin Liao and Wei-Shan Zhou DOI|10.1016/S0040-4039(98)02129-7 ] , "Pyrenophorin" ["Efficient Conditions for Conversion of 2-Substituted Furans into 4-Oxygenated 2-Enoic Acids and Its Application to Synthesis of (+)-Aspicilin, (+)-Patulolide A, and (-)-Pyrenophorin" Kobayashi, Y.; Nakano, M.; Kumar, G. B.; Kishihara, K. J. Org. Chem.; (Article); 1998; 63(21); 7505-7515. DOI|10.1021/jo980942a ] and "Bao Gong Teng A" ["Organometallic Enantiomeric Scaffolding: Organometallic Chirons. Total Synthesis of (-)-Bao Gong Teng A by a Molybdenum-Mediated [5+2] Cycloaddition"Yongqiang Zhang and Lanny S. Liebeskind J. Am. Chem. Soc. 2006; 128(2) pp 465 - 472; (Article) DOI|10.1021/ja055623x] . Very recently it has been used in diversity oriented synthesis ["A Synthesis Strategy Yielding Skeletally Diverse Small Molecules Combinatorially" Martin D. Burke, Eric M. Berger, and Stuart L. Schreiber J. Am. Chem. Soc. 126 (43), 14095 -14104, 2004. DOI|10.1021/ja0457415 ] [Reagents: NBS, PPTS, for macrobeads see: solid-phase synthesis]

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and in enantiomeric scaffolding ["Practical, Scalable, High-Throughput Approaches to 3-Pyranyl and 3-Pyridinyl Organometallic Enantiomeric Scaffolds Using the Achmatowicz Reaction" Thomas C. Coombs, Maurice D. Lee, IV, Heilam Wong, Matthew Armstrong, Bo Cheng, Wenyong Chen, Alessandro F. Moretto, and Lanny S. Liebeskind J. Org. Chem. 73 (3), 882 -888, 2008. DOI|10.1021/jo702006z] [Reagents: benzyl chloroformate protects amine as Cbz group, Achmatowitz reaction with m-CPBA, complexation with a molybdenum compound, Cp is cyclopentadienyl] .

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References