Achmatowicz reaction

Achmatowicz reaction
Named after	Osman Achmatowicz Jr.
Reaction type	Rearrangement reaction
Identifiers
RSC ontology ID	RXNO:0000233

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The Achmatowicz reaction, also known as the Achmatowicz rearrangement, is an organic synthesis in which a furan is converted to a dihydropyran. In the original publication by the Polish chemist Osman Achmatowicz Jr. (b. 20 December 1931 in Vilnius) in 1971 ^[1] 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 then ketone reduction with sodium borohydride produce an intermediate from which many monosaccharides can be synthesised.

The Achmatowitz protocol has been used in total synthesis, including those of desoxoprosophylline,^[2] pyrenophorin ^[3]^[4] Recently it has been used in diversity oriented synthesis^[5]^[6]

and in enantiomeric scaffolding.^[7]^[8]

References

^ Achmatowicz, O.; Bukowski, P.; Szechner, B.; Zwierzchowska, Z.; Zamojski, A. (1971-01-01). "Synthesis of methyl 2,3-dideoxy-DL-alk-2-enopyranosides from furan compounds: A general approach to the total synthesis of monosaccharides". Tetrahedron. 27 (10): 1973–1996. doi:10.1016/S0040-4020(01)98229-8. ISSN 0040-4020.
^ Yang, Cui-Fen; Xu, Yi-Ming; Liao, Li-Xin; Zhou, Wei-Shan (1998-12-10). "Asymmetric total synthesis of (+)-desoxoprosophylline". Tetrahedron Letters. 39 (50): 9227–9228. doi:10.1016/S0040-4039(98)02129-7. ISSN 0040-4039.
^ Kobayashi, Yuichi; Nakano, Miwa; Kumar, G. Biju; Kishihara, Kiyonobu (1998-10-01). "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". The Journal of Organic Chemistry. 63 (21): 7505–7515. doi:10.1021/jo980942a. ISSN 0022-3263. PMID 11672404.
^ Zhang, Yongqiang; Liebeskind, Lanny S. (2006-01-01). "Organometallic Enantiomeric Scaffolding: Organometallic Chirons. Total Synthesis of (−)-Bao Gong Teng A by a Molybdenum-Mediated [5+2] Cycloaddition". Journal of the American Chemical Society. 128 (2): 465–472. doi:10.1021/ja055623x. ISSN 0002-7863. PMID 16402833.
^ Reagents: NBS, PPTS, for macrobeads see: solid-phase synthesis
^ Burke, Martin D.; Berger, Eric M.; Schreiber, Stuart L. (2004-11-01). "A Synthesis Strategy Yielding Skeletally Diverse Small Molecules Combinatorially". Journal of the American Chemical Society. 126 (43): 14095–14104. doi:10.1021/ja0457415. ISSN 0002-7863. PMID 15506774.
^ Coombs, Thomas C.; Lee; Wong, Heilam; Armstrong, Matthew; Cheng, Bo; Chen, Wenyong; Moretto, Alessandro F.; Liebeskind, Lanny S. (2008-02-01). "Practical, Scalable, High-Throughput Approaches to η3-Pyranyl and η3-Pyridinyl Organometallic Enantiomeric Scaffolds Using the Achmatowicz Reaction". The Journal of Organic Chemistry. 73 (3): 882–888. doi:10.1021/jo702006z. ISSN 0022-3263. PMC 2652699. PMID 18171075.
^ Reagents: benzyl chloroformate protects amine as Cbz group, Achmatowitz reaction with m-CPBA, complexation with a molybdenum compound, Cp is cyclopentadienyl anion

[1] Achmatowicz, O.; Bukowski, P.; Szechner, B.; Zwierzchowska, Z.; Zamojski, A. (1971-01-01). "Synthesis of methyl 2,3-dideoxy-DL-alk-2-enopyranosides from furan compounds: A general approach to the total synthesis of monosaccharides". Tetrahedron. 27 (10): 1973–1996. doi:10.1016/S0040-4020(01)98229-8. ISSN 0040-4020.

[2] Yang, Cui-Fen; Xu, Yi-Ming; Liao, Li-Xin; Zhou, Wei-Shan (1998-12-10). "Asymmetric total synthesis of (+)-desoxoprosophylline". Tetrahedron Letters. 39 (50): 9227–9228. doi:10.1016/S0040-4039(98)02129-7. ISSN 0040-4039.

[3] Kobayashi, Yuichi; Nakano, Miwa; Kumar, G. Biju; Kishihara, Kiyonobu (1998-10-01). "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". The Journal of Organic Chemistry. 63 (21): 7505–7515. doi:10.1021/jo980942a. ISSN 0022-3263. PMID 11672404.

[4] Zhang, Yongqiang; Liebeskind, Lanny S. (2006-01-01). "Organometallic Enantiomeric Scaffolding: Organometallic Chirons. Total Synthesis of (−)-Bao Gong Teng A by a Molybdenum-Mediated [5+2] Cycloaddition". Journal of the American Chemical Society. 128 (2): 465–472. doi:10.1021/ja055623x. ISSN 0002-7863. PMID 16402833.

[5] Reagents: NBS, PPTS, for macrobeads see: solid-phase synthesis

[6] Burke, Martin D.; Berger, Eric M.; Schreiber, Stuart L. (2004-11-01). "A Synthesis Strategy Yielding Skeletally Diverse Small Molecules Combinatorially". Journal of the American Chemical Society. 126 (43): 14095–14104. doi:10.1021/ja0457415. ISSN 0002-7863. PMID 15506774.

[7] Coombs, Thomas C.; Lee; Wong, Heilam; Armstrong, Matthew; Cheng, Bo; Chen, Wenyong; Moretto, Alessandro F.; Liebeskind, Lanny S. (2008-02-01). "Practical, Scalable, High-Throughput Approaches to η3-Pyranyl and η3-Pyridinyl Organometallic Enantiomeric Scaffolds Using the Achmatowicz Reaction". The Journal of Organic Chemistry. 73 (3): 882–888. doi:10.1021/jo702006z. ISSN 0022-3263. PMC 2652699. PMID 18171075.

[8] Reagents: benzyl chloroformate protects amine as Cbz group, Achmatowitz reaction with m-CPBA, complexation with a molybdenum compound, Cp is cyclopentadienyl anion

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