Thiol-Free Synthesis of Oseltamivir and Its Analogues via Organocatalytic Michael Additions of Oxyacetaldehydes to 2-Acylaminonitroalkenes

Juraj Rehák; Martin Huťka; Attila Latika; Henrich Brath; Ambroz Almássy; Viktória Hajzer; Július Durmis; Štefan Toma; Radovan Šebesta

doi:10.1055/s-0031-1290396

Synthesis, Inhaltsverzeichnis

Synthesis 2012; 44(15): 2424-2430
DOI: 10.1055/s-0031-1290396

paper

Thiol-Free Synthesis of Oseltamivir and Its Analogues via Organocatalytic Michael Additions of Oxyacetaldehydes to 2-Acylaminonitroalkenes

Juraj Rehák

^aSynkola Ltd., Mlynska dolina CH-2, 84215 Bratislava, Slovak Republic

,

Martin Huťka

^bDepartment of Organic Chemistry, Faculty of Natural Sciences, Comenius University, Mlynska dolina CH-2, 84215 Bratislava, Slovak Republic, Fax: +421(2)60296337 eMail: radovan.sebesta@fns.uniba.sk

,

Attila Latika

^aSynkola Ltd., Mlynska dolina CH-2, 84215 Bratislava, Slovak Republic

,

Henrich Brath

^aSynkola Ltd., Mlynska dolina CH-2, 84215 Bratislava, Slovak Republic

,

Ambroz Almássy

^bDepartment of Organic Chemistry, Faculty of Natural Sciences, Comenius University, Mlynska dolina CH-2, 84215 Bratislava, Slovak Republic, Fax: +421(2)60296337 eMail: radovan.sebesta@fns.uniba.sk

,

Viktória Hajzer

^aSynkola Ltd., Mlynska dolina CH-2, 84215 Bratislava, Slovak Republic

,

Július Durmis*

^aSynkola Ltd., Mlynska dolina CH-2, 84215 Bratislava, Slovak Republic

,

Štefan Toma

^bDepartment of Organic Chemistry, Faculty of Natural Sciences, Comenius University, Mlynska dolina CH-2, 84215 Bratislava, Slovak Republic, Fax: +421(2)60296337 eMail: radovan.sebesta@fns.uniba.sk

,

Radovan Šebesta*

^bDepartment of Organic Chemistry, Faculty of Natural Sciences, Comenius University, Mlynska dolina CH-2, 84215 Bratislava, Slovak Republic, Fax: +421(2)60296337 eMail: radovan.sebesta@fns.uniba.sk

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Abstract

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Abstract

The organocatalytic addition of substituted oxyacetaldehydes to 2-acylaminonitroethenes proceeded with good to high diastereoselectivities and enantioselectivities. The resulting adducts reacted with ethyl 2-(diethoxyphosphoryl) acrylate to afford highly functionalized cyclohexenes. A thiol-free protocol for cyclization has been developed that leads to a separable mixture of two diastereoisomers. The unwanted diastereoisomer can be efficiently epimerized. The resulting cyclohexenes are precursors to oseltamivir and its analogues. The synthesis of the key reagent, 3-pentyloxyaldehyde, was also improved.

Key words

enantioselectivity - Michael addition - cyclization - aminonitroethene - organocatalysis

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Referenzen

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