Asymmetric Synthesis of Structurally Diverse Aminophosphonic Acids by Using Enantiopure N-(p-Tolylsulfinyl)cinnamaldimines as Reagents

作者：Lyzwa Piotr^*; Blaszczyk Jaroslaw; Sieron Leslaw; Mikolajczyk Marian

来源：European Journal of Organic Chemistry, 2013, 2013(11): 2106-2115.

DOI：10.1002/ejoc.201201589

• Synthetic methods
• Asymmetric synthesis
• Diastereoselectivity
• Aminophosphonic acids

We have developed new approaches to diverse enantiopure aminophosphonic acids by using enantiomeric (S)-N-(p-tolylsulfinyl)cinnamaldimine (1) as a single starting material. The synthetic strategy is based on a highly diastereoselective addition reaction of phosphite anion or -phosphonate carbanion to a sulfinimine followed by isolation of the major diastereoisomeric -amino- or -amino adducts and their further conversion to the desired targets through proper transformation of the cinnamylidene moiety. Both diastereoisomerically pure (SS,RC)- and (SS,SC)--amino adducts 2 and 4 obtained were converted under acidic conditions into the unknown enantiomerically pure (R)- and (S)--amino-,-propenylphosphonic acids 3. In the same way, the enantiopure (R)- and (S)--amino-,-butenylphosphonic acids were synthesized from the corresponding (SS,RC)- and (SS,SC)--amino adducts. Starting from the (SS,RC)--amino adduct a new stereoselective synthesis of (R)-2-amino-3-phosphonopropanoic acid (9) has been accomplished in three simple steps (tandem ozonolysis/reduction reaction, oxidation reaction and acidic hydrolysis) in an overall 40% yield. The 3-amino regioisomer of 9 has been prepared from the (SS,RC)--amino adduct 2 through a two-reaction sequence involving a tandem ozonolysis/reduction reaction and a Mitsunobu cyanation/acidic hydrolysis. The overall yield of this conversion to 11 was 52.5%. According to our strategy, we have been able to complete the first synthesis of the enantiopure (R)-phosphoemeriamine 15, which is an unknown phosphonic analogue of emeriamine (aminocarnitine). The conversion of the (SS,RC)--amino adduct 5 into (R)-phosphoemeriamine has been accomplished in five simple synthetic steps (ozonolysis/reduction reaction, mesylation reaction, amination reaction, methylation reaction and acidic hydrolysis) in 24% overall yield. The stereochemistry of the addition of PIII-nucleophiles and -phosphonate carbanion to a chiral sulfinimine is also discussed.

• 出版日期2013-4