244104-72-1

Upstream product

• 623-43-8 crotonic acid methyl ester 
• 146860-26-6 (+)-(R_S)-3-{[(4-methylphenyl)sulfinyl]methyl}-1-oxa-4-azaspiro[4.5]dec-3-ene 
• 1517-82-4 (1R,2S,5R,SS)-(-)-menthyl p-toluenesulfinate 
• 146377-35-7 4-methyl-2,2-pentamethylene-2,5-dihydrooxazole 

Relevant academic research and scientific papers

Straightforward synthesis of [(2S,4R)-1-cyclohexyl-4-methylpiperidin-2-yl] methanol and [(2S,4R)-1-cyclohexyl-4-methylpiperidin-2-yl](diphenyl)methanol: Novel chiral ligands for the catalytic addition of diethylzinc to benzaldehyde to give rise to an extensive turn in the sense of asymmetric induction

Enantiopure [(2S,4R)-1-cyclohexyl-4-methylpiperidin-2-yl]methanol 5a and [(2S,4R)-1-cyclohexyl-4-methylpiperidin-2-yl]-(diphenyl)methanol 5b, new β-amino alcohols based on l-pipecolinic acid (homoproline), have been prepared straightforwardly from rac-alaninol and rac-2-amino-1,1-diphenylpropan- 1-ol, respectively. The described route constitutes as a model procedure for the preparation of other related C(4) or/and C(3)-substituted 2- piperidinylmethanols. The new chiral ligands have shown a singular behaviour on the stereocontrol of the benchmark reaction of benzaldehyde and diethylzinc compared with other C(4)-unsubstituted analogues prepared by ourselves from l-pipecolinic acid (compounds 5c, 5d, 5e and 5f). The catalytic activity, the sense of asymmetric induction and the degree of the enantioselectivity depend on the appropriate combination of the substituents on the structural scaffold, but also on the metal-alkoxide involved in the catalysis (zinc or lithium alkoxides). The enantioselective addition of diethylzinc to benzaldehyde mediated by ligands 5a and 5c has been studied with DFT methods. The theoretical evaluation was performed in connection with a working hypothesis based on the different loadings of cis- and trans-catalysts in the reaction medium.

Diastereoselective synthesis of 3,4-disubstituted 5-(p-tolylsulfinyl)-5,6- dehydropiperidin-2-ones: Chirality transfer in the enantioselective synthesis of ethyl (+)-(3S,4aS,7aS)-1-oxo-octahydro-1H-cyclopenta[c]pyridine-3-carboxylate

The base-mediated reaction of enantiomerically pure α- sulfinylketimine (+)-1 with (E)-α,β-disubstituted propenoate esters afforded 3,4-disubstituted-5-(p-tolylsulfinyl)-5,6-dehydropiperidin-2-ones 9α-13α and 14 with high or complete diastereoselectivity. A sole diastereomer of the four possible ones, with regard to the nature of ester, was isolated, which revealed the stereocontrol of the chiral sulfinyl group in the Michael reaction and transenolization steps. In addition, the enantioselective synthesis of ethyl (+)-(3S,4aS,7aS)-1-oxo-octahydro-1H-cyclopenta[c]pyridine-3- carboxylates (+)-17α is described (five steps; 47% yield; ee ≥97%). The absolute configuration of stereocentres introduced in (+)-17α was assigned on the basis of 1H NMR data.

Diastereoselective synthesis of 4-substituted 5-(p-tolylsulfinyl)-5,6-dehydropiperidin-2-ones. A new approach to methyl L-(2S,4S)-4-methyl-6-oxopipecolate

The sulfoxide-mediated diastereoselective Michael reaction of homochiral α-sulfinylketimines 1a-d and β-substituted ene esters 2a-d (Hua's reaction) was explored. Straightforward cyclization of the open-chain adducts take place under the reaction conditions to provide the 4-substituted 5-(p-tolylsulfinyl)-5,6-dehydropiperidin-2-ones 3 and 7-12, whose stereochemistry is formed in the prior step. Furthermore, the role of the metal ion of the aza-enolate reagents and the steric demands of the O-alkyl ester group have been examined. It seems that the anti-diastereoselectivity depends on metal chelation by the oxygen of the ester as well as the oxygen of the sulfinyl group and the nitrogen in the aza-enolate ((Z)-configuration). In addition, the synthesis of methyl L-(2S,4S)-4-methyl-6-oxopipecolate has been achieved from the suitably functionalized 2-sulfinylketimine 1a (five steps; overall yield: 53-65%).

Sulfoxide-mediated diastereoselective Michael additions. New enantioselective synthesis of C-4 substituted 2-pyroaminoadipic acids

Diastereoselective reactions of suitably functionalized homochiral β-iminosulfoxides with Michael acceptors provide a new and efficient route for the asymmetric synthesis of C-4 substituted 2-pyroaminoadipates. Extension of the scope of the sulfoxide-mediated aza-enolate conjugate addition (Hua's reaction) has also been explored.