Malaysian Journal of Analytical Sciences Vol 26 No 2 (2022): 269 - 282

 

 

 

 

DIASTEREOSELECTIVE REDUCTION OF ENDOCYCLIC β-ENAMINO ESTER: AN APPROACH TO PREPARE DIASTEREOPURE MULTISUBSTITUTED PYRROLIDINE β-AMINO ESTERS

 

(Penurunan Diastereoselektif Terhadap Ester β-Enamino: Sebuah Pendekatan untuk Menyediakan  Ester β-Amino Pirolidin Multi-Terganti Diastereotulen)

 

Ayisy Amirul Afti¹*, Zurina Shaameri², Ahmad Sazali Hamzah², Nor Saliyana Jumali¹

 

¹Department of Chemistry,

Kulliyyah of Science, International Islamic University Malaysia, 25200 Kuantan, Pahang, Malaysia.

²Organic Synthesis Research Laboratory,

Institute of Science,

Universiti Teknologi MARA, 42300 Bandar Puncak Alam, Selangor, Malaysia.

 

*Corresponding author:   ayisypale@gmail.com

 

 

Received: 26 November 2021; Accepted:  27 February 2022; Published:  28 April 2022

 

 

Abstract

A set of chiral multisubstituted pyrrolidine diastereomers containing β-amino ester moiety 5a-c were successfully synthesized from  4-carbethoxy-2,3-dioxo-5-phenylpyrrolidine 1. The key intermediate endocyclic β-enamino ester 4 were prepared by methylamination of the precursor 1. Afterwards, acid-catalyzed reduction of 4 using sodium cyanoborohydride afforded target products 5 with moderate diastereoselectivity. Other procedures to reduce 4 including the use of sodium triacetoxyborohydride in acetic acid and catalytic hydrogenations are compared with the aforementioned approach in terms of selectivity. We hereby describe several plausible  reaction mechanisms from the outcome of this experiment.

 

Keywords:     pyrrolidine, β-enamino ester, diastereoselective reduction, patalytic hydrogenation, sodium cyanoborohydride

 

Abstrak

Satu set diastereomer pirolidin multi-terganti kiral yang mengandungi bahagian ester β-amino 5a-c telah berjaya disintesis dari  4-karbetoksi-2,3-diokso-5-fenilpirolidin 1. Perantara utama, ester β-enamino endosiklik 4, telah disediakan melalui metilaminasi pendahulu 1. Kemudian, penurunan 4 yang dimangkinkan oleh asid menggunakan natrium sianoborohidrid menghasilkan produk sasaran 5 dengan diastereoselektiviti yang sederhana. Tatacara lain untuk  menurunkan 4 termasuk penggunaan natrium triasetoksiborohidrid dalam asid asetik dan penghidrogenan mangkin telah dibandingkan dengan kaedah terdahulu dari sudut selektiviti. Di sini, kami menghuraikan beberapa mekanisme tindakbalas yang munasabah daripada hasil eksperimen ini.

 

Kata kunci:       pirolidin, ester β-enamino, penurunan diastereoselektif, penghidrogenan mangkin, natrium sianoborohidrid

 

 

 

Graphical Abstract

 

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