Synlett 2021; 32(07): 713-717
DOI: 10.1055/a-1326-6973
letter

Ynoate-Initiated Selective C–N Esterification of Tertiary Amines under Transition-Metal and Oxidant-Free Conditions

Feixiang Sun
a   College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai 201620, P. R. of China
,
Huangdi Feng
a   College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai 201620, P. R. of China
c   Shanghai Engineering Research Center of Textile Chemistry and Cleaner Production, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai 201620, P. R. of China
,
Liliang Huang
a   College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai 201620, P. R. of China
,
Junhai Huang
a   College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai 201620, P. R. of China
b   State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, 201203, P. R. of China
› Author Affiliations
We gratefully acknowledge the financial support from the National Natural Science Foundation of China (22078192, 31702070), the Natural Science Foundation of Shanghai (19ZR1437900), and Shanghai University of Engineering Science (E3-0903-19-01366).


Abstract

An efficient and selective method for metal- and oxidant-free deaminated esterification of tertiary amines is presented. In this protocol, ynoates play a key role to activate the Csp3–N bond through a process of in situ generation of zwitterionic salts. The transformations show that Csp3–N bond in the zwitterionic species has a lower dissociation energy than Csp2–N bond, leading to break preferentially and be trapped by carboxylic acids to generate the corresponding products in moderate to good yield.

Supporting Information



Publication History

Received: 24 October 2020

Accepted after revision: 01 December 2020

Accepted Manuscript online:
01 December 2020

Article published online:
05 January 2021

© 2020. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
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  • 17 General Procedure for the Synthesis of Dibenzyl 2,6-Pyridine-dicarboxylate (4aa) A mixture of pyridine-2,6-dicarboxylic acid (2a, 83.5 mg, 0.5 mmol, 1.0 equiv) and ethyl propiolate (3a, 157 mg, 1.6 mmol, 3.2 equiv) was added a 10 mL tube along with a magnetic stir bar, and then 2 mL 1,4-dioxane was added. The tube was stirred and refluxed in oil bath at 80 °C. Subsequently, N,N-dimethylbenzylamine (1a, 202 mg, 1.5 mmol, 3 equiv) solved in 1 mL 1,4-dioxane was added to the tube slowly for 10 min. And the tube was stirred again and refluxed at 80 °C for 12 h. After the removal of the volatiles in vacuo, the crude residue was loaded on a silica gel (100–200 mesh) column and flashed with 20% ethyl acetate in petroleum ether to afford the desired product 4aa in 81% yield. Dibenzyl 2,6-Pyridine-dicarboxylate (4aa) White solid; 140 mg, 81% yield; mp 111–113 ℃. 1H NMR (400 MHz, CDCl3): δ = 8.27 (d, J = 7.8 Hz, 2 H), 7.97 (t, J = 7.8 Hz, 1 H), 7.48 (m, J = 7.7 Hz, 4 H), 7.42–7.31 (m, 6 H), 5.45 (s, 4 H). 13C NMR (101 MHz, CDCl3): δ = 163.90, 148.01, 137.79, 134.97, 128.27, 127.88, 127.58, 67.26. Dibenzyl 2,6-Furan-dicarboxylate (4ab) White solid; 144 mg, 86% yield; mp 73–75 ℃. 1H NMR (400 MHz, CDCl3): δ = 7.45–7.33 (m, 10 H), 7.20 (d, J = 4.1 Hz, 2 H), 5.36 (s, 4 H). 13C NMR (101 MHz, CDCl3): δ = 157.39, 146.36, 134.75, 128.30, 127.97, 118.22, 66.66. Dibenzyl 2,6-Thiophene-dicarboxylate (4ac) White solid; 101 mg, 57% yield; mp 56–58 ℃. 1H NMR (400 MHz, CDCl3): δ = 7.76 (s, 2 H), 7.46–7.33 (m, 10 H), 5.35 (s, 4 H). 13C NMR (101 MHz, CDCl3): δ = 161.38, 139.01, 135.35, 133.25, 128.60, 128.28, 67.30. HRMS (EI): m/z calcd for C20H16O4S [M]+: 352.0764; found: 352.0765.