Rapid and Multigram Synthesis of Vinylogous Esters under Continuous Flow: An Access to Transetherification and Reverse Reaction of Vinylogous Esters

Abstract

An environmentally benign approach for the synthesis of vinylogous esters from 1,3-diketone and its reverse reaction under continuous-flow has been developed with alcohols in the presence of inexpensive Amberlyst-15 as a catalyst. This methodology is highly selective and general for a range of cyclic 1,3-dicarbonyl compounds which gives a library of linear alkylated and arylated vinylogous esters in good to excellent yield under solvent and metal free condition. Furthermore, the long-time experiment in a continuous-flow up to 40 h afforded 8.0 g of the vinylogous ester with turnover number (TON) = 28.6 and turnover frequency (TOF) = 0.715 h–1 using Amberlyst-15 as a catalyst. Furthermore, a continuous-flow sequential transetherification of vinylogous esters with various alcohols has been achieved in high yield. Reversibly, this vinylogous ester was deprotected or hydrolyzed into ketone using environmentally benign water as a solvent and Amberlyst-15 as a catalyst under continuous-flow process.

A Formal Exchange Reaction between Ketones and Vinyl Ethers with Solid Catalysts

“…Products obtained were characterized by GC–MS and NMR (nuclear magnetic resonance) and compared with previous characterization. 20 Moderate to good yields of vinyl ethers 3a – k and ketones 4a – c were obtained with both catalysts. Diketones 1b , c , g , h are selectively desymmetrized to give the vinyl ethers 3b , c , 3e , 3g , 3h , and 3k , respectively.…”

“…Products obtained were characterized by GC-MS and NMR, and compared with previous characterization. [20] 1, i.e. Amberlyst A16 (20 mol%) and montmorillonite K10 (1 mol%).…”

“…13 C NMR (100 MHz, CDCl 3 ):  = 196.5 (C), 195.6 (C), 171.8 (C), 112.6 (CH), 68.5 (CH 2 ), 52.4 (CH 2 ), 42.0 (CH 2 ), 35.6 (CH 2 ), 30.9 (C), 30.3 (CH 2 ), 29.7 (CH 3 ), 27.9 (CH 3 ), 24.9 (CH 2 ). GC-MS: m/z (%) = 225 (M + ), 225 (10), 196 (20), 182, 168 (71), 154, 140 (16), 71 (100), 57, 43, 29 (27).…”

“…Colors are a guide to the eye by emphasizing same functionalities; the reaction does not transfer the labeled atoms between starting material and product. Products obtained were characterized by GC-MS and NMR, and compared with previous characterization [20].…”

Practical Manufacturing Process for Baloxavir Marboxil: Effective Selection and Replacement of Protective Group toward Enhancement of Crystallization-Induced Diastereomer Transformation

“…23 The synthetic methodology had been wellestablished with regard to 3a 24 starting from 3-benzyloxy-4oxo-4H-pyran-2-carboxylic acid, which was a readily available intermediate employed for the production of dolutegravir sodium. 25,26 With the vinylogous ester from a structural perspective on 3, preliminary investigation proved it promising to work with an addition−elimination sequence by an alkoxide leading to a transesterification protocol for the required displacement of the alkoxy group. 27,28 In particular, 3b was afforded by treatment of 3a with an excess amount of 1-hexanol and sodium tert-pentoxide (NaOt-Am) in tetrahydrofuran (THF) at 0 °C.…”