A Convenient Allenoate-Based Synthesis of 2-Quinolin-2-yl Malonates and β-Ketoesters

Abstract

N-Protected o-aminobenzaldehydes smoothly react with α,γ-dialkylallenoates under Brønsted basic conditions to yield 2,3-disubstituted quinolines. This three-step reaction cascade of Michael addition, aldol condensation, and 1,3-N → C rearrangement uses the complete protecting group as a building block in a highly efficient C,C-bond formation of a new all-carbon quaternary center. Carbamate protected substrates (N-Boc, N-Cbz, N-Alloc) thus give 2-quinolin-2-yl-malonates, while amide protected substrates (N-Ac, N-Bz) afford 2-quinolin-2-yl-β-ketoesters in high yields.

Recent Advances in Metal-Free Quinoline Synthesis

“…This creates the active intermediates, which undergo crossed aldol addition and then cyclize with loss of H2O to give the final quinoline products 49 in good to excellent yield. Citing the inherent electrophilic and nucleophilic character of allenoates (α-allenic esters), Selig and Raven [38] investigated the use of these compounds in the formation of quinolines. Although their initial trials using o-aminobenzaldehyde did not result in the cyclization product, they found that monoprotection of the amine allowed the process to occur.…”

“…Interestingly, they observed formation of both the desired quinoline product as well as a second product that featured a migration of the protecting group and formation of a new quaternary center (Figure 23). They propose the mechanism to operate through an aza-Michael addition of the Brønsted base-promoted amide anion of the Citing the inherent electrophilic and nucleophilic character of allenoates (α-allenic esters), Selig and Raven [38] investigated the use of these compounds in the formation of quinolines. Although their initial trials using o-aminobenzaldehyde did not result in the cyclization product, they found that monoprotection of the amine allowed the process to occur.…”

Metal-free domino one-pot protocols for quinoline synthesis

“…This transformation involves a three-step reaction cascade of Michael addition, aldol condensation, and 1,3-N / C rearrangement (Scheme 41). 105 The treatment of 3-(2-bromophenyl)-3-oxopropanals 115 with amines 1 in presence of K 2 CO 3 in dimethylsulfoxide led to formation of 3-substituted 4-quinolones 114. 106 Reaction cascade involves base promoted enamine Iimine II transformation followed by dehydrobromination leading to cyclization to yield quinolone 114 (Scheme 42).…”

Asymmetric [4 + 2] cycloaddition synthesis of 4H-chromene derivatives facilitated by group-assisted-purification (GAP) chemistry

“…[25][26][27][28][29][30][31][32][33] In addition, it has been reported that allenes can react with nucleophilic compounds in the presence of carbonate catalysis (Scheme 1). [34][35][36] Shi and co-workers utilized allene esters and ketones to establish the rst synthesis of chromenes via [4 + 2] cycloaddition assisted by nitrogen-based catalysts such as DABCO and DBU (Scheme 2a). [37][38][39] In 2015, Tong and co-workers reported the synthesis of 4H-chromenes from d-acetoxy allenoates with salicylaldehyde derivatives in an amine-catalyzed reaction (Scheme 2b).…”

“…12,34,36,54 especially the recent review regarding stepwise[4 + 2] cycloaddition reactions, 55 a plausible mechanism for the reaction is represented in Scheme 5. The sequence is initiated by deprotonation of salicyl N-phosphonyl imine 1 by cesium carbonate as a non-nucleophilic base to form intermediate A.…”