2,3,4,9-Tetrahydro-9-(3-hydroxy-1,4-dioxo-1H-dihydro-naphthalen-2-yl)-8-methoxy-3,3-dimethyl-1H-xanthen-1-one

Abstract

Abstract:The title compound 2,3,4,9-tetrahydro-9-(3-hydroxy-1,4-dioxo-1H-dihydronaphthalen-2-yl)-8-methoxy-3,3-dimethyl-1H-xanthen-1-one (5) was obtained by the nucleophilic addition of 2-hydroxy-1,4-naphthoquinone (4) to 2H-chromene derivative 3, which was prepared by the domino three-component coupling reaction of aryne precursor 1 with DMF and the active methylene compound dimedone (2). The one-pot synthesis of the title compound 5 from aryne precursor 1 was also achieved.Keywords: multi-component reaction; domino reaction; arynes; heterocycles; synthesis Arynes are highly reactive and kinetically unstable intermediates for constructing multisubstituted arenes with structural diversity and complexity [1,2]. In particular, the recent aryne-based chemistry has made great advances in synthetic chemistry [3][4][5][6][7][8][9][10][11][12][13][14]. Our laboratory is interested in developing domino reactions using arynes. We have recently developed the efficient insertion of arynes, generated in situ from ortho-(trimethylsilyl)aryl triflates and the fluoride ion, into the C=O π-bond of DMF [15][16][17][18][19][20].Synthetic strategies involving domino processes offer the advantage of multiple carbon-carbon and/or carbon-heteroatom bond formations in a single operation [21,22]. In this paper, we report two synthetic methods for preparing the title compound 5 via a domino multicomponent coupling reaction starting from the generation of an aryne. Moreover, this molecule 5 has a pharmaceutically important structure, because a similar type of compound was studied as a neuropeptide Y Y5 receptor antagonist by Merck-Banyu researchers [23]. OPEN ACCESS

Recent Uses of N,N-Dimethylformamide and N,N-Dimethylacetamide as Reagents

“…Arynes, which are easily obtained from, for example 2-(trimethylsilyl)phenyl trifluoromethane-sulfonate, undergone a [2 + 2] cyclization with DM giving a benzoxetene and its isomer, the ortho -quinone methide ( Scheme 3 ). Trapping of these intermediates provides various products, which contain the formyl or acetyl CH part and the O atom of DM (Equations (86) [ 19 ], (87) [ 20 ], (88) [ 21 ] and (89) [ 97 ]), or the HCNMe 2 and O fragments of DMF (see Section 18 ).…”

“…When uncertainty is expressed by the authors or suspected by us, the atom is typed in italic. Mechanistic schemes are not reported, but Scheme 2 [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ] summarizes different proposed reactions of DM with the corresponding literature references, where DM acts as either a nucleophilic or electrophilic reagent, or leads to neutral, ionic or radical species. The review is divided in Sections depending on the DM fragment(s) which is (are) incorporated into the reaction product.…”

Transition-Metal-Free Activation of Amide Bond by Arynes

“…The trapping reactions of transient intermediates generated from arynes precursors and DMF with a variety of reactants have been widely studied as being synthetic approaches to oxygen atom-containing heterocycles [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. The synthesis of 2 H -coumarin derivatives was also studied [ 34 , 35 , 36 ].…”

“…Additionally, the trapping reaction of transient intermediates was successfully applied to a four-component coupling reaction for the convenient synthesis of xanthene derivatives [ 34 , 41 , 42 ].…”

Synthesis of Oxygen Heterocycles via Aromatic C-O Bond Formation Using Arynes

“…Four-component coupling reaction using two different 1,3-diketones also proceeded by a one-pot procedure. When 2-hydroxy-1,4-naphthoquinone 46 was used as a nucleophilic reactant, the direct one-pot synthesis of xanthene derivative 47 from precursor 22 was achieved [61]. These transformations involve the three C-C and two C-O bond-forming processes under mild neutral conditions.…”