Diels-Alder cyclo addition reactions of 1,1-dichloro-2,3,4,5-tetraethylgermole and 1-chloro-2,3,4,5-tetraethylphosphole with maleic acid anhydride and maleimide

Abstract

The Diels-Alder reaction of 1-chloro-2,3,4,5-tetraethylphosphole with maleic anhydride and with maleimide yields 4-chloro-1,7,8,9-tetraethyl-4-oxa-10-phosphatricyclo[5.2.1.0 2,6 ]deca-8-ene-3,5-dione (1) and 4-chloro-1,7,8,9-tetraethyl-4-aza-10-phosphatricyclo[5.2.1.0 2,6 ]deca-8-ene-3,5-dione (2). The molecular structure of 1 confirms the formation of the endo-cyclo-adduct with the chlorine atom in an anti-position to the C=C double bond. In contrast to this chlorophosphole, 1,1-dichloro-2,3,4,5-tetraethylgermole reacts with two equivalents of the maleic derivatives to 1,4,7,8-tetraethylbicyclo[2.2.2]oct-7-ene-2,3,5,6-tetracarboxylic acid anhydride (3) as well as the aza-analogue 4. The molecular structure of 3 shows the formation of an exo,exo-product. The 1,1-dichloro-2,5-bis(trimethylsilyl)-3,4-diorganylgermoles with R = Me (5), nPr (6) and Ph (7) show no reactivity toward maleic acid derivatives.

Design, Synthesis and Evaluation of Fused Bicyclo[2.2.2]octene as a Potential Core Scaffold for the Non-Covalent Inhibitors of SARS-CoV-2 3CLpro Main Protease

“…Variously substituted bicyclo[2.2.2]octenes were thus prepared from corresponding 2 H -pyran-2-one derivatives and maleic anhydride [ 32 , 33 , 34 , 35 , 38 ]. There are also some alternative synthetic strategies towards bicyclo[2.2.2]octenes, such as reactions of maleic anhydride with thiophene-1,1-dioxide (with the elimination of SO 2 ) [ 39 , 40 ] or with a germanium analogue [ 41 ]. Other pathways include reactions of maleic anhydride with substituted 3a,7a-dihydro-1,3-isobenzofurandione [ 42 ], with 4-hydroxy-3,4-diphenylcyclopent-2-en-1-one [ 43 ], with ( E )-(4-bromopenta-2,4-dien-2-yl)benzene [ 44 ], or with 2,4-dimethylcrotonaldehyde [ 45 ].…”