Synthesis of 6H‐1,2‐oxazines by hetero Diels‐Alder reactions of nitroso alkenes towards methoxyallenes

Abstract

Regioselective hetero Diels-Alder reactions of in-situ generated nitroso alkenes 2-4 with methoxyallene derivatives 1 provide 4H-1,2-oxazines 5-7 with an exo-methylene group at C-5. These primary cycloadducts are smoothly transformed into conjugated GH-1,2-oxazines 11 -13 by base or acid catalysis. The bicylic nitroso alkene 17 and methoxyallene (1 a) combine to give the tricyclic 1,2-oxazine 18, thus demonstrating that an exo-transition state is favoured in this [4+2] cycloaddition. The reaction of the sterically hindered methoxyallene 1 h with nitrosostyrene affords the cycloadduct 22 in low yield. 22 is very likely formed by a two-step Diels-Alder reaction via a zwitterion. Allene derivatives lacking a methoxy group are not sufficiently reactive towards nitroso alkenes and do not provide 1,2-oxazines.5,6-Dihydro-4H-1,2-oxazines A are heterocycles with a promising though not completely explored synthetic potential*). Their efficient preparation from alkyl or silyl enol ethers by hetero Diels-Alder reactions of in-situ generated nitroso alkenes B has been reported3). In this paper we describe the cycloadditions of B to easily available methoxyallene derivatives4) making 6H-1,2-oxazines C 5,6) accessible. The CC-double bond in C is a welcome tool which allows further functionalization of these heterocycles -e. g. by addition reactions -and should thus considerably raise the possibilities to use 1,Zoxazines as intermediates in the stereoselective synthesis of polyfunctionalized compounds.

Design of a Mesoscale Continuous‐Flow Route toward Lithiated Methoxyallene

“…The obtained 2‐methoxy‐1,1‐diphenyl‐2,3‐butadien‐1‐ol 6 is a known compound. Spectroscopic data were in agreement with reported data . More experimental details, spectroscopic data, procedures, and the results of all optimization experiments can be found in the Supporting information.…”

A Modular Synthesis of Functionalized Pyridines through Lewis‐Acid‐Mediated and Microwave‐Assisted Cycloadditions between Azapyrylium Intermediates and Alkynes

“…Melting points were measured with a Reichert apparatus (Thermovar) and are uncorrected. The 1,2‐oxazines 1a ,8c 1b ,8b 4 ,8b 5 ,8c 7a and 7b ,17 and 12 17 and the alkynes 2i , 2j ,21 2k ,22 2f ,12 2g ,23 and 18 24 were prepared according to literature procedures.…”

Conjugated nitrosoalkenes

“…For methoxyallene, the steric obstacles to the exo-approach prove to be insignificant, and consequently, this alkene, like trimethylsilyloxyethylene, forms predominantly the exo-adduct (the exo : endo ratio is 92 : 8). 131 The fact that the reaction of 1-nitroso-3,4-dihydronaphthalene 88 with allyltrimethylsilane is less diastereoselective than its reaction with trimethylsilyloxyethylene has been explained 128 by different reactive conformations of these molecules. Intramolecular [4+2]-cycloaddition of the nitroso-alkene fragment to the vinyl-ether fragment in compound 90 has been studied.…”

“…8,14,18,120,129 Another type of nucleophilic dienes, methoxyallenes 83, readily react with nitrosoalkenes to give 6-methoxy-substituted cycloadducts 84 with high regioselectivity. 130,131 The successful synthesis of these compounds opened up new opportunities for using the oxazine ring in various transformations. 132 ± 136 Unfortunately, the attempt to extend cycloaddition to allene, phenylallene, and trimethylsilylallene was unsuccessful, indicating that the electronic requirements to allenes are stricter than those to alkenes.…”