1-Substituted 3, 3,7,9-tetramethyl-2-azaspiro[4.5]deca-6,9-dien-8-ones and 3,3,7,9-tetramethyl-2-azaspiro[4.5]deca-1,6,9-trien-8-ones were synthesized by three-component condensation of 2,6-dimethylphenol with isobutyraldehyde and nitriles in concentrated sulfuric acid.Compounds having a 2-azaspiro[4.5]decane skeleton rarely occur in nature. Examples of such structures are annosqualine isolated from the Stems of Annona squamosa [1], spirostaphylotrichins produced by Staphylotrichum coccosporum [2][3][4], triticones (spirocyclic lactams from the fungal plant pathogen Drechslera tritici-repentis [5]), and spiro-arogenate (a spiro-γ-lactam produced by Neurospora crassa from prephenic acid [6,7]). Some 2-azaspiro[4.5]decanes attract certain interest from the viewpoints of medicinal and synthetic organic chemistry. Some synthetic analogs of natural 2-azaspirane derivatives showed high immunosupressive activity [8]. Kazmierski et al. [9] proposed novel HIV-1 protease inhibitors on the basis of a spirocyclic pyrrolidone. It was also found that 2-azaspiranes are formed as intermediate products in the Bischler-Napieralski [10,11] or Ritter [12] syntheses of isoquinolines and phenanthridines. Several synthetic approaches to 2-azaspiro[4.5]-decane derivatives have been reported. Some procedures imply building of 2-azaspiro[4.5]decane skeleton from cyclohexanone or cyclohexene fragments. 2-Azaspiranes can be synthesized according to BuchwaldHartwig via intramolecular cyclization of the corresponding cyclohexanone derivatives [13] and by radical cyclization of N,N-diallyl-2-oxocyclohexanecarboxamides in the presence of Mn(OAc) 3 [14] or of 2-bromo-substituted diene amides, e.g., N-benzyl-2-bromo-N-[1-(cyclohex-1-en-1-yl)vinyl]propanamide, in the presence of CuBr-(C 5 H 5 N) 3 N [15]. A group of methods for the preparation of 2-azaspirane systems is based on dearomatization of arenes with simultaneous construction of pyrrolidinone fragment. Acid-catalyzed intramolecular ipso-cyclization of electron-rich aromatic diazoacetamides [16] or thionium ions generated by reaction of N-benzylglyoxamides with thiols [17] leads to the formation of spirocyclic lactams. 2-Azaspiranes can also be obtained by oxidative radical ipsocyclization of N- [p-methoxy(hydroxy)benzyl]acetamides [18] and substituted N-benzyltrichloroacetamides [19]. developed a procedure for the synthesis of 2-azaspiranes via aromatic nucleophilic substitution in the presence of (η 6 -arene)RuCp + complexes. Another possible way to 2-azaspiranes is based on the reaction of tricarbonyl (η 5 -1-alkyl-4-methoxycyclohexadienylium)iron with difunctional nucleophiles [25]. Intramolecular ene-type [6 + 2]-cyclization of Fe(CO) 3 -(cyclohexa-1,3-diene) complexes having a pendant double bond was reported to afford spirocyclic systems [26][27][28]. 2-Azaspiro[4.5]-deca-6,9-diene-3,8-diones were synthesized by tandem Ugi reaction and intramolecular Michael 5-exoaddition [29].
