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].

Synthesis of 1-Substituted 2-Azaspiro[4.5]deca-6,9-dien-8-ones and 2-Azaspiro[4.5]deca-1,6,9-trien-8-ones by Condensation of 2,6-Dimethylphenol with Isobutyraldehydes and Nitriles. -Three-component condensation of dimethylphenol (I) with isobutyraldehyde (II) and nitriles (III) and (V) in concentrated sulfuric acid gives rise to formation of spiro compounds (IV) and (VI), respectively. To exclude the possibility for ortho attack on the phenol molecule by aldehyde and to suppress side reactions, 2,6-dimethylphenol is used as the aromatic component. -(ROZHKOVA, Y. S.; KHMELEVSKAYA, K. A.; SHKLYAEV, Y. V.; EZHIKOVA, M. A.; KODESS, M. I.; Russ.