Cyclization behavior

In later studies by various groups, the enyneallene motif was incorporated into more complex hydrocarbon structures, allowing not only a better understanding of the Myers cyclization but also the generation of polycyclic hydrocarbons, some of them resembling the steroid core unit. Conceptually, these latter cyclizations are reminiscent of Johnson s biomimetic cyclization reactions with the main difference that here radical intermediates are involved rather than carbocations. Typical starting materials in these studies are the allenes 221 [87], 222 [88] and 223 [89], their cyclization behavior being discussed in Chapter 20. 

The same cyclization behavior of the p-polycarbonyl chain—not to fold in the middle, as postulated for the alkaloid biosynthesis (see Scheme 3), but to roll up from an unprotected end—was also observed for the parent compound, the free 3-pentaketone 30, itself, which led in vitro directly to doubly cyclized products like 49 (52). This type of chemical cyclization is sometimes used by nature, as well, and thus could be exploited biomimetically (50,51,53) for a first total synthesis of the aloenin aglycon (52), a natural product from Aloe ar-borescens var. natalensis, in which the carbon chain is similarly folded. The same type of cyclization, using the (3-polycarbonyl chain in its complete, non-decarboxylated form 55, could achieve a still shorter synthesis of 52 (Scheme 9), being even more closely oriented to the biosynthesis (50,51). 

Scheme 9. Synthesis and cyclization behavior of the polycarbonyl acid 55 (50,5/),...

The precursors 127 and 128 were both obtained with well-established methods, but they differed completely in their cyclization behavior. 

D. Rigby, H. Sun and B. E. Eichinger. Computer simulations of poly(ethylene oxide) Force held PVT diagram and cyclization behavior. Polym. Int. 44, 1997, 311. 

Large ring heterocyclic radicals are not particularly well known as a class. Their behavior often resembles that of their alicyclic counterparts, except for transannular reactions, such as the intramolecular cyclization of 1-azacyclononan-l-yl (Scheme 1) (72CJCH67). As is the case with alicyclic ethers, oxepane in the reaction with r-butoxy radical suffers abstraction of a hydrogen atom from the 2-position in the first reaction step (Scheme 2) (76TL439). 

The intramolecular cyclization of 2-alkynylaryldiazonium salts (Richter reaction) leads not only to 4-hydroxy- but also to 4-bromo- and 4-chlorocinnolines. The behavior of alkynylpyrazolediazonium chlorides differs from that of their benzene analogs. The Richter reaction of the series of alkynylaminopyrazoles gives only 4-halo derivatives of l//-pyrazolo[3,4-c]pyridazines and l//-pyrazolo[4,3-c] pyridazines, and mainly hydroxy derivatives of 2//-pyrazolo[3,4-c]pyridazines. 

The smooth intramolecular nucleophilic displacement of biphenyl carboxylic acids leading to benzocoumarins (See Section II.A.) inspired also investigation of the behavior of similar diphenyl ether, diphenyl sulfide and A-methyldiphenyl amine derivatives 458 under similar conditions. However, all these attempts to achieve cyclization to tricyclic compounds 459 were unsuccessful, probably due to the unfavorable stereochemistry for the formation of the required seven-mem-bered transition states and also to the presence of the deactivating bridge groups X (Eq. 42) [68JCS(C)1030]. 

Naphtho[2,l-6]furo[2,3-c][l,2,4]triazines 198 were prepared (88JHC-1117) by the reaction of 4-5-benzocoumaran-2,3-dione with thiosemicar-bazide to give 195, whose ethylation in the presence of sodium hydroxide gave 197 via 196. Reaction of 197 with aniline gave 198 via the first displacement of the ethylthio group whose product could be isolated with a shorter reaction time. On the other hand, the similar sequence of reactions on coumaran-2,3-diones differs markedly from that of 4,5-benzocoumaran-2,3-diones, where the cyclization of 195 to 198 could not be effected. The behavior of the later dione resembles that of isatin and thianaphthenequinone (Scheme 41). 

Many anodic oxidations involve an ECE pathway. For example, the neurotransmitter epinephrine can be oxidized to its quinone, which proceeds via cyclization to leukoadrenochrome. The latter can rapidly undergo electron transfer to form adrenochrome (5). The electrochemical oxidation of aniline is another classical example of an ECE pathway (6). The cation radical thus formed rapidly undergoes a dimerization reaction to yield an easily oxidized p-aminodiphenylamine product. Another example (of industrial relevance) is the reductive coupling of activated olefins to yield a radical anion, which reacts with the parent olefin to give a reducible dimer (7). If the chemical step is very fast (in comparison to the electron-transfer process), the system will behave as an EE mechanism (of two successive charge-transfer steps). Table 2-1 summarizes common electrochemical mechanisms involving coupled chemical reactions. Powerful cyclic voltammetric computational simulators, exploring the behavior of virtually any user-specific mechanism, have... 

Some Bis reactions may lead to intramolecular cycles that will not affect the elasticity behavior of the gel, and pendant, unreacted, gronps may form where only the crosslinker reacts at one of its double bonds [315]. Tobita and Hamielec [393] found that primary cyclization, i.e., the formation of loop cycles, may consnme as much as 80% of... 

Sometimes acylium ions lose carbon monoxide to generate an ordinary carbonium ion. It will be recalled that free acyl radicals exhibit similar behavior at high temperatures. Whether or not the loss of carbon monoxide takes place seems to depend on the stability of the resulting carbonium ion and on the speed with which the acylium ion is removed by competing reactions. Thus no decarbonylation is observed in Friedel-Crafts reactions of benzoyl chloride, the phenyl cation being rather unstable. But attempts to make pivaloyl benzene by the Friedel-Crafts reaction produce tert-butyl benzene instead. With compound XLIV cyclization competes with decarbonylation, but this competition is not successful in the case of compound XLV in which the ring is deactivated.263... 

Zn2+-catalyzed cleavage of (Zn2+ HPNPP)2 in ethanol discussed above.85 For the slower reacting MNPP, the chemical cleavage step (represented by k3 and requiring a methoxide which is probably coordinated to one or both of the metal ions in 35 2Zn(II)) is relatively slow, so that both the pre-equilibrium steps are established and typical Michaelis-Menten behavior is observed with saturation at higher [35 2Zn(II)]. On the other hand, with the far more reactive HPNPP the chemical cyclization step, /c3, is proposed to be faster than the k 2 step in the concentration range of 35 2Zn(II) used here. In this event, the observed kinetics would be linear in [35 2Zn(II)] as is the case in Fig. 20, with kohs — /c, [35 2Zn(I )]k2/(k, + k2). 

Cyclic analogs of DMT and DET, i.e, 43 and 44, respectively, have been synthesized the aziridine 43 appears to possess activity as a CNS depressant (171), while the pyrrolidine 44 displays some behavioral activity. Compound 44 was active in Hall s open-field test but was less active than DET (38) (23). In attempts to measure hyperthermic activity, 44 was found to be rather toxic in rabbits (111). Oddly enough, no cyclic analog has ever shown activity/potency comparable to its acyclic counterpart. Thus, based only on scant animal data, cyclization of the lower dialkyl homologs apparently does not lead to marked behavioral activity. 

Hydrocarbon 136 subsequently cyclizes to a bismethylencyclobutene again, 137, in which the triple bonds of the substituent are so close that they can engage in a [2+ 2] cycloaddition, leading to the doubly annelated hydrocarbon 138. For less highly unsaturated bisallenes, a similar behavior is observed and they allowed the determination of the stereochemistry of the first ring-closure step [51]. 

Many hydrocarbon derivatives of 22 have since been prepared [81, 82] they are mostly of interest because of their thermal cyclization reactions (see below) [8, 83, 84], although their behavior in cycloaddition reactions could also lead to new preparative insights [79]. 

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