Cyclization, also

Category Ic cyclizations involve formation of the C3-C3a bond and require aniline derivatives with a nitrogen substituent appropriate for such reaction. Some, but not all, such cyclizations also require an o-substituent, frequently halogen. The rctrosynthetic transformations corresponding to the most important of this group of syntheses are shown in Scheme 4.1... 

This cyclization also gives good results in the case of derivatives of naphthalene, anthracene, phenanthrene, and other aromatic substrates [76]... 

When bromoacetyl chloride is used instead of bromoacetic acid, the anilide 33 is formed at the first stage. Its subsequent cyclization also leads to 32. This approach to benzotellurazinone is similar to that developed for the synthesis of 2//-l,4-benzothiazin-3(4//)-ones (66CJC1247). Significantly, attempts to isolate the intermediate sulfonium salts analogous to 30 were unsuccessful. 

Some cyclization also occurs with the bromide, but not with the chloride or the tosylate. The secondary iodide, 6-iodo-l-heptene, gives a mixture of cyclic and acyclic product in THF.165... 

The cyclization of y -hydroxy ketones is useful for the formation of pyrans,306,403 both directly and via rearrangement, as illustrated in Eq. 231.153 As with their acyclic counterparts, these cyclizations also occur with the silyl ethers of the hydroxy ketones where Et3SiH/BiBr3 is used with the TBS and TES ethers.342,404 A methyl thiomethyl ether is also capable of undergoing the reductive cyclization 405 In like manner, 1,4-diols and e-hydroxy ketones provide oxepanes, with I ds Si H or PhMe2SiH/TMSOTf being especially effective (Eqs. 232 and 233).336,406 The trimethylsilyl ether of the alcohol also provides the oxepane.306... 

Hegedus synthesis of ( )-clavicipitic acid //-acetyl methyl ester culminated in the Pd-induced cyclization of 238 to 239, the latter of which was reduced to the target mixture [251], Substrate 238 was prepared via a Heck reaction with the corresponding 4-bromo compound 223 and 2-methyl-3-buten-2-ol (83%). The cyclization also occurs with tosic acid (97%). 

Enynes undergo a similar cyclization to alkylidene thioethers on reaction with thiophenol in the presence of AIBN. This cyclization also involves a vinyl radical (equation I).8... 

Compounds with the structure 116 carrying ethoxy or methoxy groups in D-position are prepared from o-alkoxyanilines. Not only are cyclization and condensation achieved at comparatively lower temperature, between 170 and 175°C, but the reaction also proceeds at a higher rate than for compounds with D =H. One of the above-mentioned condensation agents is similarly necessary in this case. o-Dichlorobenzene, for instance, is a suitable organic solvent. The list of solvents for condensation and cyclization also includes trichlorobenzene and nitrobenzene. The reaction conditions are not markedly affected by the type of substitution in positions A and B. 

Investigations have also examined the photochemical outcome of the inclusion of other aromatic substituents onto the norbornadienes. Examples of this are the direct and sensitized irradiation of the naphthyl-substituted derivatives 249 that brings about cyclization to 250. Sensitization of the cyclization with ketones such as benzophenone leads to a much cleaner reaction. Biacetyl has also been used as the sensitizer130,131. Cyclization also occurs with the norbornadiene 251132. 

Cathodic cyclizations also involve various reactive intermediates. 

Cyclization also accompanies the hydroformylation of unsaturated C4-alcohols catalyzed by a rhodium/PNS (27) complex (Scheme 4.14). Interestingly, an approximately 3-fold increase was observed in the activity of the catalyst upon increasing the pH from 7 to 9.5 [95]. Rhodium could be efficiently recycled in the aqueous phase, but since there was a considerable pH-drop during the reaction (from 9 to 5) the activity of the catalyst had to be regenerated by addition of a base (NaOH). 

Combination of MCR with the Pictet-Spengler cyclization also leads to different types of scaffolds with ketopiperazine fused ring systems. Tetrahydro-jS-carboline scaffold 221 was prepared in a convergent, two-step procedure [67]. An array of indole derivatives was prepared by the reaction of tryptophan derivative 222, aldehyde 223, carboxylic acid 224, and bifunctional amine 214 (Scheme 40). 

Hydrocarbon bond saturation and cyclization also play roles in water solubility. Figure 6.7 shows that, among the six-carbon hydrocarbons, the various forms of hexane, C6H14, have the lowest solubility, and the hexenes and cyclohexane with the formula C6H12 have three times the solubility. Fewer hydrogen atoms consistently lead to higher solubilities, and benzene has one hundred times the water solubility of normal and iso-hexanes. 

While enantioselective transition metal catalysis continues to be important, several useful all-organic catalysts have been developed over the past few years. Tomislav Rovis of Colorado Stale University has reported (J. Am. Chem. Soc. 2004, /26, 8876) that the triazolium salt 5 catalyzes the enantioselective Stetter-type cyclization of 4 to 6. The cyclization also works well for the enantioselective construction of azacyclic, thiacyclic and carbocyclic rings. 

Figure 7. By increasing the number of rungs and the size of a molecular ladder, the probability of further twisting of the strip before cyclization also increases [40],...

This cyclization also effects a synthesis of helminthogermacrene (5) and p-elemene (6) from 4.2... 

Another version of the reaction of 2-aminopyridines and /i-oxo esters is the isolation and cyclization of the intermediates of type 38 or 39. Compounds of type 38 were cyclized in concentrated sulfuric acid at ambient37 or elevated temperature,34,36 38,43,52,53 in polyphosphoric acid,41 or in toluene in the presence of p-toluenesulfonic acid.48 Cyclization of the acrylates (39) was carried out by heating without solvent47 or in solution in water,39-40 diethylbenzene,47 or toluene in the presence of p-toluenesulfonic acid.48 Cyclization also took place when 39 was chromatographed on a silica gel column.48... 

This cyclization also is useful in an efficient route to the ring system 5 of the natural product aphidicolin (6).3... 

Diphenyl-l-propanone (19) is found to give the cyclization product 22 in good yield when the reaction is carried out in superacid.19 This acid-catalyzed cyclization also shows a dramatic dependence on the acidity of the reaction medium a yield of 72% in 100% CF3SO3H (Ho —14.1) a yield of 7% in 6% w/w CF3SO3H 94% CF3C02H (H0 -8.7) a yield... 

Stannic Chloride pn the Free Acid. Ring closure by heating the free acid with stannic chloride at 100-120° has been shown to be successful on several types of acids.85 47> 8 88 80, 189 819 These and some other acids which have been cyclized by this method may be found in Table XI. In four instances (items 3, 7, 14, 17) stannic chloride treatment gave better results than sulfuric acid. Eleven of the acids in Table XI (items 3, 5, 8, 9, 10,12, 13, 14, 16, 17, 18) have been cyclized also by the Friedel-Crafts method on the acid chloride. With seven acids (3, 6, 8, 9, 12, 14, 17) the yields were better, while with four (5, 10, 16, 18) they were lower, than with stannic chloride. Except for one (18) of these latter acids, however, there seems to be some question as to whether the optimum conditions for the Friedel-Crafts reaction were employed. Of the acids (4, 6,12) which have since been cyclized with hydrogen fluoride, considerable improvement in yields was realized. 

---