Other Cyclizations

Synthesis by Other Cyclizations. The epimeric amines (49) have been made by means of a novel S 2 reaction of the corresponding 2-bromo-6-amino-cyclohexanone derivative. Double Michael addition of (+)-a-methylbenzyl-amine to cyclo-octa-2,7-dienone derivatives forms the basis of a synthesis of the enantiomeric forms of adaline (50). Intramolecular Friedel-Crafts alkylation has been used in the synthesis of derivatives of the 2,6-methanobenz-azepine, 2,6-methano-3-benzazocine, 2,6-methano-3-benzazonine, and 

Reactions of Nitrogen-containing Compounds. - Irradiation of cyclic nitrocompounds in base (i.e. as the nitronate anion) leads to ring-expansion [e.g. 

Barluenga, J. Perez-Prieto, and G. Asensio, J. Chem. Soc., Chem. Commun, 1982, 1181. 

The heterolysis of j3-halo-amines (60) has been examined as a function of 

Kresze and W. Dittel, Liebigs Ann. Chem., 1981, 610, and earlier papers in this series. 

Recently, it was reported that imidoylketene imines (97) rearrange at room temperature to form corresponding N-substituted 1,2-dihydropyrimidines 98 via a [l,5]-hydrogen shift167 [Eq. (35)]. 

Takamisawa and co-workers described an unusual cyclization with formation of the ethyl ester of 2-methyl-l,6-dihydropyrimidine-5-carboxylic acid (99), observed by interaction of 2-ethoxymethoxymethyl-3-ethoxypro-pionitrile with acetamidine168 [Eq. (36)]. 

In Poland, Kuran and co-workers demonstrated the formation of dihydropyrimidines by reaction of methyl aluminates with acrylonitriles.169-170 

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A recent report describes the conversion of A-formyl- and N-acetyl-L-leucine into optically active azlactones with dicyclohexyl-carbodiimide (DCC) [Eq. (29)]. Other cyclization reagents, e.g. acetic anhydride, POCI3, SOCI2, and polyphosphoric acid, cause racemiza-tion. These azlactones react with optically active amino acid esters to give esters of dipeptides with retention of activity. 

As in other cyclization reactions, the parent benzo[/]isoindolinediimine as well as substituted derivatives may be employed. 

Note One or more alkyl groups on quinoxaline may become involved in annulation or other cyclization reactions. 

Other cyclizations at phosphorus have been observed when certain phosphinates were used in the acid-catalyzed Mannich reaction. As observed previously with various phosphonous acid derivatives, reaction of aliphatic phosphinic acids with primary amines favored the formation of 2 1 adducts (73). Thus, glycine and other a-amino acids reacted under the typical conditions with excess formaldehyde and alkyl phosphonous acids to give the bis-phosphinylmethyl adducts 125. 

Alternatively, the enamine portion may be located in the Aralkyl chain. For instance, piperidines bearing a 7-chloro substituent yielded quinolizidines 263 through a conjugate addition of the nitrogen atom to acetylenic sulfones followed by an intramolecular alkylation (Scheme 55) <2000JOC4543>. Other cyclizations that are summarized below used as starting materials piperidine derivatives obtained by similar conjugate additions to vinyl sulfones (see Section 12.01.9.3.6). 

Fig. 15 shows that the barrier computed for cyclization of /wzra-cyanophenyl-nitrene (12c) is more than 1 kcal/mol higher than that for either of the other two cyanophenylnitrenes. In addition, the cyclization of 12c is calculated to be more endothermic than any of the other cyclizations shown. Both facts are attributable to the ca. 3 kcal/mol lower energy computed for 12c, relative to both 12a and 12b. 

Asymmetric Diels-Alder and Other Cyclization Reactions... 

ASYMMETRIC DIELS-ALDER AND OTHER CYCLIZATION REACTIONS... 

Other cyclizations to give tetrazolo[l,5-7][l,2,4]triazines published in recent years basically follow the established procedures discussed earlier in CHEC-II(1996) < 1996CHEC-II(8)499> and belong to two categories (1) reaction of 1,5-diaminotetrazole 42 with ct-dioxo reagents, and (2) reaction of a 3-hydrazino[l,2,4]triazine derivative with nitrous acid. 

Sulfur-containing acyclic and cyclic compounds have been prepared from allenyl sulfides in numerous transformations such as substitutions, additions, cydoaddi-tions and other cyclization reactions. Like the other donor-substituted allenes, allenyl sulfides are suitable substrates for regioselective lithiation and substitutions as exemplified in Scheme 8.86 [168, 169,175]. 

As it has been shown, there are many ways to assemble the 1,4-(oxa/thia)-2-azole ring. Most of them are performed by inter- or intramolecular cyclization of suitable acyclic precursors. Some of them are found to be suitable for the synthesis of various ring systems, by using readily available, and properly modified reactants. Of particular importance are the following (a) the cyclizations of sulfenamides leading to (oxa/thia)azolium salts (Scheme 33) (b) the cyclization of hydroxamic acids (Scheme 39) (c) the dipolar cycloaddition methodology (Scheme 40) (d) the cyclizations of chlorosulfenyl chlorides (Scheme 46) and (e) the cyclizations of chloromethane sulfonamides (Schemes 47 and 48). Other cyclizations reported are preparative ways used mainly for the synthesis of specific compounds and the scope of these reactions has not been widely studied. 

Several workers have studied other cyclization reactions involving various leaving groups. Thus, compounds 138 have been shown to cyclize to 1,3-thiazines (139) under acidic or alkaline conditions. The earliest recorded reaction of this type is that of Kahan,273 who in 1897... 

HydroxycarbazoIes react with citral to form either pyrano[3,2-a]carbazoles (132) or pyrano[2,3]carbazoles (133), whilst 1-hydroxycarbazoles produce pyrano[2,3-a]-carbazoles (81SC823, 81H(16)1445). Other cyclization reactions involving substituted pyrroles or indoles and aldehydes or ketones in which the substituent becomes part of the new ring system are discussed under the relevant sections relating to the reactivity of the substituent. 

Cyclization of allylic alcohols to form epoxides has been particularly problematical, and the reactions have been more of mechanistic than of synthetic interest. For reactions conducted under basic conditions, it is possible that epoxide formation involves initial halogen addition followed by nucleophilic displacement to form the epoxide. Early examples of direct formation of epoxides from allylic alcohols with sodium hypobromite," bromine and 1.5 M NaOH,12 and r-butyl hypochlorite13 have been reviewed previously.fr Recently it has been shown that allylic alcohols can be cyclized effectively with bis(jym-collidine)iodine(I) perchlorate (equation 3).14 An unusual example of epoxide formation competing with other cyclization types is shown in equation (4).15 In this case, an allylic benzyl ether competes effectively with a -/-hydroxyl group as the nucleophile. 

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