Cyclization of esters

Zhang68 has applied the cyclization of esters to the formation of a-methylene-y-butyrolactones, thus offering a novel and enantioselective entry to these substructures. The importance of this unsaturated lactone is evidenced by its ubiquitous presence in nearly a third of all naturally occurring secondary metabolites. The Alder-ene reaction has been applied to a formal total synthesis of (+)-pilocarpine, a leading therapeutic reagent for the treatment of narrow and wide glaucoma. Zhang intersected Btichi s synthetic intermediate (i )-181 (Scheme 47) in only two steps with a 99% ee and a 91% overall yield. In comparison, Biichi synthesized (i )-181 in five steps with a 92% ee and a 20% overall yield. 

Tab. 16.2 Influence of the ligand bound to rhodium on the diastereoselectivity of the cyclization of ester 27...

Dihydro-4H-benzo[/]pyrrolo[l,2-fl][l,4]diazepin-4-one 220 is a product of reductive cyclizations of ester nitrile 219a (R = COOMe, = CN), while amido... 

Similarly, the facile cyclization of esters 7 and 10 was observed57 58. Again, a preference for four-tnembered ring formation over ftve-membered ring formation is observed, as is a preference for insertion into equatorial rather than axial C-H bonds. 

Lactams substituted only in the 3 position cannot be prepared by the present procedure, since the lactam formed has the nitrogen of the chlorosulfonyl isocyanate attached to the more highly substituted carbon atom of the olefinic double bond in Markownikoff fashion. 2-Azetidinones substituted in the 3 position only have been prepared by Grignard reagent-catalyzed cyclizations of esters of appropriately substituted /3-amino acids.4,5... 

A base-catalyzed cyclization of esters 57 gave a mixture of 3H-pyrrolizine esters (58a and 58b).14,43 The isomers were separated and the dependence of the ratio of isomer 58a to isomer 58b on the conditions of cyclization has been investigated.44 Generally the isomer with the electron-attracting group in the pyrrole ring seems to be the more stable isomer (see Section III). 

On the basis of data obtained in the previous paragraphs, one can propose that formation of 5-oxoniachrysenes 67 (R2 = H) occurs via the primary O-formylation of 66 followed by cyclization of esters 70 (R2 = R3 = H), which is similar to the Pictet-Gams reaction (80T1279). Obviously, this mechanism can also be applied to the acylation of 66 with R2COOH (R2 does not equal H) in PPA in contrast to the scheme of formation of 2-benzopyrylium cations 30 from benzyl ketones 28 (Section II, C, 2). 

Fig. 26 Electrochemical mediated nickel-catalyzed cyclizations of esters 109...

Dieckmann reaction. Base-catalyzed intramolecular cyclization of esters of dicarboxylic acids to give (3-ketoesters. 

An additional example (Figure 4) of stereochemical control was observed by workers at BMC in cyclization of ester enolates (6). Cyclization of the ethyl ester initiated by sodium t-butoxide in hexane produced a 12 88 ratio of cis traps cyclopropanes. 

Table 2 Influence of the Ligand Bound to Rhodium on the Diastereoselectivity of the Cyclization of Ester 29...

This reaction was first reported by Breckpot in 1923. It is the synthesis of )0-lactam via the cyclization of esters of /3-amino acids with Grignard reagent and is known as the Breckpot -lactam synthesis. This reaction has been modified to form )0-lactam by the treatment of )0-amino acid with Mukaiyama s reagent, or the /3-amino ester with /V-methyl pyridinium salt." ... 

Cyclization of esters of jS-amino acids, where a good yield is obtained only with tertiary C compounds ... 

Cyclization of esters of type (304) is sometimes accompanied by elimination and leads to cyclic derivatives of dehydro-N-hydroxyamino acids, as happens in the case (304) itself which results in formation of l,4-dihydroxy-3,6-diisobutylidene-2,5-dioxopiperazine (305) (140) (Scheme 59). Shin and coworkers (207) obtained unsaturated N-hy-droxydiketopiperazines (307) from a,p-dehydro-halogenoacylamino acids (306) by cycUzation with hydroxylamine in ethanol in the presence of sodium alcoholate (Scheme 60). 

Cyclodehydration of acids 1 can be accomplished with, for example, CH3SO2CI/ NaHCOs [12], cyclization of esters 2 by treatment with a strong base, for example, a Grignard compound or an amide thus, the cyclization of p-aminopropionate (2, R = Ft) to give 3 can be carried out with mesityl-MgBr. 

Fife, T.H., Chauffe, L. General base and general acid catalyzed intramolecular aminolysis of esters cyclization of esters of 2-aminomethylbenzoic acid to phthal-imidine. J. Org. Chem. 2000, 65(12), 3579-3586. 

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