Esters cyclization

With a nickel carbonyl catalyst, hydrochloric acid, and an alcohol the initially formed aHenic ester cyclizes on distillation (198). 

Radical cyclization is compatible with the presence of other functional groups. Treatment of XCH2CON(R)-C(R )=CH2 derivatives (X = Cl, Br, 1) with Ph3SnH and AIBN led to formation of a lactam via radical cyclization. " Cyclization of N-iodoethyl-5-vinyl-2-pyrrolidinone led to the corresponding bicyclic lactam, " and there are other examples of radical cyclization with molecules containing a lactam unit " or an amide unit. Radical cyclization occurs with enamines as well. Photochemical irradiation of A,A-dialIyl acrylamide leads to formation of a lactam ring, and in this case thiophenol was added to generate the phenylthio derivative. Phenylseleno N-allylamines lead to cyclic amines. co-Iodo acrylate esters cyclize to form lactones. " ... 

Several other nucleophilic functional groups can be induced to participate in iodocyclization reactions. t-Butyl carbonate esters cyclize to diol carbonates.79... 

The esters cyclized directly. Thus, when the reaction of 219 with... 

Janetka and Rich (78) have utilized the considerable stability of ruthenium-77-arene systems in the synthesis of cyclic tripeptides as analogs of the protease inhibitor K-13 (cf. 34, Scheme 28). Their approach involves the construction of linear tripeptide complexes (35) using diimide/HOBt coupling of [Ru(Cp)(Boc-p-Cl-PheOH)]PF6 (Cp = 775-C5H5) with the appropriate dipeptide ester. Cyclization of 35 affords the biphenyl ether 36, which on photolysis (350 nm) gives 34. 

The traditional method for preparing activated esters of A -protected dipeptides is combination of the A-protected amino acid with the amino acid ester (Figure 7.16). The latter is obtained by A-deprotection of the diprotected amino acid in an acidic milieu. Coupling is achievable using the carbodiimide, mixed-anhydride, and acyl-azide methods. Success with this approach indicates that the esterified residues react preferentially with the other derivatives and not among themselves. The chain cannot be extended to the protected tripeptide ester because the dipeptide ester cyclizes too... 

Reacting 3-chloro-4-fluoroaniline and ethyl ethoxymethylenmalonate gives the snbsti-tntion prodnct (33.2.15), which upon heating in diphenyl ester cyclizes into ethyl ester of 6-flnoro-7-chloro-l,4-dihydro-3-quinolin-4-on-carboxylic acid (33.2.16). Direct treatment of the prodnct with ethyl iodide in the presence of triethylamine and snbseqnent hydrolysis with a base gives l-ethyl-6-flnoro-7-chloro-l,4-dihydro-3-qninolin-4-on-carboxylic acid (33.2.17). Reacting this with piperazine gives norfloxacin (33.2.18) [70-75]. 

Based on the early racemic synthesis of 4 (cis series), it had already been demonstrated that 2-azetidinone ring closure could be achieved via nucleophilic attack of a lithium amine anion on a (3-ester. Cyclization could be accomplished with other strong bases, but sodium bistrimethylsilylamide was found to effect efficient cyclization without significant racemization at C3. During the search for experimentally convenient bases, it was noted that Noyori (Nakamura et al., 1983) reported that tetrabutylammonium fluoride (TBAF) as well as LiF, KF, and CsF could serve as the base in Aldol reactions. Treatment of 17a or 17b with TBAF trihydrate in THF did not affect cyclization. After much experimentation it was found that addition of A,0-bistrimethylacetamide (BSA) to 19 followed by TBAF addition, effected 2-azetidinone ring closure. Further optimization found that use of catalytic TBAF (< 1%) in methylene chloride afforded near quantitative cyclization. 

Alkyl- or 3-aryl-2,4-oxazolidinediones via photochemical cyclization, ° organonickel-mediated carbonylation, ° cyclization of A-alkenyl-a-acet-amides, ° carboxylation and cyclization of 2-propynamides, °" cyclization of (9-carbamates of a-hydroxy acetic acids and esters,cyclization of a-hydroxy acetamides,and catalytic asymmetric dihydroxylation (ADH) of A-alkenoyl-2-oxazolidinones. ... 

C13H22O2, Mr 210.32 is a mixture of isomers, bpo kPa 102 °C, ng 1.4626, a colorless to pale yellow liquid with rosy, spicy, fruity, and woody odor. For its preparation 3,6-dimethyl-6-hepten-2-one and 7-methyl-6-octen-3-one are treated with ethyl diethylphosphoryl acetate to give a mixture of octadienoic acid esters. Cyclization with sulfuric/formic acid yields the title compounds as a mixture with isomers [134]. With its complex odor picture it is used in fine fragrances for shading. 

Formation of cinnamoyl esters of thiophenols is readily accomplished. These esters cyclize, with elimination of benzene, by the action of aluminum chloride (Scheme 3). An alternative approach, exemplified in Scheme 4, utilizes the ready thermal isomerization of thiochromones to thiocoumarins (see p. 121), the former being derived from phenylthioacrylic esters. ... 

Pyrrolidines piperidines.D Suitably unsaturated a-iodo (or a-bromo) esters cyclize to pyrrolidines or piperidines in the presence of this Pd(0) catalyst and 1,8-bis(dimethylamino)naphthalene (proton sponge). 

Examples of intramolecular transformations209 include dienone-a,(3-unsaturated ester cyclizations, e.g. (275— 276),209a>b and ester-a, p - unsaturated ester annulations, e.g. (277—>278 Scheme 91).209c Pertinent to the success of these multibond formation protocols is the selective use of the initiating carbanion (or enolates), the counter cation and the initial acceptor. 

Tandem Diels-Alder-Nitronic Ester Cyclization Reactions 1122... 

The carbamoyl group in position 7 could be transformed by phosphoryl chloride to a nitrile group/4 4-Oxo-4f/-pyrido[l,2-u]pyrimidine-7-carboxy-lic acids were esterified by various methods and the esters cyclized to the tricyclic compounds (279) by treatment with trimethylsulfoxonium iodide in dimethyl sulfoxide in the presence of sodium hydride.60... 

Certain enamino esters cyclize at high temperatures to quinolines (Scheme 151).282... 

Benzyl esters, cyclization-hydrosilylation, 11, 386-387 Benzyl ethers, cyclization-hydrosilylation, 11, 386-387 Benzyl groups, C-H bond silylation, 10, 240 Benzylic alcohols, catalytic alkylation, 11, 146 Benzylic carbon-hydrogen bonds borylation, 9, 174... 

Heliannuols are not an exception. Only one year later following the publication of heliannuol A, the first total synthesis of the racemic (+)-heliannuol A using the coumarin 18 as starting material was published.7 A key step in this synthesis was the ring closure achieved by two different methods intramolecular Julia coupling of the sulfone 19 and sulfone ester cyclization of the alternative sulfone 20 (Fig. 5.4.A). Desulfonation and demethylation yielded the desired (+)-heliannuol A. 

Enantioselective alkylation ofta-formyl esters. In the presence of a catalytic amount of the N,N-dibutyl derivative (2) of 1, dialkylzincs add to the formyl group of esters such as 3 or 4 to form (S)-4- or -5-hydroxyalkanoic esters. These esters cyclize to optically active alkyl-substituted lactones. 

If cyclization is to be followed by decarboxylation, a cunning plan can be set in motion. Addition of an amine by an S 2 reaction to an a halo-ester followed by conjugate addition to an unsaturated ester gives a substrate for Claisen ester cyclization. 

Conjugate addition followed by Claisen ester cyclization gives cyclic diketones... 

When sulfuric acid is used in the cyclization of 5, an a-pyrone is the main product, being formed in 71% yield, with small amounts of furan-2,3,5-tricarboxylic ester. Cyclizations of the formyl derivative are more satisfactory.67 From ethyl levulate and 4,4-diethoxy -butyronitrile51 products were obtained as follows ... 

Several other transannular lactonizations and reductions have been reported to proceed in high overall yields. Also other acid derivatives, such as amides and esters, cyclize to form lactones. Alkynoic acids have been lactonized to y-alkylidene-y-lactones in good yield, e.g. the conversion of (31) to (32 equation 29). Unfortunately the vinyl selenide product can isomerize from ( ) to (Z) in a secondary process. Analogous lactam formation is also known. Unsaturated amides, when cyclized with benzenese-lenenyl halides, produce good yields of lactams or iminolactones depending upon the alkene utilized. The amide (33) cyclizes to the iminolactone (34), producing a mixture of stereoisomers (65 35 Scheme 5). The amide (35) is cyclized to lactam (36) in moderate yield. 

Cyclization epoxy -fceto esters. Treatment of I with BF3 etherate effects cyclization to the S,8-dioxabicyclo[3.2.1]octane 2 in higli yield. This basic skeleton had been encountered in several sex pheromones of bawk beetles such as frontalin (3), which can be synthesized readily by the -keto ester cyclization, since the carboxylic acid corresponding to 2 is readily decarboxylated when heated at 220°. ... 

An improved yield of diethyl 1, l-cyclobutanedicarbojtylate is obtained by preparing the intermediate haloalkylmalonic ester, Br(CH,)3CHfCOjCjH5)j, by the "reverse addition of hydrogen bromide to allylmalonic ester. Cyclization is then effected by sodium ethoxide. ... 

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