Intramolecular acyl

Cydopentane reagents used in synthesis are usually derived from cyclopentanone (R.A. Ellison, 1973). Classically they are made by base-catalyzed intramolecular aldol or ester condensations (see also p. 55). An important example is 2-methylcydopentane-l,3-dione. It is synthesized by intramolecular acylation of diethyl propionylsucdnate dianion followed by saponification and decarboxylation. This cyclization only worked with potassium t-butoxide in boiling xylene (R. Bucourt, 1965). Faster routes to this diketone start with succinic acid or its anhydride. A Friedel-Crafts acylation with 2-acetoxy-2-butene in nitrobenzene or with pro-pionyl chloride in nitromethane leads to acylated adducts, which are deacylated in aqueous acids (V.J. Grenda, 1967 L.E. Schick, 1969). A new promising route to substituted cyclopent-2-enones makes use of intermediate 5-nitro-l,3-diones (D. Seebach, 1977). 

Intramolecular acylation of ketones yields cyclic p diketones when the ring that is formed is five or six membered... 

Chiral Lactones and Polyesters. Similar to intermolecular reactions described previously. Upases also catalyze intramolecular acylations of hydroxy acids the reactionsults in the formation of lactones. 

Interesting results have been obtained in intramolecular acylation reactions involving pyrrole and thiophene derivatives. A muscone synthesis involves selective intramolecular acylation at a vacant a-position (Scheme 18) (80JOC1906). In attempts to prepare 5,5-fused systems via intramolecular acylation reactions on to a jS-position of a thiophene or a pyrrole, in some cases ipso substitution occurs with the result that rearranged products are formed (Scheme 19) (82TH30200). 

Ring closures based upon electrophilic processes are uncommon. The cationic cyclization in Scheme 29a proceeds via transformation of the commencing oxime into a nitrilium ion (81CC568). Schemes 29b (82CB706) and 29c (82CB714) exemplify the application of intramolecular acylation. 

Ring formation by intramolecular acylation is exemplified by the isatin syntheses shown in Schemes 37c and 37d (75AHC(18)l). 

Benzo[b]thiophene-2,3-quinone, 5-chloro-oxidation, 4, 824 Benzothiophenes, 4, 863-934 biological activity, 4, 911-913 intramolecular acylation, 4, 761 mass spectrometry, 4, 739 metabolism, 1, 242 phosphorescence, 4, 16 reactivity, 4, 741-861 spectroscopy, 4, 713-740 structure, 4, 713-740 substituents reactivity, 4, 796-839... 

Propionic acid, 2-bromo-3-(3-indolyl)-methyl ester rearrangement, 4, 279 Propionic acid, 3-(3,4-dimethyoxyphenyl)-dihydrocoumarin synthesis from, 3, 848 Propionic acid, indolyl-synthesis, 4, 232 Propionic acid, 3-(l-indolyl)-sodium salt pyrolysis, 4, 202 Propionic acid, 3-(3-indolyl)-intramolecular acylation, 4, 220, 221 Propionic acid, 3-phenoxy-chroman-4-one synthesis from, 3, 855 Propionic acid, 3-(3-phenylisoxazoI-5-yl)-bromination, 6, 25... 

Propionic acid, pyrrolyl-synthesis, 4, 232 Propionic acid, 3-(2-pyrrolyl)-intramolecular acylation, 4, 221 Propylamine, oxadiazolyl-synthesis, 6, 445... 

Pyrrole, 1 -benzyl-2-(2-carboxybenzoyl)-intramolecular acylation, 4, 221 Pyrrole, l-benzyl-2,5-dichloro-3,4-diformyl-reactions... 

Carboxylic acids and their anhydrides acy late a variety of benzene derivatives, fused ring systems, and heterocyclic compounds. An improved procedure for the preparation of l,4-difluoroanthracene-9,10-dione involves reacting phthalic anhydride and 1,4-difluorobenzene to prepare an intermediate carboxylic acid [35] Intramolecular acylation in polyphosphonc acid completes the synthesis (equahon 24). 

The Reforrnatsku reaction of a-halogenated carboxylic esters with silylated cyanohydrins combined with an intramolecular acylation reaction gives fluorinated derivatives of tetronic acid [28] (equation 17) It is noteworthy to mention that this particular reaction sequence only proceeds with ultrasonic irradiation A very... 

Dicarboxylic acid dichlorides with less than seven carbon atoms do not react to give tetraketones similar to 117, but instead undergo an intramolecular acylation (72) to give on hydrolysis the vinylogous acid anhydride (118), e.g., from succinyl chloride and the enamine (113). 

An interesting rearrangement which is based on the intramolecular acylation of an enamine by an ester is found in the aromatization of the adduct derived from N-methylpyrrole and an acetylenedicarboxylic ester (407,408). 

In one particular example, an interesting intramolecular acylation occurred. Reduction of cis-iVi-acetyl-o-nitrobenzylideneoxindole (55) gave rise to a cyclic hydroxamic acid, assigned structure 56. 

Acylation of j8-carboline under Schotten-Baumann conditions yields the ind-N-, cy derivative. An intramolecular acylation of the cis-isomer of 278 to yield 279 has been carried out (see Section V). On the other hand, intramolecular acylation at the pyr-N of a j8-carboline, in the instance of the spontaneous cyclization of 281 to the pentacyclic compound 282, has been reported. 

Intramolecular acylation of suitably 1-substituted 1,2,3,4-tetra-hydro-/8-carbolines has been studied. It has been stated that... 

With tetrachloroethane as solvent, two modes of ring-opening occur, leading to the formation of 2-benzamidoindenone (20), by intramolecular acylation [Eq. (14)], and l-phenylisoquinoline-3-carboxylic acid (21), by intramolecular imidoylaiion [Eq. (15)]. 

The. synthesis starts with the Stobbe condensation of diethylsuccinate and 3,4-dichloroben-zophenone (13). The product (14) is hydrolyzed and decarboxylated to a cis-trans mixture of olefins (15). This last is reduced using a Pd/C catalyst and then undergoes unidirectional Friedel-Crafts intramolecular acylation into the more reactive ring to produce substituted tetralone 16. 

Cyclopentanones from carboxylic acids by intramolecular acylation of alkyl-silanes... 

In the first step, catalyst 64c attacks ketene 66 to form a zwitterionic enolate 71, followed by Mannich-type reaction with imine 76 (Fig. 40). A subsequent intramolecular acylation expels the catalyst under formation of the four-membered ring. Utilizing 10 mol% of 64c, N-Ts substituted (3-lactams 77 were prepared from symmetrically as well as unsymmetrically substituted ketenes 66, mainly, but not exclusively, with nonenolizable imines 76 as reaction partners [96]. Diastereos-electivities ranged from 8 1 to 15 1, yields from 76 to 97%, and enantioselectivities from 81 to 94% ee in the case of aliphatic ketenes 66 or 89 to 98% ee for ketenes bearing an aromatic substituent. Applying complexes 65 or the more bulky and less electron-rich 64b, ee values below 5% were obtained. 

Intramolecular acylations are very common, and the normal conditions involving an acyl halide and Lewis acid can be utilized. One useful alternative is to dissolve the carboxylic acid in polyphosphoric acid (PPA) and heat to effect cyclization. This procedure probably involves formation of a mixed phosphoric-carboxylic anhydride.54... 

A classical procedure for fusing a six-membered ring to an aromatic ring uses succinic anhydride or a derivative. An intermolecular acylation is followed by reduction and an intramolecular acylation. The reduction step is necessary to provide a more reactive ring for the second acylation. 

In Entry 10, intramolecular acylation is followed by dehydrohalogenation. Entries 11 and 12 illustrate the use of polyphosphate ester. The cyclization in Entry 13 is done in neat methanesulfonic acid. 

Fused octahydrocycl[3.2.2]azines of the type 392 are obtained by tandem cycloadditions of pyridinium phenacylide with iV-substituted maleimides <1989JOC420>, and other types of fused octahydrocyclazines, viz. 394, result from the attempted preparation of the enamines 393, since these are unstable and undergo intramolecular acylation <1999T1763> (Scheme 114). 

The indolizinoquinoline 106 can be prepared by intramolecular acylation of the precursor 105. The organolithium derivative of 105 reacts intramolecularly with the amide this Parham-type reaction gives the triheterocyclic product in reasonable yield, and higher yields are obtained when the Weinreb-type methoxyamide (Rz = OMe) is used (Equation 21) <20030L1115>. 

Intramolecular acyl alkylation affords cyclic carbene ligands, e.g., (t 5-C5H5)Ru(CO)2 + C1CH2CH2CH2CC1 -> (t 5-C5H5)(CO)2RuCCH2CH2CH2C1... 

The preparation of 3-vinylpyrroles was investigated utilizing the Horner-Wads worth-Emmons reaction with 3-formyl-lV-tosylpyrrole <06S1494>. The intramolecular acylation of pyrrole-2-Weinreb amides provided access to novel indolizinone derivatives <06T6182>. The amidation of pyrrole-2-carbonyl chloride was utilized as a key step in the preparation of pyrrole-oxazole analogue 90 of the insecticide Pirate <06S1975>. 

A reasonable mechanism for their formation starts with the primary adduct 339, which is capable of ring-opening to the ketene 340 this can either be trapped by addition of water (337) or undergo intramolecular acylation followed by dehydrogenation (338). 

---