Cyclization, regiospecificity

Cyclopentenone annelation, The isomeric adducts 1 of 2-methylcyclohexanone and propargyi alcohol both cyclize regiospecifically to the hydrindanone 2 (70%... 

Good yields of 2,4-diaminoquinolines are obtained through either Lewis acid- or base-induced cyclization of 2-amidinobenzonitriles (20) (58). The method avoids both the harsh conditions and lack of regiospecificity characteristic of earlier preparations. 

The Lewis acid-catalyzed cyclization of 3-anaino-2-alkerLirnines (21) leads to a wide variety of alkyl- and aryl-substituted quinolines (59). The high regiospecificity and the excellent yields obtained make this process promising. 

The reaction of a ,)3-alkynic nitriles (317) with hydroxylamine gave the 5-aminoisoxazoles (318) regiospecifically, whereas in the presence of sodium hydroxide the 3-aminoisoxazoles (319) were obtained exclusively (66CPB1277). Similarly, the course of the cyclization of arylhydrazones (320) was influenced by a change in the base employed (75JOC2604). 

A 1 1 adduct from diphenylsulfilimine and a benzoylacetylene underwent an intramolecular cyclization reaction to give an isoxazole in good yield (equation 40). Similarly, the 1 1 adduct from iodoazide and chalcone gave 3,5-diphenylisoxazole (equation 41). These two approaches to regiospecific isoxazole synthesis are of little practical significance. Additional examples of the (OCCCN) reaction are given in equations (42) and (43). 

Binucleophiles give regiospecific addition to trifluoromethylacetylene with and without subsequent cyclization. Initial attack by the softer nucleophile occurs preferentially at the carbon p to the trifluoromethyl group [6] (equation 7). 

Recently, Burger devised an improved method of carrying out mild, regiospecific cyclizations that involve an intermediate that acts as a synthon for a nitrile ylide of HCN [47 (equation 48). With this methodology, cycloadditions with activated alkenes, alkynes, and azo compounds were earned out [47] (equation 49). All such reported reactions were regiospecific and had the same orientational preference... 

Reaction of 2-methoxytetrahydropyrrole with dioxalane-2,4-dione in presence of Et3N in benzene followed by treatment with MeONa in methanol afforded the monocyclic intermediate 185. Its treatment with BuLi followed by perfluorobenzoyl chloride gave 186 whose hydrolysis gave 187 which possess low or no antibacterial activity (96PHA805). Regiospecific intramolecular cyclization of 188 with sodium hydride yielded 189 as ester whose hydrolysis gave the respective acid (87JHC1537) (Scheme 35). 

The base-catalyzed Michael addition of 2-chlorocyanoacetate to a,p-unsaturated ketones or aldehydes affords 5-oxopentenenitrile derivatives. In the presence of anhydrous HCl, these compounds cyclize to yield 2-chloro-3-pyridinecarboxylates. The process is highly regiospecific and usefiil in the synthesis of 2,Xdisubstituted pyridines <95T(51)13177>. 

The regiospecificity of intramolecular palladium-induced cyclization of o-allylphenols is determined by the precise nature of the catalyst. A mixture... 

A report on a regiospecific 6-exo radical cyclization for the generation of lactams 173 highlights a remarkable halogen-substitution effect on the direct reactions of unsaturated N-H amides on vinylic halogen substituents <06OL2647>. 

A regiospecific strategy to A-7-substituted purines 65 and its application to a library of 2,6,8-trisubstituted purines has been reported. The three-step synthetic strategy involves cyclization reactions of suitably substituted pyrimidines 63 with either a carboxylic acid or an aldehyde <06JC0410>. 

These reactions were proposed to proceed via electrophilic attack on the enol by the SN reagents at N followed by cyclization either via a second enol as in compound 151 or by cyclization onto the more reactive carbonyl <1997J(P1)2831>. Unsymmetrical 1,3-diketones can give a mixture of regioisomers if both carbonyls have similar reactivities however, aroylacetones react regiospecifically to afford only the 3-aroyl-4-alkyl-l,2,5-thiadiazoles 154 (R = Me). 

Enamines 187 with electron-withdrawing groups in the /3-position are converted into thiadiazoles 188 in moderate yields (50-60%) on treatment with either tetrasulfur tetranitride antimony pentachloride complex <2000H(53)159> or trithiazyl trichloride <2001J(P1)662> (Equation 38 Table 12). Cyclization onto electrophilic /3-substituents was not observed, and thus the procedure offers a regiospecific synthesis of 4-substituted-3-aroyl-l,2,5-thiadiazoles. 

In a similar manner, starting from 2-methylchloride-naphtho[l,8-de][l,2,3]triazine and magnesium, via a novel sonication-promoted Barbier reaction, an a-aminomethyl carbanion equivalent is generated which reacts in situ with a variety of carbonyl compounds. Subsequent catalytic hydrogenolysis of the triazine moiety yields the corresponding amines <00TL4685>. Sterically controlled regiospecific cyclization of aldose-5-ethyl-l,2,4-... 

The intramolecular cyclization of l,2-dien-7-ynes and l,2-dien-6-ynes regiospecifically affords the corresponding titanacycles, which react with protons, carbon monoxide, aldehydes, or imines to give single products, as shown in Eqs. 9.56 and 9.57 [102], As the formation of titanacycles and their subsequent reaction with externally added reagents such as carbon monoxide (Eq. 9.56) or an aldehyde (or imine) (Eq. 9.57) proceeds with excellent chirality transfer, this represents a new method for synthesizing optically active cyclopentane derivatives from optically active allenes [102]. 

Grigg discovered that a 5-exo-dig Pd-catalyzed cyclization of IV-acetylenic-o-haloanilines 291 to give 3-exo-alkylidene indolines 292 occurs in the presence of a hydride source, such as formic acid [346]. The reaction is stereoselective and regiospecific. 

Sonogashira reactions of both a-halothiophenes [117] and P-halothiophenes [118] proceed smoothly even for fairly complicated molecules as illustrated by the transformation of brotizolam (134) to alkyne 135 [119]. Interestingly, 3,4-bis(trimethylsilyl)thiophene (137), derived from the intermolecular cyclization of 4-phenylthiazole (136) and bis(trimethylsilyl)acetylene, underwent consecutive iodination and Sonogashira reaction to make 3,4-bisalkynylthiophenes [120], Therefore, a regiospecific mono-i/wo-iodination of 137 gave iodothiophene 138, which was coupled with phenylacetylene to afford alkynylthiophene 139. A second iodination and a Sonogashira reaction then provided the unsymmetrically substituted 3,4-bisalkynylthiophene 140. 

The base-catalyzed condensation of azides with activated methylene compounds is a well-established route to IJT-triazoles. In particular, it is the best route to triazoles bearing a 5-amino or hydroxy substituent and an aryl or carbonyl-containing function in the 4-position. The addition is regiospecific. The reaction is a stepwise one, since anomerism of glycosyl azides has been observed in their reaction with activated methylene compounds, indicating the presence of an intermediate. The mechanism can be envisaged as a nucleophilic attack by the car-banion on the terminal nitrogen of the azide, followed by cyclization to a... 

Amino-1,2,3-triazoles with a substituent at the 4-position have been prepared (i) from azides and active methylene nitriles (ii) from azides and ynamines (iii) from diazomethane and carbo-diimides (iv) from azides and 1,1-diaminoethenes and (v) from the rearrangement of 3-hydrazono-1,2,4-oxadiazoles. Among these, the first method, a regiospecific process, is the most versatile and convenient although it is suitable only for 5-NH2-substituted triazoles. Other methods are used to prepare 5-NHR , 5-NR R - and 5-NHCOR-substituted triazoles. Intramolecular cyclization of suitable precursors also gives 5-aminotriazoles. For example, a-imino-a-piperidyl phenylhydrazones (838), in the presence of copper acetate, give 5-piperidyl-triazoles (839) (Equation (85)) <94H(38)739>. 

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