Ring closure catalysed

The base-catalysed reaction of a-bromo-a,P-unsaturated ketones with aliphatic nitro compounds leads to 2-isoxazoline A-oxides by tandem conjugate addition-ring closure (Scheme 5) <95JOC6624>. A -Acyl-3-isoxazolin-5-ones are transformed into oxazoles by photolysis or by flash vacuum pyrolysis (Scheme 6) <96TL675>. 

Indole systan 168 has been prepared from a ring closure reaction of dihydroisoqui-noline derivative 167 catalysed by a NHC-Pd system (Scheme 5.44) [49], The product 168 was prepared from an intramolecular Buchwald-Hartwig coupling and was used in the total synthesis of rac-mangochinine 169. 

Scheme 5.44 Ring closure reaction of dihydroisoquinoline derivative catalysed by a NHC-Pd system...

R= Ph, 4-Me-Ph, 4-CI-Ph, Naphtyl, 3-MeO-Ph, 4-F-Ph Scheme 5.45 NHC-Pd catalysed ring closure of o-bromobenzyl ketones... 

Bicyclic imidazolidin-2-ones 173 have been prepared in good yields and high diastereoselectivity (Scheme 5.46) [51], The ring closure of MAT -disubstituted ureas 172 was catalysed by [AuCl(lPr)] complex in presence of a silver salt. 

The acid-catalysed ring-closure of divinyl ketones to cyclopentenones (equation 6), the Nazarov reaction6-8, represents a conrotatory electrocyclization of 4jr-cyclopentadienyl cations. The conrotatory course of the reaction was confirmed for the case of the dicyclo-hexenyl ketone 7, which yielded solely the tricyclic ketone 8 on treatment with phosphoric acid (equation 7)3b. Cycloalkanocyclopentenones 10 with c/s-fused rings are obtained from the trimethylsilyl-substituted ketones 9 (n = 1, 2 or 3) and iron(III) chloride and... 

The stereoselectivity of the thermal ring-closure of the dodecatrieneones 42 is determined by the nature of the remote group R. trans-Fused products 43 predominate over cw-products 44 and their ratio increases as R varies from MeO through Me to H (equation 29). If the reactions are catalysed by diethylaluminium chloride only fraws-compounds are formed. The homologues 45 behave similarly34. In contrast, the 7-azadeca-l,3,9-trienes 46 (X, Y = H2 or O) yield more of the cis- than the traws-fused compounds, regardless of the nature of X and Y (equation 30)35. 

The octalinyl ester 166 is produced in excellent yield when the butenylcyclohexenol 165 is treated with formic acid at room temperature (equation 80)89. The dimethyl analogue 167 reacts similarly to give 168 (equation 81)90. The trifluoroacetic acid-catalysed ring-closure of the ketene thioacetal 169 to give a 1 2 mixture of the cis- and trans-ketones 170 and 171 (equation 82) has been reported91. 

The tetracyclic alcohol 179 is produced by the action of boron trifluoride etherate or tin(IV) chloride on the oxirane 178 (equation 85)95. A similar cyclization of the oxirane 180 yields DL-<5-amyrin (181) (equation 86)96. In the SnCLt-catalysed ring-closure of the tetraene 182 to the all-fraws-tetracycle 183 (equation 87) seven asymmetric centres are created, yet only two of sixty-four possible racemates are formed97. It has been proposed that multiple ring-closures of this kind form the basis of the biosynthesis of steroids and tetra-and pentacyclic triterpenoids, the Stork-Eschenmoser hypothesis 98,99. Such biomimetic polyene cyclizations, e.g. the formation of lanosterol from squalene (equation 88), have been reviewed69,70. 

Diisobutylaluminium hydride catalyses the ring-closure of various dienes. It is proposed that the process involves addition of the aluminium hydride to a terminal double bond, followed by ring-closure and, finally, elimination of the catalyst (equation 106). Thus 1,5-hexadiene gives methylenecyclopentane (213) (equation 107), 1,6-heptadiene gives methylenecyclohexane (214) (equation 108), 4-vinylcyclohexene gives bicyclo[3.2.1]oct-2-ene (215) (equation 109) and the spiro compound 217 is obtained from 5-methylene-l,8-nonadiene (216) (equation 110)112. 

The diester 226 undergoes ring-closure to the methylenecyclopentane derivative 227 in the presence of a catalytic amount of chlorotris(triphenylphosphine)rhodium in boiling chloroform saturated with hydrogen chloride. In contrast, if the reaction is catalysed by palladium(II) acetate, the isomeric cyclopentene 228 is produced (equation 115)118. 

The metal-catalysed olefin metathesis (equation 122) when applied to dienes results in ring-closure and expulsion of an olefin (equation 123). Thus the molybdenum carbene complex 241 promotes the decomposition of the 1,6-heptadiene derivative 242 to a mixture of the cyclopentene 243 and ethylene (equation 124)122. An analogous reaction of the alcohol 244 gives 245 (equation 125), and 4-benzyloxy-l,7-decadiene (246) affords the cyclohexene 247 and 1-butene (equation 126). These transformations, which occur in benzene at room temperature, proceed in excellent yields122. 

The main tables are designated by a letter and a number (a full list is given in the Contents at the beginning of this chapter). Tables in the text, which mostly contain effective molarities taken from the main tables, are designated by a number only. Every individual reaction is identified by a reference letter and two numbers. Thus B.6.3 refers to the base-catalysed cyclization of cyclohexyl 2-hydroxyethyl phosphate which is the third entry in Table B.6. The EM for this reaction is given in Table 10 in the discussion of the effects of alkyl substitution on ring-closure, and the reference number quoted there. Full details of the calculation of the EM, the rate constant on which it is based, the conditions used and the authors concerned can then be found by consulting Table B.6. 

In reactions where several different outcomes are possible, the final product distribution reflects the relative free energies of each transition state when the reaction is under kinetic control (Schultz and Lemer, 1993). Baldwin s rules predict that for acid-catalysed ring closure of the hydroxyepoxide [65] the tetrahydrofuran product [66] arising from 5-exo-tet attack will be preferred... 

Fig. 25 The monoclonal antibody 26D9, generated to the jV-oxide hapten [67], catalysed the 6-exo-tet ring closure of [65] regioselectively to yield the disfavoured tetrahydropyran product [68]. This is a formal violation of Baldwin s rules, which predicts a 5-exo-tet spontaneous process to generate tetrahydrofuran derivative [66].

A phase-transfer catalysed nucleophilic displacement reaction on chloro-acetanilides by cyanate ions, followed by ring-closure (Scheme 5.10), provides a simple and viable synthesis of hydantoins [41], The formation of the hydantoins is inhibited by substituents in the orf/to-position of the aryl ring, but the addition of potassium iodide, or tetra-n-butylammonium iodide, generally increases the overall rate of formation of the cyclic compounds, presumably by facilitating the initial nucleophilic substitution step. 

The catalysed A/-alkylation of the potassium salt of sulphoximines in l, 2-dimethoxyethane produces yields in excess of 90% [48]. Similarly, azacrown ethers have been synthesized by alkylation of bis(tosyIamino)alkyl ethers under catalysed basic two-phase conditions [49] (Scheme 5.12). The yields of the cyclic products (Table 5.24) are influenced by the choice of the alkali metal hydroxide employed, suggesting that there is a degree of template control in the ring closure step. This is not the case in the analogous reaction of p-toluenesulphonamide with a, co-dihaloalkanes [50], which leads to the formation of a mixture of l l and 2 2 cyclic products... 

Catalysed alkylation of tosylmethylisocyanate (TOSMIC) [63, 64] has extended its versatility in the preparation of l, 4-dicarbonyl compounds and as a l, 3-dipolar precursor for the synthesis of heterocyclic compounds. The alkylation reactions should not be conducted in carbon disulphide, as nucleophilic attack by the methylene group on the carbon disulphide leads, after ring closure and S-alkylation, to a 4-alkylthio-1,3-thiazole system [65]. 

The formation of cyclopropanes from 7C-deficient alkenes via an initial Michael-type reaction followed by nucleophilic ring closure of the intermediate anion (Scheme 6.26, see also Section 7.3), is catalysed by the addition of quaternary ammonium phase-transfer catalysts [46,47] which affect the stereochemistry of the ring closure (see Chapter 12). For example, equal amounts of (4) and (5) (X1, X2 = CN) are produced in the presence of benzyltriethylammonium chloride, whereas compound (4) predominates in the absence of the catalyst. In contrast, a,p-unsatu-rated ketones or esters and a-chloroacetic esters [e.g. 48] produce the cyclopropanes (6) (Scheme 6.27) stereoselectively under phase-transfer catalysed conditions and in the absence of the catalyst. Phenyl vinyl sulphone reacts with a-chloroacetonitriles to give the non-cyclized Michael adducts (80%) to the almost complete exclusion of the cyclopropanes. 

Not surprisingly, electron-poor systems react with chloroform, bromoform and other haloalkanes under basic conditions by Michael-type addition of the trihalomethyl anion to the C=C bond. However, a subsequent base-catalysed ring closure to give the cyclopropane derivatives frequently occurs [e.g., 6,7,26,31,39,72, 84,93,111, 113, 115, 118]. 

Diols generally react with dichlorocarbene to produce a mixture of alkenes and chlorinated cyclopropanes or chloroalkanes, depending on the reaction conditions whereas, under phase-transfer catalysed conditions, the major products are the alkenes and epoxides produced by ring closure of the initial adduct (Scheme 7.20) [14]. When an excess of chloroform is used, further reaction of the alkenes with dichlorocarbene produces the cycloadducts. In addition to the formation of the alkene and epoxide, 1,2-dihydroxycyclooctane yields cyclooctanone, via a 1,2-hydride shift within the intermediate carbenium ion. 

The stereoselective epoxidation of chalcones, followed by acid-catalysed ring closure and concomitant cleavage of the epoxide ring, provides a very efficient route to chiral flavon-3-ols and, subsequently, by borohydride reduction to produce flavan-3,4-diols [13, 14], It has been shown that diastereoselective reduction of the chiral flavon-3-ols by sodium borohydride in methanol yields the trans-2,3-dihydroxy compounds, whereas borohydride reduction in dioxan produces the cis-isomers [14] the synthetic procedure confirms the cis configuration of the 2,3-hydroxy groups of naturally occurring leucodelphinidins [14]. 

Results of a study of acid-catalysed epimerization of indolo [2,3-a]quinolizidine derivatives support a mechanism involving nitrogen lone pairs in an eliminative ring opening-ring closure. ... 

The transition metal catalyzed synthesis of five membered heterocycles, particularly of condensed ring systems, has attracted considerable attention. The ease of the formation of five membered rings has been utilised both in intramolecular ring closure processes, and in the combination of two (three) fragments through the formation of a carbon-carbon and a carbon-heteroatom bond. This chapter is dedicated to examples, where the construction of the five membered heterocycle is achieved in a transition metal catalysed step. 

The facile formation and ring closure of enamines has also been exploited in the solid-phase preparation of indolecarboxylates. Attachment of 2-iodoaniline or 2-bromoaniline to the resin in the form of an or-anilino-acrylate followed by the palladium catalysed formation of the five... 

The pyrrole ring can also be constructed starting from an 7V-vinyl-2-halobenzoic amide. The /V-(2-iodobcnzoyl)-1,4-dihydropyndine derivative shown in 3.19. underwent palladium catalysed ring closure to give a condensed isoindolone derivative. The use of formic acid as co-solvent led to the reduction of the intermediate palladium complex formed in the insertion step, instead of / -hydride elimination. The transfer of the stereochemical information from the starting material to the product was poor.25... 

Members of the retinoid natural product class, containing a quaternary benzylic stereocenter, were prepared by the ring closure of allyl-arylethers. The palladium catalysed process in the presence of sodium formate led to the formation of a partially reduced benzofurane derivative through an insertion-hydride capture reaction sequence (3.24.), The coupling, which was run in the presence of a silver-zeolite, showed acceptable enantioselectivity when... 

The carbon skeleton of natural product galanthamine was prepared by the ring closure of an enantiopure aryl-cyclohexenyl ether. The transformation, run in the presence of a palladium-dppp catalyst and silver carbonate, led to the diastereoselective formation of the tricyclic product (3.25.). It is worth mentioning, that the chiral information in the ether intermediate was introduced in the palladium catalysed Tsuji-Trost reaction (N.B. the synthetic approach depicted in 3.13. and 3.25. are much alike).31... 

The transition metal catalysed formation of five membered heterocycles through the insertion of a triple bond has also been explored. o-Halophenyl-alkynylamines, propargylamines and propargyl-ethers have been subjected to ring closure reactions. These processes, however also require the presence of a second, anionic reagent, which converts the palladium complex formed in the insertion step to the product. 

The palladium catalysed reductive insertion of acetylenes is also viable through the use of formate ions as hydride equivalent (c.f 3.24.), The ring closure of /V-acetylenic-2-iodoanilines gave the corresponding 3-alkylideneindolines in a selective manner (3.27.), demonstrating that the... 

Examples of the formation of sulphur containing heterocycles by similar transformations are quite rare. The palladium catalysed ring closure of S-propargyl-2-iodophenylmercaptane in the presence of formic acid and an amine-base, analogously to phenols and anilines, led to the formation of the partially reduced benzothiophene skeleton, bearing a 3-methylydene function (3.32.),40... 

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