Copper cyclization

Copper Cyclization via aminohalogenation of (195), affording pyrrolidine derivatives (196) at <93% ee, has been reported to proceed upon catalysis with [(7 ,7 )-Ph-box]Cu(OTf)2 in the presence of Pr X (X = I, Br, Cl) as the source of the halogen atom and Mn02. The reaction is believed to proceed via iyn-aminocupration, followed by atom transfer, to form the C-X bond. ... 

Transition-Metal Catalyzed Cyclizations. o-Halogenated anilines and anilides can serve as indole precursors in a group of reactions which are typically cataly2ed by transition metals. Several catalysts have been developed which convert o-haloanilines or anilides to indoles by reaction with acetylenes. An early procedure involved coupling to a copper acetyUde with o-iodoaniline. A more versatile procedure involves palladium catalysis of the reaction of an o-bromo- or o-trifluoromethylsulfonyloxyanihde with a triaLkylstaimylalkyne. The reaction is conducted in two stages, first with a Pd(0) and then a Pd(II) catalyst (29). 

Dehydrogenation of citroneUol over a copper chromite catalyst produces citroneUal [106-23-0] in good yield (110). If the dehydrogenation is done under distiUation conditions in order to remove the lower boiling citroneUal as it is formed, polymerization or cyclization of citroneUal is prevented. 

Another example of the analogy between pyrazole and chlorine is provided by the alkaline cleavage of l-(2,4-dinitrophenyl)pyrazoles. As occurs with l-chloro-2,4-dinitrobenzene, the phenyl substituent bond is broken with concomitant formation of 2,4-dinitrophenol and chlorine or pyrazole anions, respectively (66AHC(6)347). Heterocyclization of iV-arylpyrazoles involving a nitrene has already been discussed (Section 4.04.2.1.8(i)). Another example, related to the Pschorr reaction, is the photochemical cyclization of (515) to (516) (80CJC1880). An unusual transfer of chlorine to the side-chain of a pyrazole derivative was observed when the amine (517 X = H, Y = NH2) was diazotized in hydrochloric acid and subsequently treated with copper powder (72TL3637). The product (517 X = Cl, Y = H) was isolated. 

Cyclization of the diazo compound (108) with a copper catalyst affords the clavulanic acid derivatives (110) and (111), possibly via rearrangement of the sulfur ylide (109) (80H(14)1999). Similar reactions have been reported in the recent literature (80H(14)1967, 81H(16)1305, 80TL31). 

A unique method to generate the pyridine ring employed a transition metal-mediated 6-endo-dig cyclization of A-propargylamine derivative 120. The reaction proceeds in 5-12 h with yields of 22-74%. Gold (HI) salts are required to catalyze the reaction, but copper salts are sufficient with reactive ketones. A proposed reaction mechanism involves activation of the alkyne by transition metal complexation. This lowers the activation energy for the enamine addition to the alkyne that generates 121. The transition metal also behaves as a Lewis acid and facilitates formation of 120 from 118 and 119. Subsequent aromatization of 121 affords pyridine 122. 

Decomposition of the diazonium salt of 2-amino-iV-methyl-iV-3 -pyridylaniline (205) in aqueous acid solution with copper powder at room temperature gave overall yields of cyclized products consisting of a mixture of i id-iV-methyl-3-carboline (206) (47.5%) and ind-N-methyl-jS-carboUne (207) (25.5%), in agreement with the proposed homolytic character of the reaction under these conditions. This constituted the first unambiguous synthesis of a simple 3-carboline derivative. 

The cyclocondensation of iodoaminopyrazole with copper acetylides and the cyclization of aminopyrazolylacetylene with different mutual arrangement in the ring of interacting groups have been studied (83IZV688). 

Cyclization of o-nitroacetylenylbenzenes and cyclocondensation of o-iodonitrobenzene with copper acetylides are widely used to produce isatogens [69JCS(C)2453 69MI2 79JHC221]. The nitro group can be either in the acetylide or in the halide components. 

The cyclization of o-halogenobenzoic acids with copper acetylides mainly leads to the formation of five-membered lactones (66JOC4071 69JA6464) (Scheme 115). Only in the case of the reaction of o-iodobenzoic with CuC=C—n-C3H7 does the formation of a mixture of y- and 5-lactones occur (Scheme 116). 

To verify the generality of the cyclization of iodopyrazolecarboxylic acids, copper p-phenylbenzoylacetylide was used in the reaction with 3-iodo-l-methylpyra-zole-4-carboxylic acid. The assumed intermediate, alkynylpyrazolylcarboxylic acid, has a distribution of the electron density which is the most favorable for closure of the five-membered cyclic ether. However, the reaction leads only to the 5-lactone (Scheme 120). 

Available information on the mechanism of cyclocondensation is rather contradictory. According to one hypothesis, both the condensation of aryl halides with copper acetylides and the cyclization occur in the same copper complex (63JOC2163 63JOC3313). An alternative two-stage reaction route has also been considered condensation followed by cyclization (66JOC4071 69JA6464). However, there is no clear evidence for this assumption in the literature and information on the reaction of acetylenyl-substituted acids in conditions of acetylide synthesis is absent. 

Thus, the vic-acetylenylpyrazolecarboxylic acids are isomerized into pyranoa-zoles in boiling pyridine (20-30 min) with catalytic amounts of copper acetylide. The acetylide condensation of the corresponding iodopyrazolecarboxylic acids is followed by cyclization into the same 5-lactones but with a lower rate (2-8 h). 

An unusual cyclization, which results in carbocycles rather than heterocycles, was described in (69JCS2453). The reaction between o-iodobenzamides and copper phenylacetylides in pyridine leads to indanone (74%) rather than tolane (Scheme 124). 

Another pathway takes place upon cyclization of hydrazides of benzene carboxylic acids in the presence of CuCl in an inert atmosphere in DMF. However, only the cyclization of hydrazide 76 (R = H) in conditions of copper catalysis makes it possible to isolate compound 77 (yield 20%). Other hydrazides of acetylenylbenzoic acids react to give a complex mixture of products (Scheme 132) (85IZV1367 85MI2). 

Whereas the condensation of o-iodonitrobenzene with copper acetylides is accompanied by cyclization into isatogens, neither 4-iodo-3-nitro- nor 5-iodo-4-nitro-l,3-dimethylpyrazole gives cyclized products in conditions of acetylide synthesis. Moreover, nitropyrazolylphenylacetylene, as compared with o-nitrotolane, does not undergo thermal, catalytic, or photochemical isomerization to give the fused five-membered rings. 

The Pschorr reaction, originally applied to the synthesis of phen-anthrene and its derivatives,has been adapted to the formation of new heterocyclic systems.In its original form, it consisted of treating a diazonium salt with copper powder in acid solution in this way, rans-o-amino-a-phenylcinnamic acid was converted into phen-anthrene-9-carboxylic acid, Eq. (20). Variants of the reaction include cyclizations such as that in Eq. (21). The reaction may be horaolytic... 

Hey et al. also cyclized (21) to the a-carboline (22) with copper powder the yield, however, was low, the main product being a salt whose cation was formulated as (23) and which was presumably formed by an ionic reaction. ... 

The branched oligo(arylene)s 37 and 40 can undeigo a further oxidative cyclization with copper(ll) chloride or triflate/aluminum trichloride leading to the formation of large, hitherto unknown polycyclic aromatic hydrocarbons PAHs 41 and 42. 

Cyclization of bromostilbenes 6 to dibenz[/ ,/]oxepins 7 can be achieved by irradiation in excellent yield.102 103 Under solvolytic conditions (60% NaOH, EtOH), the yield is greatly reduced. When a silver salt (AgOAc) is used, however, complete conversion to the tricyclic system is accomplished.102 Tribenz[/>,catalyzed cyclization of biphenyl-2-yl 2 -chlorosulfonylphenyl ether in 44% yield.260... 

The decomposition of 2-(2-phenylphenylsulfanyl)benzenesulfonyl chloride (5) at elevated temperatures leads to the formation of tribenzo[6,c/,/]thiepin(6) in 24% yield by an intramolecular cyclization pathway. Mechanistically, this thermolysis is comparable to the Pschorr reaction (cf. Houben-Weyl, Vol. 5/2b, p 420 Vol. 10/3, p 189) however, copper(I) chloride is now preferred as a catalyst, without any solvent.4 In the thermolysis of 5, 4-phenyldibenzothiophene (7) is formed as a byproduct in 14% yield. Octachloronaphthalene can also be employed as a catalyst however, the yield of 6 is somewhat lower (19%).4... 

The bromo substituent in l-bromo-19-meLhyl-l,l9-dideoxybiladienes- c is not essential for porphyrin formation. When 1-methylbiladiene-ac dihydrobromide or the 1,19-dimethyl-biladienc-ac are heated in refluxing methanol or dimethylformamide in the presence of cop-per(II) salts, the porphyrin copper complexes 13 are formed by oxidative cyclization. The free porphyrins can then be obtained by removal of the copper with acid. A wide range of porphyrins 13 can be prepared by this method. However, a restriction is the accessibility of the starting material with special substitution patterns. 

A completely different concept13 makes use of a highly reduced bilane 5 which is oxidatively cyclized to an isobacteriochlorin 6 with copper(II) acetate. The ring closure is initiated by ester cleavage with trifluoroacetic acid and decarboxylative formylation with trimethyl orthoformate to yield a dialdehyde. One of the aldehyde functions forms the desired methine bridge whereas the other is lost during cyclization. 

Attempts to cyclize the aldehyde 17 in the presence of acid gave only undefined products. Also copper(II)- and cobalt(II)-induced cyclizations yielded the octaethylisocorrolccarbaldc-hyde metal complexes (see Section 1.8.1.) but not the desired isoporphycenes. A breakthrough was achieved by palladium(II)-induced cyclization of 17 which gave a 1 1 mixture of the Z-... 

A third access to isocorroles was found7 when a tetrapyrrole 11 having an acrylaldehyde side chain was cyclized in presence of copper(II) or cobalt(II) salts. In this case isocorrole-9-carb-aldehydes 12 are formed with copper and cobalt in the oxidation state + III. The copper compound can easily be demetaled by hydrochloric acid to yield the metal-free isocorrole. In contrast, the cyclization of the tetrapyrrole in the presence of palladium(II) gives the isopor-phycene (see Section 1.7.1.). 

Carboxylic acids, a-bromination of 55, 31 CARBOXYLIC ACID CHLORIDES, ketones from, 55, 122 CARBYLAMINE REACTION, 55, 96 Ceric ammonium nitrate [Ammonium hexa mtrocerate(IV)[, 55, 43 Chlorine, 55, 33, 35, 63 CHROMIUM TRIOXIDE-PYRIDINE COMPLEX, preparation in situ, 55, 84 Cinnamomtnle, a-phenyl- [2-Propeneni-tnle 2,3-diphenyl-], 55, 92 Copper(l) iodide, 55, 105, 123, 124 Copper thiophenoxide [Benzenethiol, copper(I) salt], 55, 123 CYCLIZATION, free radical, 55, 57 CYCLOBUTADIENE, 55, 43 Cyclobutadieneiron tricarbonyl [Iron, tn-carbonyl(r)4-l,3-cyclo-butadiene)-], 55,43... 

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