Cyclization reactions reductive

Reactions of 3- and 4-piperidone-derived enamines with a dienester gave intermediates which could be dehydrogenated to tetrahydroquinolines and tetrahydroisoquinolines (678). The methyl vinyl ketone annelation of pyrrolines was extended to an erythrinan synthesis (679). Perhydrophenan-threnones were obtained from 1-acetylcyclohexene and pyrrolidinocyclo-hexene (680) or alternatively from Birch reduction and cyclization of a 2-pyridyl ethyl ketone intermediate, which was formed by alkylation of an enamine with a 2-vinylpyridine (681). 

Diastereomeric oxazolidines 88 and 89 (Scheme 8.4.27) were available via 1,4-reduction and cyclization of Zincke product 87, with 88 being the kinetic product under the reaction conditions and 89 (X-ray) the thermodynamically favored isomer in CDCI3 solution. Iterative reductive oxazolidine opening provided 3-aryl piperidine 91, which was readily advanced to (-)-PPP (92), a selective dopaminergic receptor antagonist. ... 

Good yields in conjunctive reductive/addition/cyclization reactions carried out with (R0)2P(0)H compounds were obtained by Parson et al. [28] (Scheme 10). 

In broad terms, the following types of reactions are mediated by the homolytic fission products of water (formally, hydrogen, and hydroxyl radicals), and by molecular oxygen including its excited states—hydrolysis, elimination, oxidation, reduction, and cyclization. 

Cationic palladium complex 121 reductively coupled enynes (Eq. 20) using trichlorosilane as the stoichiometric reductant [71]. This combination of catalyst and silane afforded silylated methylenecyclopentanes such as 122 in good yield from enynes such as 123. Attempts to develop an enantioselective version of this reaction were not successful [71]. When enediyne 124 was cyclized in the presence of trichlorosilane, the reaction favored enyne cycli-zation 126 by a 3 1 ratio over diyne cyclization to 125 (Eq. 21). In contrast, when the more electron-rich dichloromethylsilane was used as the reductant, diyne cyclization product 125 was preferred in a ratio of 4 1 [71]. Selectivities of up to 10 1 for enyne cyclization were observed, depending on the substrate employed [72],... 

Reaction of phenyl vinyl ketone with cyclopentanone under thermal conditions resulted in a diastereomeric mixture of 1,5,9-triketones 374 via a double Michael reaction. Treatment of this mixture with ammonium formate in polyethyleneglycol-200 under microwave irradiation conditions led to the very fast and efficient formation of a 2 1 diastereomeric mixture of cyclopental flquinolizidines 375 and 376 <2002T2189>. When this reductive amination-cyclization procedure was carried out starting from the purified /ra r-isomer of 374, the result was identical to that obtained from the cis-trans mixture, showing the operation of thermodynamic control (Scheme 86). 

Palladium-catalyzed cyclic carboxylation of dienes can be utilized for the synthesis of lactones.2 Polymer-supported Pd catalyst could also be used for this reaction (Scheme 42).61 The reaction is initiated by dimerization of two molecules of diene to give a bis-7r-allylpalladium intermediate such as 123. The incorporation of C02 takes place at the internal position of an allyl unit to afford the 7r-allylpalladium carboxylate 124 which, after reductive elimination/ cyclization, yields the (5-lactone 121 (Scheme 43). 

Interestingly, experimental results indicate that pathway II might be operative in some ruthenium(n)-catalyzed [5 + 2]-reactions. Cyclized products implicating /3-hydride elimination and subsequent reductive elimination from ruthenacyclopentenes have been reported (Scheme 17).26 A direct comparison with rhodium catalysts using these specific substrates has not been reported. 

Furthermore, the copper-mediated SN2 substitution reaction is not restricted to carbon-carbon bond formation, as can be seen form the synthesis of silylallenes [15], stannylallenes [16] and bromoallenes [17] using propargylic electrophiles and the corresponding heterocuprates. The resulting allenes are often used as intermediates in target-oriented synthesis, e.g. in cyclization and reduction reactions [15-17]. 

In almost the same manner, tandem hydroformylation/aldol condensation aldol condensation of ketoolefins, such as p,y-unsaturated ketones, gives a single cyclization product under acid catalysis. Similar to the stepwise reaction, the in situ generated aldehyde preferentially acts as the electrophilic carbonyl component, while the ketone acts as the nucleophilic enol to form the five-membered ring product. Subsequent dehydration and hydrogenation of the resulting enone readily occurs under the reductive reaction conditions used (Scheme 30) [84],... 

In a related study, the oxidation-reduction sequence was carried out in the presence of an olefin (Scheme 21). Two products were formed. The major product resulted from the net reduction of the carboxylic acid to an aldehyde. The minor product resulted from trapping of the radical anion intermediate generated from the reduction reaction by the olefin. It should be noted that, in the absence of a trapping group, the acid can be selectively reduced to the aldehyde without any over-reduction. Although not in the scope of this review, this is a very useful transformation in its own right [35]. At this time, the yields of the cyclized products from the cyclization reaction of the radical anion with the olefin remain low. 

Various transition metals have been used in redox processes. For example, tandem sequences of cyclization have been initiated from malonate enolates by electron-transfer-induced oxidation with ferricenium ion Cp2pe+ (51) followed by cyclization and either radical or cationic termination (Scheme 41). ° Titanium, in the form of Cp2TiPh, has been used to initiate reductive radical cyclizations to give y- and 5-cyano esters in a 5- or 6-exo manner, respectively (Scheme 42). The Ti(III) reagent coordinates both to the C=0 and CN groups and cyclization proceeds irreversibly without formation of iminyl radical intermediates.The oxidation of benzylic and allylic alcohols in a two-phase system in the presence of r-butyl hydroperoxide, a copper catalyst, and a phase-transfer catalyst has been examined. The reactions were shown to proceed via a heterolytic mechanism however, the oxidations of related active methylene compounds (without the alcohol functionality) were determined to be free-radical processes. 

A high degree of stereoselectivity was achieved in reductive radical cyclizations with Coordination of the oxime function (e.g. 108) with samarium cation seems to play an important role, since the identical reaction with a tributyltin hydride/radical initiator system produces poor stereoselectivity (equation 79). ... 

A reductive amination/cyclization step was performed on the aldehyde 392 upon reaction with a variety of amines in the presence of sodium triacetoxyborohydride in THF/AcOH at room temperature to give the tetrahydropyr-ido[2,3 pyrituidine 393 (Equation 34) <2005BML1829>. 

Figure 4.11. Examples of redox-initiated radical reactions. Samarium diiodide reduction of the bromide gives a radical that cyclizes faster than the second reduction reaction. Manganese triacetate oxidation of the P-keto ester gives an enol radical that is not further oxidized by the manganese reagent. The IBX oxidizes anilides to the corresponding radicals. Hexamethylphosphoramide = HMPA and Tetrahydrofuran = THE.

The cross-coupling of alkynylzinc halides or fluorinated alkenylzinc halides with fluori-nated alkenyl iodides allows the preparation of a range of fluorinated dienes or enynes - Functionalized allylic boronic esters can be prepared by the cross-coupling of (dialkylbo-ryl)methylzinc iodide 428 with functionalized alkenyl iodides. The intramolecular reaction provides cyclized products, such as 429 (Scheme 109) ° °. In some cases, reduction reactions or halogen-zinc exchange reactions are observed. 

Glutamate is converted to proline by cyclization and reduction reactions. 

Irradiation of enamines (249) results in processes related to reduction and cyclization reactions with the participation of the enamine /3-carbon atom (82JOC482). A benzazepine derivative (250) was isolated as one of the products. Enamines (251) interact with aldehydes in a smooth reaction and give diazepines [84CPB3274 91KFZ(11)16]. Benzodiazepine derivatives can be obtained in a similar fashion (95KGS336). 

Synthetically useful routes to dibenzo[c,e J[l,2]dithiins are normally based on cyclizations of biphenyI-2,2 -disulfonyl chlorides. A method applied successfully to the parent compound reduces the precursor with zinc in acetic acid to generate the bis thiol, which is then gently oxidized to the dithiin using iron(II) chloride (66HC(21-2)952). An alternative one-step reductive cyclization, which has been applied to the preparation of the 2,9- and 3,8-dinitro derivatives, involves reduction of the appropriate bis sulfonyl chlorides with hydriodic acid in acetic acid (68MI22600). Yet another reductive cyclization uses sodium sulfite followed by acidification, and these conditions lead to dibenzo[c,e][1,2]dithiin 5,5-dioxide. The first step of the reaction is reduction to the disodium salt of biphenyl-2,2 -disulfinic acid which, on acidification, forms the anhydride, i.e. dibenzo[c,e][l,2]dithiin 5,5,6-trioxide. This is not isolated, but is reduced by the medium to the 5,5-dioxide (77JOC3265). Derivatives of dibenzo[c,e] [1,2]dithiin in oxidation states other than those mentioned here are obtainable by appropriate oxidation or reduction reactions (see Section 2.26.3.1.4). 

The more cationic halogen containing compounds produced other products. Cobalt bis-allyliodide produced cis-polybutadiene and the even more cationic chromium, produced cyclododecatriene. Only with the more cationic system which introduced trans-structures, was cyclization and reduction of the metal able to intercept the polymerization reaction. Cyclization was not possible in the less cationic cobalt which produces all cis-polybutadiene nor was the hydride transfer possible with the less anionic chromium tris-allyl compound. 

Intramolecular reductive amino cyclization.1 The key step in a synthesis of the ergot alkaloid aurantioclavine (3) from 3-formylindole (1) involves treatment of the nitro olefin 2 with amalgamated zinc in refluxing methanolic 2 N hydrochloric acid. Zn-HOAc, Fe-HOAc, SnCl2-HCl are not useful for this purpose. Cyclization is believed to involve an intermediate hydroxylamine, which can be isolated from short-term reactions. 

The highly stereoselective synthesis of 2,3-fr,ms--3-hydroxytetrahydropyran and 2,3-/ra r-3-hydroxyoxepane was achieved by the Sml2-induced reductive intramolecular cyclization from acyclic compounds having an aldehyde and a /3-alkoxyacrylate fragments <2002CL148>. Based on this reaction, new effective iterative syntheses of trans-fused 6,6,6-tricyclic, 6,7,6-tricyclic, and 6,7,7,6-tetracyclic ethers were developed <2002T1853>. 

Successful chemical and electrochemical synthesis of Pc from 1,3-D in aprotic solvents in comparison with those using PN shows that the highest influence of a solvent s nature on a reaction course takes place in the first stage of the process (1,3-D formation). For further reactions (cyclization and reduction of 1,3-D), a solvent s nature is not very important, as the results presented in Table 5.4 show. The formation of Pc from 1,3-D takes place in all the solvents used higher yields can be achieved by optimization of the process (variation of concentration of 1,3-D, use of electrosynthesis, and/or selection of the best solvent applied) [32]. 

Hydrostannylation This reaction with a tin hydride normally requires an initiator, usually AIBN but also B(C2H5)3 (14, 314). It can also be initiated with high intensity ultrasound, and such reactions show large rate acceleration (100-600 times) and take place even at temperatures of -50°. Sonication is also effective for radical reductions and cyclizations (last example). 

An alternative to reductive radical cyclization procedures is the use of group transfer methods. A novel group transfer cyclization reaction involving an organotellurium compound 47 has been described [95CC2515]. The bicyclic product 48 is formed as a 2 1 mixture of isomers at the terminus. 

An enamine intermediate has been proposed as being formed by hydride reduction of a transient iminium ion [14, 15]. The electrophilic capture of the enamine is possible by a Michael acceptor thus, reductive Michael cyclizations of enal enones such as 9 or 11 were described in many cases (intramolecular reactions) (Scheme 11.5) [16]. 

Reductive radical cyclization and tandem radical addition/cyclization reactions catalyzed by Ni(II) complexes, such as Ni(cyclam)(C104)2 98a, were studied starting in the 1990s by Ozaki s group [128]. The reaction conditions are applicable to alkyl and aryl halides bearing suitable positioned olefin units. Iodides and bromides can be used in some cases even aryl chlorides were successfully applied. The field was reviewed recently, and thus only more recent results are summarized here [19, 20]. 

Fig. 31 Reductive radical cyclization reactions of alkynyl halides catalyzed by Ni(I) complexes...

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