Other reductive cyclization

In this analysis, the activation barrier for both C1-C6 and C1-C5 cyclizations of enediyne radical-anions can be described as the avoided crossing between the out-of-plane and in-plane MOs (configurations). One-electron reduction populates the out-of-plane LUMO of the enediyne moiety. At the TS (the crossing), the electron is transferred between the orthogonal re-systems to the new (in-plane) LUMO. This effect leads to the accelerated cyclization of radical-anions of benzannelated enediynes, a large sensitivity of this reaction to re-conjugative effects of remote substituents and the fact that this selectivity is inverse compared to that of the Bergman cyclization. Similar electronic effects should apply to the other reductive cyclization reactions that were mentioned in the introduction. 

With the knowledge promulgated by Baeyer, Jackson, Weerman, Reissert, Heller, Beilstein, Ruggli, and others, reductive cyclization routes to indole have been explored. 

An oxidative cyclization, (151) -> (152), with azodicarboxylate (78CC764) is balanced by the synthesis of 5-deazaalloxazines from aryl bis(6-aminouracilyl)methanes, which involves azodicarboxylate in an intermediate electrophilic capacity (153 -> 154) (79CPB2507). Other methods involve reductive cyclizations (72AP751). 

Other zinc reductions have been used extensively. Zinc dust in aqueous ammonium chloride is a standard reagent for the reductive cyclization of nitro esters to hydroxamic acids. These reactions are usually carried out at low temperatures (0°-10°) to avoid further reduction. Despite the fact that good yields can often be obtained, these reductions are highly capricious, depending on the quality of the zinc (impurities seem to improve the reaction) and other unknown factors. 

Similar to the Fisher indole synthesis, reductive cyclization of nitro aromatics offers a powerful means of forming indoles. Reductive cyclization of ortho, 2 -dinitrostyrenes has occurred in many ways, by TiCl3, NaBH4-Pd/C, H2-Pcl/C, and other reductive methods.89 Corey and coworkers have used the Borchardt modification (Fe-AcOFI, sihca gel, toluene at reflux for the reductive cyclization of o-ji-dinitrostyrenes) to prepare 6,7-dimethoxyindole (Eq. 10.65) in a total synthesis of aspidophytine (see Schemes 3.3 and 3.4 in Section 3.2.l).89d... 

Few other examples of such reaction sequences have been described to date. Oh has reported the palladium-catalyzed reductive cyclizations of 1,6-enynes in the presence of formic acid or triethylsilane via an alkylpalladium intermediate and its application to organic synthesis. Palladium complexes also catalyze the conversion of a range of enynes to cyclic 6,7-unsaturated carboxylic acids in the presence of CO.260... 

The use of organomagnesium reagents as terminal reductants in zirconocene-catalyzed diene reductive cyclization permits derivatization of the resulting bis(magnesiomethyl)cycloalkanes. However, the use of other stoichiometric reductants is likely to afford catalytic systems that exhibit complementary selectivity profiles. Molander reports the... 

The current mechanistic understanding of these reductive cyclization processes is largely conjecture. Stepwise oxidative addition, migratory insertion, and reductive elimination (see Scheme 26) is a widely proposed mechanism. However, other mechanisms - such as initial cyclometallation - are to afford a rhodacyclopentadiene followed by either oxidative addition to a rhodium(v) intermediate or (perhaps more likely) bond metathesis with an additional molecule of silane (Scheme 28). 

The previous chapter covered radical cation cyclization reactions that were a consequence of single-electron oxidation. In the following section, radical anion cyclization reactions arising from single-electron reduction will be discussed. In contrast to the well documented cyclization reactions via carbon-centered free radicals [3, 4], the use of radical anions has received limited attention. There are only a few examples in the literature of intramolecular reductive cyclization reactions via radical anions other than ketyl. Photochemi-cally, electrochemically or chemically generated ketyl radical anions tethered to a multiple bond at a suitable distance, have been recognized as a promising entry for the formation of carbon-carbon bonds. 

The literature contains several references to reductive cyclizations producing cyclic hydroxamic acids like those described above, though not in solid-phase chemistry.43-47 We showed that this reaction competes well with lactam formation. The relative extent of these two reaction pathways is highly dependent on the presence and the nature of other heteroatoms and substituents around the ring system as well as on the conditions used to effect the reduction. 

Another interesting modification of the method is the reductive cyclization of ketodiester oximes. This modification considerably extends the scope of the method and makes available other 1-azabi-cycloalkanes besides pyrrolizidines.42... 

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). 

Despite the demonstration of reductive cyclization of tetrabromopentaerythritol 8 to spiropentane almost a century ago14, the formation of methylenecyclobutane and other side products (equation 4) decreases the preparative importance of the method. 

Reductive coupling of carbonyls to alkenes Titanium(IV) chloride-Zinc, 310 of carbonyls to pinacols Titanium(III) chloride, 302 Titanium(IV) chloride-Zinc, 310 of other substrates Samarium(II) iodide, 270 Reductive cyclization 2-(Phenylseleno)acrylonitrile, 244 Tributylgermane, 313 Tributyltin hydride, 316 Triphenyltin hydride, 335 Trityl perchlorate, 339 Reductive hydrolysis (see Hydrolysis) Reductive silylation Chlorotrimethylsilane-Zinc, 82... 

In their prominent synthesis of brevetoxin B, Nicolaou et al. have investigated, among some other methods for construction of oxepine ring system, the reductive cyclization of keto alcohol 37 with triethylsilane and trimethylsilyl triflate giving oxepane 38 (Equation 12) <1995JA1173>. 

The unusual ability of DMP+ to promote the formation of 1 e" products, prompted attempts to use this catalyst for transformations other than pinacolization. The examples chosen were aimed at 1 e reductive intramolecular cyclizations. Shono and co-workers 88) have reported such cyclizations at graphite and Sn cathodes. Their experiments were carried at a constant current in concentrated solutions of (C2H5)4N+ electrolytes. The substrates used should have, in principle, been electroinactive within the potential window . It was therefore feasible to assume the intermediacy of (C2H5)4N-metal and it seemed that DMP+(Hg5) might be a more efficient and predictable catalyst for reductive cyclization. The study was fruitful. Shono-type cyclizations were achieved at Hg cathodes with DMP+ as the catalyst. Unlike at... 

To examine whether TAA+ cations other than DMP+ can catalyze intramolecular reductive cyclizations, the reduction of <59 was performed with 0.005 M (C2H5)4NBF4 in solution. Like DMP+, (C2HS)4N+ had a catalytic effect, 69 could be reduced at —2.80 V(SCE) and the cyclic alcohol 70 was obtained in high yield (94%). However, (C2H5)4N+ was less efficient and 6 F mol-1 were consumed for completion, while the DMP+ mediated reduction of 69 was complete after transfer of 2 F mol-1. 

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