Cyclization metalation

When platinum is alloyed with iridium (on an a-alumina support), which is a C5 cyclizing metal, the C5 cyelization selectivity of alloys containing 30-70% iridium remains nearly the same (about 0.15) and falls between that of platinum (about 0.6) and that of iridium (0.025). The aromatization (and... 

Related Cyclization/Metallation Processes 11.11.9.1 Stannylative Cyclization... 

Sequential transition-metal-catalyzed processes are dominated by palladium-17], rhodium- [8], and ruthenium- [9] catalyzed sequences. With respect to Fogg s and de Santos classification, only cyclizing metal-catalyzed one-pot processes [1] in the sense of auto and assisted tandem catalysis will be discussed and highlighted in this overview. 

Synthesis by high-dilution techniques requires slow admixture of reagents ( 8-24 hrs) or very large volumes of solvents 100 1/mmol). Fast reactions can also be carried out in suitable flow cells (J.L. Dye, 1973). High dilution conditions have been used in the dilactam formation from l,8-diamino-3,6-dioxaoctane and 3,6-dioxaoctanedioyl dichloride in benzene. The amide groups were reduced with lithium aluminum hydride, and a second cyclization with the same dichloride was then carried out. The new bicyclic compound was reduced with diborane. This ligand envelops metal ions completely and is therefore called a cryptand (B. Dietrich, 1969). 

The direct connection of rings A and D at C l cannot be achieved by enamine or sul> fide couplings. This reaction has been carried out in almost quantitative yield by electrocyclic reactions of A/D Secocorrinoid metal complexes and constitutes a magnificent application of the Woodward-Hoffmann rules. First an antarafacial hydrogen shift from C-19 to C-1 is induced by light (sigmatropic 18-electron rearrangement), and second, a conrotatory thermally allowed cyclization of the mesoionic 16 rc-electron intermediate occurs. Only the A -trans-isomer is formed (A. Eschenmoser, 1974 A. Pfaltz, 1977). 

Pd-cataly2ed reactions of butadiene are different from those catalyzed by other transition metal complexes. Unlike Ni(0) catalysts, neither the well known cyclodimerization nor cyclotrimerization to form COD or CDT[1,2] takes place with Pd(0) catalysts. Pd(0) complexes catalyze two important reactions of conjugated dienes[3,4]. The first type is linear dimerization. The most characteristic and useful reaction of butadiene catalyzed by Pd(0) is dimerization with incorporation of nucleophiles. The bis-rr-allylpalladium complex 3 is believed to be an intermediate of 1,3,7-octatriene (7j and telomers 5 and 6[5,6]. The complex 3 is the resonance form of 2,5-divinylpalladacyclopentane (1) and pallada-3,7-cyclononadiene (2) formed by the oxidative cyclization of butadiene. The second reaction characteristic of Pd is the co-cyclization of butadiene with C = 0 bonds of aldehydes[7-9] and CO jlO] and C = N bonds of Schiff bases[ll] and isocyanate[12] to form the six-membered heterocyclic compounds 9 with two vinyl groups. The cyclization is explained by the insertion of these unsaturated bonds into the complex 1 to generate 8 and its reductive elimination to give 9. 

TRANSITION METAL-CATALYSED CYCLIZATION OF A/-ALLYL-AND /V-PROPARGYL ANILINES... 

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). 

ISlew Synthetic Approaches. There have been a number of efforts to prepare quinolines by routes quite different from the traditional methods. In one, the cyclization of 3-ariiino-3-phenyl-2-alkerLiniines (18) using alkah metals leads to modest yields of various 4-arylaminoqurnolines (54). Because this stmcture is found in many natural products and few syntheses of it exist, the method merits further investigation. 

Complexation with metals has been observed with a variety of pyridopyridazinones, whilst electrophilic attack at nitrogen is involved in cyclizations to a variety of azolo and azino fused tricyclic systems, e.g. (65CPB586, 7UOC3812). 

The converse situation in which ring closure is initiated by the attack of a carbon-based radical on the heteroatom has been employed only infrequently (Scheme 18c) (66JA4096). The example in Scheme 18d begins with an intramolecular carbene attack on sulfur followed by rearrangement (75BCJ1490). The formation of pyrrolidines by intramolecular attack of an amino radical on a carbon-carbon double bond is exemplified in Scheme 19. In the third example, where cyclization is catalyzed by a metal ion (Ti, Cu, Fe, Co " ), the stereospecificity of the reaction depends upon the choice of metal ion. 

Sebacoin has been prepared only by cyclization of methyl or ethyl sebacate with sodimn metal. ... 

Macrocycles have been prepared by formation of macrocyclic imines as well as by using variations of the Williamson ether synthesis ". Typically, a diamine or dialdehyde is treated with its counterpart to yield the Schiff s base. The saturated macrocycle may then be obtained by simple reduction, using sodium borohydride, for example. The cyclization may be metal-ion templated. In the special case of the all-nitrogen macrd-cycle, 15, the condensation of diamine with glyoxal shown in Eq. (4.14), was unsuccess-ful ... 

The first polyphosphino maeroeyeles designed speeifieally for use as transition metal binders were reported in 1977 in back-to-baek eommunications by Rosen and Kyba and their eoworkers. The maeroeyeles reported in these papers were quite similar in some respeets, but the synthetic approaches were markedly different. DelDonno and Rosen began with bis-phosphinate 18. Treatment of the latter with Vitride reducing agent and phosphinate 19, led to the tris-phosphine,20. Formation of the nickel (II) complex of 20 followed by double alkylation (cyclization) and then removal of Ni by treatment of the complex with cyanide, led to 21 as illustrated in Eq. (6.15). The overall yield for this sequence is about 10%. 

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. 

A modification of the K-R reaction was introduced by Mozingo. This method involved reacting an o-hydroxyacetophenone with an ester in the presence of metallic sodium to form a 1,3-diketone. Treatment of the diketone with an acid then delivered the chromone via an intramolecular cyclization reaction. This method was applied to the preparation of 2-ethylchromone (21). 0-hydroxyarylketone 22 was allowed to react with ethyl propionate (23) in the presence of sodium metal.The resulting sodium enolate was then quenched with acetic acid to deliver the 1,3-diketone 24. Upon heating 24 in glacial acetic acid and hydrochloric acid, 2-ethylchromone (21) was delivered in 70-75% overall yield. 

The salt 55 (R = H) did not cyclize on reduction with metal hydrides, but instead yielded the tryptamine derivative 58 (R = H) as the sole... 

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