Cyclization reactions metal-catalysed

Oxidative cyclization is another type of oxidative addition without bond cleavage. Two molecules of ethylene undergo transition metal-catalysed addition. The intermolecular reaction is initiated by 7i-complexation of the two double bonds, followed by cyclization to form the metallacyclopentane 12. This is called oxidative cyclization. The oxidative cyclization of the a,co-diene 13 affords the metallacyclopentane 14, which undergoes further transformations. Similarly, the oxidative cyclization of the a,co-enyne 15 affords the metallacyclopentene 16. Formation of the five-membered ring 18 occurs stepwise (12, 14 and 16 likewise) and can be understood by the formation of the metallacyclopropene or metallacyclopropane 17. Then the insertion of alkyne or alkene to the three-membered ring 17 produces the metallacyclopentadiene or metallacyclopentane 18. 

Alkenes and alkynes coordinate to transition metals and undergo a variety of reactions, and are very important substrates for transition metal-catalysed reactions. Their reactions with halides, cyclization via carbene complexes, hydrogenation, and oxidative reactions with Pd(II) are treated in Sections 3.2, 8.2, 10.1 and 11.1, respectively. The many other reactions of alkenes and alkynes as main reactants are treated in this chapter. 

In terms of the yield and reaction rate, the Reformatskii reaction is a rather convenient route to biologically active 3-methylene-substituted 2-oxo-l,2-oxaphosphacyclanes 85, including those having a spiro-structure (Scheme 52) [116, 117]. Metal-catalysed formation of the P-C bond was also successfully used for the synthesis of similar phostones [118]. Thus, 3-methylene-1,2-oxaphosphacycla-nes 85 were formed in reasonable yields by palladium-catalysed intramolecular cyclization in a series of hydrophosphoryl compounds 86 (Scheme 52). 

In general, the main synthetic approaches to five- and six-membered 1,2-oxaphos-phacyclanes are based on intramolecular cyclizations in a series of co-halogenalkyl-, co-hydroxyalkyl-, and co-acetyloxyalkyl-substituted phosphorus compounds proceeding via different reaction mechanisms along with metal-catalysed transformations. As... 

The metal-catalysed cyclization of o-alkynyl anilines to indoles and o-alkynylphenols to benzofurans has been studied (Scheme 6.19). It is a useful method because the starting materials are readily available by Sonogashira reactions (Section 2.8). Cyclization followed by protonolysis of the t -intermediate 6.51 gives the heterocycle. As protonolysis regenerates a palladium(II) species, no added oxidant is required. In some cases, protonolysis is slow, and the reaction must be carried out in acidic conditions. ... 

In terms of synthetic planning, it must be noted that a transition-metal catalyst is not required for this cyclization. o-Alkynylamines can be cyclized to indoles under basic conditions, especially if the nitrogen atom has an electron-withdrawing substituent to lower the pKa. Just such a base-catalysed cyclization was employed in a synthesis of goniomitine (Scheme 6.20), after a Sonogashira reaction was employed to synthesize the substrate. Similarly, benzofurans are easily prepared by base catalysed cyclization as in a synthesis of Ailanthoidol (Scheme 2.115). The transition-metal catalysed cyclization is of particular importance when... 

This cycloaddition is thermally forbidden under the Woodward-Hoffmann rules, but can be achieved by the transition metal catalysed coupling of two dienes (Scheme 11.55). The transformation of butadiene into a variety of products, including cyclooctadiene 11.163, has been known for many years. The [4 + 4] cycloaddition reaction has been applied in an intramolecular fashion to form eight-membered rings (Scheme 11.56). In the presence of a source of nickel(O) and phosphine ligands, tetraene 11.164 cyclizes to the bicyclic product 11.165, mainly as the cu-isomer. The ratio of isomers is dependent on the phosphine. A stereogenic centre present in the tether between the two dienes can result in useful diastereoseleetivity, once again dependent on the phosphines. This chemistry has been used to synthesize asteriscanolide 11.166, which contains a substituted cyclooctane, by intramolecular cycloaddition of tetraene 11.168 to... 

Transition metal-catalysed methods for carbenoid insertion into C-H bonds remain well documented. The asymmetric intramolecular Cu(II)-catalysed C-H insertion reactions of (i) a-diazo-/ -keto esters and phosphonates and (ii) a-diazo sulfones have been described. One can note that the optimal reaction conditions have been found to be quite similar regardless of the nature of the carbenoid precursor the best conditions featured CUCI2 as Cu(II)-source, bis(oxazoline) (68) as chiral ligand and sodium tetrakis[3,5-bis(trifluoromethyl)phenyl] borate (i.e., NaBARF) as additive. Under the so-optimized reaction conditions, each of these carbenoid sources have been eonverted into five-membered cyclopentanone-based derivatives (69), whereas a-sulfonyl diazo esters (70) have led to six-membered cyclic compounds (71), thus featuring a distinct but well-known selectivity. In a related work, the asymmetric C-H insertion cyclization of (70) to (71) has also been achieved under Rh(II)-catalysis, using a combination of Rh2(5-pttl)4 (72) as chiral catalyst and menthyl ester as chiral auxiliary. As already mentioned in the previous section, allene-containing substrates (49) have been shown to undergo an intramolecular C-H insertion process under Rh(II)-catalysis. ... 

Transition metal complexes other than Co2(CO)8 catalyse the Pauson Khand reaction. The complex [RhCl(CO)2]2 catalyses the reaction of 224 [97], and Ru3(CO)12 [98] also catalyses these reactions at somewhat high temperatures. Highly enantioselective cyclization of 225 is catalysed by the chiral Ti(ebthi) complex to give 226 with 94% ee [99]. 

N-Tfa- and iV-Fmoc-a-amino ketones have been synthesized56 by reaction of some N -heterocycles or benzene with chiral AM Tfa- and Fmoc-a-aminoacyl)benzotriazoles [e.g. (49)] in the presence of aluminium trichloride. Full preservation of chirality was reported. Aromatic side-chains in some of the (a-amineacyl)benzotriazole compounds gave a competitive intramolecular cyclization, again with retention of chirality [e.g. (49) to (50)]. A full report57 on the intramolecular acylation of aromatics with Meldrum s acid derivatives catalysed by metal trifluoromethanesulfonates under mild reaction conditions has appeared [e.g. (51) to (52)]. The method tolerates many functional groups and was extended to the synthesis of 1-tetralones, 1-benzosuberones and donepezil (53). 

The thermal cyclization of ketones onto alkynes, the Conia-ene reaction, can proceed thermally but only at inconveniently high temperatures.39 Transition metals can catalyse it at lower temperatures but they require enolate generation, strong acid or photochemical activation. In the presence of phosphaneAu1 complexes, however, the reaction proceeds at ambient temperature under neutral conditions. For example, the following ketoester was converted into the cyclic product in 94% yield in 15 min in the... 

Scheme 9 Santonin (41) was converted to the derivative (99), whose conversion to alcohol (100) by metal hydride reduction and Mitsunobu reaction. Diol (102), prepared from (100), on acid catalysed cyclization and followed by subjection to Mitsunobu reaction, gave (104), which was converted to ketone (106), whose transformation to homoallylic alcohol (108), was achieved by standard organic reactions. Phenylselenylation afforded (110), which was finally converted to phytuberin.

The enantioselective spiro ring construction is an important issue because many natural compounds have chiral spiro centers [103,104]. Pd catalyses of Spiro cyclizations have been reported by asymmetric intramolecular Mizoroki-Heck reactions [105,106]. In spite of a similar potential, transition metal-catalyzed ene-type carbocyclization has never been applied to asymmetric spiro cyclizations [107-110]. 

Reactions with aikynes may aiso result in the formation of cyclized products. Thus a ruthenium-catalysed reaction with aromatic amides has been used to give isoquinoline derivatives. On the basis of values of the kinetic isotope effect, A h/ d> proposed that the rate-determining step is a concerted acetate-assisted metalation-deprotonation process to yield the intermediate (30), followed by aikyne insertion and ring closure. The reaction of arylketones with alkynes may yield indenols when catalysed by rhodium cyclopentadienyl in the presence of silver and copper salts. The reaction proceeds regioselectively, so that reaction of acetophenone with 1-phenyl-1-propene... 

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