Carbocyclizations metallacycle

Evans and co-workers simultaneously developed of the rhodium-catalyzed [4-+2 + 2] car-bocychzation reaction through the identification of a novel mode of reactivity for the five-membered metallacycle intermediate [14, 37]. Evans proposed that 1,3 dienes should be amenable to addition to this intermediate, which would provide a new reaction pathway. The tethered enyne 80 (Scheme 12.9), was expected to afford the metallacycle I, which, upon sequential incorporation of a butadiene and reductive ehmination, would afford the desired 5,8-fused product 81. Additionally it was rationahzed that this transformation should be highly diastereoselective, as outlined in Scheme 12.10. Treatment of the heteroatom-tethered enyne I under standard carbocyclization (Pauson-... 

Metallacycles have been claimed to play pivotal roles in many transition metal-mediated multi-component coupling reactions [1]. For example, [2 -i- 2 -i- 2] alkyne cyclo-trimerization leading to benzenes - the Reppe reaction - has been considered to proceed via metallacyclopentadiene and elusive metallacycloheptatriene intermediates ("common mechanism ), while metallacyclopentenes have been proposed as intermediates for the [2 -i- 2 -i- 1] cyclo-coupling reactions of an alkyne, an alkene, and CO leading to a cyclopentenone (the Pauson-Khand reaction). A metallacyclic compound - which is defined here as a carbocyclic system with one atom replaced by a transition metal element - can be generally formed by oxidative cyclization of two unsaturated molecules with a low-valent transition metal fragment [2-4]. Alter-... 

The titanacyclopentadiene derivatives are converted into cyclopentadienols (Scheme 124) as an example for organic transformations of metallacyclic complexes into carbocyclic substances.254... 

Of the two possible isomers where R = Me, only the transmetallacycle is detectable by NMR. Other alkenes fail to give metallacycles by this method. The reaction also fails with the Nb analog of HI. The metallacycles, IV, are unstable at 25°C and are sensitive to air and water. If 1,7-octadiene is used in place of ethylene in Eq. (e), then metallacycle V, stable below 100°C, is obtained . The fused carbocycle thus aids stability. 

Although these novel Rh-catalyzed [2+2+2+1] cycloadditions of endiynes 525 with CO gave similar products to those from CO-SiCaT reactions, the mechanism of the reaction is totally different. The CO-SiCaT reaction is a stepwise process of carbocyclizations, whereas the Rh-catalyzed [2+2+2+1] cycloaddition proceeds via a series of metallacycles (Figure 2-20). ... 

In addition to the syntheses of carbocycles in Scheme 3-38, oxygen-, silicon-, and aluminum-containing heterocycles have also been prepared by [2+2+1] cycloadditions. An interesting tetrahydrofuran synthesis involves stoichiometric metallacycle formation by oxidative cyclization of Ni(0) with two equivalents of norbomadiene, followed by oxygen atom insertion with N2O (Scheme 3-39). 

The relative ease of the cyclization step from A to C may also be linked to the nucleophilic or coordinative ability of the heteroatom bound to the metal. The reaction of 7 with diphenylacetylene (Ph2C2) leads to the seven-membered derivatives 68 and 69 after prior isolation of the monoinsertion product 24, treatment with a silver salt, followed by the usual thermolytic conditions. This is another rare example of an intramolecular formation of a C-S bond within the coordination sphere of a transition metal and a novel, albeit limited to one alkyne, route to the rare family of dibenzo[bd] thiepins. With the closely related 8, which differs from 7 only by the tertiary amine unit in the metallacyclic framework instead of a thioether function, a carbocyclic product 71 is obtained (see under carbocycle reactions, next section). The formation of the seven-membered S-heterocycles is attributed to the good coordinative ability of the thioether group in 7. The S-atom remains close to the vinylic carbon function before the cyclization. With the poorly coordinating, readily displaced amine function in 8, the N-atom is detached from the metal and ultimately affords a spirocyclic product (see Scheme 18). 

C-C bond-forming reactions do not, however, always involve spirocyclic intermediates. The cyclopentadienyl product 111 is obtained during the depalladation of 110, derived from a thermally induced 1,3-H shift of its isomer 114. Here, PPhj plays a role similar to that of pyridine or maleic anhydride, in that it displaces the quinoline unit bound to palladium and, hence destabilizes the metallacyclic unit. The carbocyclic product 111 is assumedly formed as a result of an intramolecular C-H activation of the ri -bound olefin unit assisted by the proximity of the... 

Metallacycles are also featured in Chapters 2 and 3 of this volume. Cobalt- and nickel-based metallacycles are key cataljrtic intermediates in Transition-Metal-Catalyzed Cycloaddition Reactions of Bicy-clo[2.2.1]heptadienes by Professor Mark Lautens and Dr. William Tam of the University of Toronto (Chapter 2). The high sttain energy of norbomadiene makes possible many of the interesting processes covered in this informative chapter. It is followed by a comprehensive review of the State of the Art in Selective Hetero- and Carbocyclic Synthesis Mediated by Cyclometallated Complexes ... 

Scheme 97) illustrates the proposed mechanism of this novel process. This reaction is believed to proceed through a series of metallacycles. Thus, it is clearly different from that of the CO-SiCaT reaction, which is a stepwise process involving sequential carbocyclizations. The proposed mechanism includes (i) selective coordination of the diyne moiety of enediyne 216 to the active Rh catalyst species, forming metallacycle N-I [2-1-2-l-M]) (ii) insertion of the olefin moiety of 216 into the Rh-C bond forms the fused 5-7-5 tricyclic rhodacycle N-II ([2-I-2-I-2-I-M]) (iii) coordination of CO to the Rh metal followed by migratory insertion of CO into the Rh—C bond gives 5-8-5 rhodacycle N-III or N-IV ([2-I-2-I-2-I-1-I-M]) and (iv)... 

Mazumder S, Shang D, Negru DE, Baik M-H, Evans PA (2012) Stereoselective rhodium-catalyzed [3-I-2-I-1] carbocyclization of alkenylidenecyclopropanes with carbon monoxide theoretical evidence for a trimethylenemethane metallacycle intermediate. J Am Chem Soc 134(51) 20569-20572. doi 10.1021/ja305467x... 

VCPs have served as valuable five-carbon components in various cycloaddition reactions. Usually, they form six-membered metallacycles upon oxidative cycliza-tion with transition metals. Then, migratory insertion of unsaturated molecules, followed by reductive elimination, furnishes the carbocycles. In particular, intermolecular [5-1-2] annulation of VCPs with alkynes, alkenes, and allenes has been studied extensively (Scheme 2.39) [57]. In addition, VCP-cyclopentene rearrangement has been well documented [56 ]. 

Similarly to cyclopropanes, four-membered carbocyclic compounds undergo oxidative addition to low-valent transition metals to form five-membered metallacycles. Rhodium(I) inserts into C-C bonds next to the carbonyl group of ketones to form a rhodacycloalkanone species [49]. The C-C bond of cyclobutanone was cleaved, even at room temperature, by oxidative addition to a rhodium(I) complex having a PBP pincer ligand [50]. In the case of cyclobutanone 70, catalytic decarbonylation was possible and afforded the alkene 71 and cyclopropane 72 (Scheme 3.40). 

Carbocycles are important compounds in natural products and functional materials. The traditional preparative methods for cyclic compounds include the Diels-Alder addition reaction, and cyclization mediated by Lewis acid and base. With the aid of metallacycles, carbocycles are often prepared in high yields with high selectivity from different components (Scheme 1). Among many metallacycles, zirconacycles and titanacycles with Cp ligands have been most widely used in stoichiometric reactions to prepare carbocycles. 

There have been several excellent reviews and books dealing with preparation methods of zirconacycles and titanacycles, especially on the formation of 3- and 5-membered zirconacycles [ 1-5]. Therefore, this paper will not describe details of preparation of 3- and 5-membered zirconacycles, which are the most popular metallacycles of zirconocene and titanocene. In order for readers to find appropriate references, a brief introduction into preparative methods of these metallacycles is given. Applications of zirconacycles and titanacycles in the construction of useful carbocyclic compounds from multi-components are summarized. 

Construction of carbocycles from metallacycles is attractive. Theoretically, for example, reaction of a five-membered metallacycle with a one-carbon unit may afford a five-membered carbocycle. A six-membered carbocycle may be formed from insertion of a two-carbon unit into a five-membered metallacycle. However, in many cases, skeletal rearrangement of in situ generated metallacycles takes place, thus making prediction of structures of products very difficult. Accordingly, in this section, we focus on the carbocycles formed, regardless of the starting metallacycles. 

Formation of three-membered carbocycles from the reaction of three-mem-bered metallacycles (or metallocene-alkyne or -alkene complexes) with a one-carbon unit can be considered to be the most straightforward way (Scheme 2). However, such a preparative route has not been reported. 

Conversion of the five-membered metallacycles into five-membered carbocycles, where the metal is eventually replaced with one carbon atom, is an attractive method for the construction of five-membered carbocycles (Eq. 38). In fact, such transformation is very popular using five-membered metallacycles of titanocenes and zirconocenes [1-5]. 

In conclusion, five-membered metallacycles of titanocene and zirconocene are convenient starting materials for the construction of five-membered car-bocyclic compounds. The formation of five-membered carbocycles can be accomplished by addition reactions (or insertion reactions) of a variety of electrophiles, such as CO, RCN, RNC, bis(trichloromethyl)carbonate, allenyl carbenoids, halogencarbenoids, aldehyde, acyl chlorides, propynoates, and iodopropenoatesthe to the five-membered metallacycles. 

Insertion of a ttvo-carbon unit into a five-membered metallacycle may afford formation of a six-membered carbocycle (Eq. 60), such as a benzene derivative via a formal [2+2+2] aromatization of three alkynes. Similarly, insertion of a C-X unit such as a nitrile into a five-membered metallacycle may afford formation of a six-membered heterocycle, such as a pyridine derivative (Eq. 60). In recent years, Takahashi laboratory and other laboratories have developed a number of synthetically useful methods for six-membered cyclic compounds by taking advantage of five-membered metallacycles of zirconocenes and ti-tanocenes [1-5]. 

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