Alkynes cyclotrimerization with

A highly electron-deficient carbon-oxygen double bond can also participate in the co-cyclotrimerization with alkynes under the ruthenium catalysis. The cycloaddition of commercially available diethyl ketomalonate with the diynes 21 proceeded at 90 °C in the presence of 5-10 mol % Cp RuCl(cod). The expected fused 2ff-pyrans 27, however, underwent thermal electrocyclic ringopening to produce cyclopentene derivatives 28 (Eq. 14) [23]. 

In the 1990s, Zenneck and Mathey [33] described the use of a Fe(0) piano-stool-type complex. This approach was hampered by difficult catalyst preparation and poor chemoselectivity, leading to the pyridine products. In 2002, Ferr6 et al. [34] described the [2-I-2-I-2] cyclotrimerization with alkynes and a nitrile using stoichiometric quantities of CpFe(MeCN)3 to form pyridines. 

Transition metal-catalyzed intermolecular [2 + 2 + 2] cyclotrimerization of alkynes to benzene derivatives has been extensively studied. In this section, the focus is on the cyclo-trimerizations of the substrates bearing three independent unsaturated bond components. The key issue with this type of process usually involves the challenge of controlling regioselectivity [1—1]. However, 1,3,5-trisubstituted benzene 44 can be obtained as the sole product in good yield when 3-butyn-2-one 43 is used as the substrate for the cyclotrimerization catalyzed by Rh2(pfb)4 (pfb=perfluorobutyrate) in the presence of EtsSiH under a CO atmosphere (Eq. 11) [30]. 

An interesting appHcation of the rhodium-catalyzed cyclotrimerization of diynes with alkynes to the synthesis of C-acyl glycosides has been reported, wherein ethynylglycal 52 (Eq. 15), as well as diethynylglucose derivative 54 (Eq. 16), are employed to give the corresponding adducts 53 and 55, respectively [38]. 

Reactions involving the [4 + 1 + 1] principle, an example of which is shown in equation (136), are rather uncommon and of strictly limited utility [3 + 2 + 1] and [2 + 2 + 2] processes, on th,e other hand, are well known. Representative [3 + 2+1] three-bond formation processes are given in equations (137)—(141), from which it can be seen that the common situation is where ammonia, a substituted amine or formamide constitutes the one-atom fragment. Many [2 + 2 + 2] atom fragment syntheses are known and some are familiar reactions. Thus, the cobalt(I)-catalyzed condensation of nitriles and isocyanates with alkynes gives pyridines and 2-pyridones, often in excellent yield (e.g. equation 142), while the cyclotrimerizations of nitriles, imidates, isocyanates, etc., are well established procedures for the synthesis of 1,3,5-triazine derivatives (e.g. equation 143). Further representative examples are given in equations (144)-(147), and the reader is referred to the monograph chapters for full discussion of these and other [2 + 2 + 2] processes. Examination of the... 

This mechanism is supported by the transformation of preformed metallacyclo-pentadienes with alkynes,73,76-78 and labeling experiments79 that excluded the involvement of cyclobutadiene intermediates. It also accounts for the observation that terminal alkynes yield 1,2,4- (and 1,3,5-) trisubstituted benzene derivatives as the main product but not 1,2,3 derivatives. In contrast with this picture in cyclotrimerization with PdCl2-based catalysts, stepwise linear insertion of alkynes takes place without the involvement of palladacyclopentadiene.80... 

Okamoto and coworkers recently described the iron-catalyzed cyclotrimerization of alkynes utilizing a low-valent iron-diimine complex that was generated in situ upon reduction with zinc dust (Scheme 9.34) [92]. 

An analogous cleavage of a nickeladisilacyclopentene with alkyne is shown in entry 116. It has been pointed out (297) that these reactions show certain similarities to metal-catalyzed cyclotrimerization of alkynes or to cycloaddition of alkynes and substituted disilanes, postulated to involve Si-metal intermediates. 

Selective cyclotrimerization of alkynes with nitriles produced pentasubstituted pyridines (1) with little formation of benzenoid products (Scheme 1) <94CB(127)2535>. 

Co-Cyclotrimerizations of Alkynes with Carbon-Heteroatom Multiple Bonds... 

Numerous transition metal-mediated [2 + 2+2] cycloadditions have been utilized in the synthesis of pyridines . Selective cyclotrimerization of alkynes with nitriles leads to pentasubstituted pyridines 310 with minimal formation of benzenoid byproducts (Scheme 157) <20000L3131>. Different alkynes can be utilized in the same strategy if a sequential approach is used (Scheme 158) <2000JA4994>. 

The Pauson-Khand reaction (PKR) is among the most powerful transformations in terms of molecular complexity increment [1]. Only a few of other reactions like the Diels-Alder, or the cyclotrimerization of alkynes can compete with the PKR, which consists formally of a [2 + 2 + 1] cycloaddition in which a triple bond, a double bond and carbon monoxide form a cy-clopentenone [2-12], This constitutes one of the best ways to construct cyclopentenones, which upon further transformations can be converted into structures present in numerous natural products (Scheme 1). 

Particularly important advances have been made recently in the chemistry of M2(OR)6 compounds. Many examples of simple crosswise addition of a R C CR" molecule to M2(OR)6, in the presence of pyridine, have been observed. The products differ in the details of structure and composition depending on the nature of R, R, and R", and on whether M is Mo or W, but in each case there is a quasitetrahedral M2Q cluster in which an M=M bond (2.55 to 2.66 A in length) is present. These simple adducts will react further with alkynes to give products in which two or more alkyne molecules have been linked, as in (18-C-XXIII). Further reaction affords alkyne cyclotrimerization products (substituted benzenes). 

Cyclotrimerization of alkynes mediated by the cationic complex [(77-Cp)Ru(acetonitrile)3](PF6) was shown by the DFT methods to proceed via the ruthenacyclopentadiene intermediates in accord with experimental findings <2003JOM(682)204>. One illustration for the transformation of such an intermediate into the final product is illustrated... 

Reactions of [MoCl3(thf)3] with cyclic trithioethers C-S3 afforded the Mo complexes, [MoCl3(c-S3)] and [MoCl3(ttob)], and with neat tetrahydrothiophene (tht), mer-[MoCl3(tht)3] was formed. This latter complex was an active catalyst for the selective polymerization and cyclotrimerization of alkynes. 

The cyclotrimerization of alkynes to give benzene derivatives is perhaps the most general reaction of these compounds in the presence of transition metal complexes. Practically any mono- or di-substituted alkyne, in addition to acetylene itself, may be cyclotrimerized. In addition, cocycloadditions involving more than one different alkyne are possible with some degree of selectivity, and intramolecular versions of the reaction have seen sophisticated development. 

As is clear from the introductory discussion, most, if not all, of the d-block transition metals are expected to participate in reactions that are related to those discussed here. In addition to the Co-based methodology mentioned earlier, some related reactions of Pd and are known. Also related are the cyclization reactions of metal-carbene complexes containing Cr, Mo, W and other transition metals with alkynes and alkenes and a recently reported Nb- or Ta-promoted diyne-alkyne cyclization reaction, which appears to be closely related to a number of previously developed alkyne cyclotrimerization reactions, such as those catalyzed by Co. Investigations of reactions involving other transition metals may prove to be important especially from the viewpoint of developing asymmetric and catalytic procedures. 

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