Metal-Catalyzed Alkyne Activation

In 2010, Toste s group reported the first example of a highly enantioselective polyene cyclization reaction in which transition metal-promoted alkyne activation serves as the cyclization initiating event [34], The (MeO-DTBM-BIPHEP)gold(I)-catalyzed reaction offers an efficient method for the stereoselective synthesis of polycyclic compounds... 

The skeletal rearrangements are cycloisomerization processes which involve carbon-carbon bond cleavage. These reactions have witnessed a tremendous development in the last decade, and this chemistry has been recently reviewed.283 This section will be devoted to 7T-Lewis acid-catalyzed processes and will not deal, for instance, with genuine enyne metathesis processes involving carbene complex-catalyzed processes pioneered by Katz284 and intensely used nowadays with Ru-based catalysts.285 By the catalysis of 7r-Lewis acids, all these reactions generally start with a metal-promoted electrophilic activation of the alkyne moiety, a process well known for organoplatinum... 

Malacria and co-workers76 were the first to report the transition metal-catalyzed intramolecular cycloisomerization of allenynes in 1996. The cobalt-mediated process was presumed to proceed via a 7r-allyl intermediate (111, Scheme 22) following C-H activation. Alkyne insertion and reductive elimination give cross-conjugated triene 112 cobalt-catalyzed olefin isomerization of the Alder-ene product is presumed to be the mechanism by which 113 is formed. While exploring the cobalt(i)-catalyzed synthesis of steroidal skeletons, Malacria and co-workers77 observed the formation of Alder-ene product 115 from cis-114 (Equation (74)) in contrast, trans-114 underwent [2 + 2 + 2]-cyclization under identical conditions to form 116 (Equation (75)). 

The transition metal cross-couplings of allenes described here offer practical solutions for the modification of 1,2-dienes and access to the preparation of highly functionalized 1,3-dienes, alkynes and alkenes, which are often not easily accessible in a regio- and stereoselective manner by classical methods. Some of the prepared alkynes or functionalized allenes serve as important intermediates in syntheses of natural products, biologically active compounds, e.g. enynes and enyne-allenes, and new materials. It can be predicted that further synthetic efforts will surely be focused on new applications of allenes in transition metal-catalyzed cross-coupling reactions. 

The excellent ability of late transition metal complexes to activate alkynes to nucleophilic attack has made them effective catalysts in hydroamination reactions. The gold(l)-catalyzed cyclizations of trichloroacetimidates 438, derived from homopropargyl alcohols, furnished 2-(trichloromethyl)-5,6-dihydro-4f/-l,3-oxazines 439 under exceptionally mild conditions (Equation 48). This method was successfully applied to compounds possessing aliphatic and aromatic groups R. With R = Ph, cyclization resulted in formation of 439 with complete (Z)-stereoselectivity <2006OL3537>. 

To see whether water could be activated and added to Jt-systems other than alkynes, the metal-catalyzed hydrolysis of nitriles was studied [20]. For this purpose novel homodimeric and heterodimeric bis(acetylacetonato)ruthenium(ii) complexes bearing the 6-diphenylphosphino-N-pivaloyl-2-aminopyridine (10a) and 3-diphenylphosphinoisoquinolone (Ila) ligands were prepared. The molecular structures of these precatalyst were studied in solution and also in the solid state and revealed some unusual hydrogen-bonding patterns, in particular for the heterodimeric system in which the acetylacetonato ligand is involved (Scheme 2.7). 

The cyclopropanation of alkenes, alkynes, and aromatic compounds by carbenoids generated in the metal-catalyzed decomposition of diazo ketones has found widespread use as a method for carbon-carbon bond construction for many years, and intramolecular applications of these reactions have provided a useful cyclization strategy. Historically, copper metal, cuprous chloride, cupric sulfate, and other copper salts were used most commonly as catalysts for such reactions however, the superior catalytic activity of rhodium(ll) acetate dimer has recently become well-established.3 This commercially available rhodium salt exhibits high catalytic activity for the decomposition of diazo ketones even at very low catalyst substrate ratios (< 1%) and is less capricious than the old copper catalysts. We recommend the use of rhodium(ll) acetate dimer in preference to copper catalysts in all diazo ketone decomposition reactions. The present synthesis describes a typical cyclization procedure. 

The intramolecular Alder-ene reaction (enyne cydoisomerization reaction) with alkynes as the enophiles has found wide application compared with diene systems. The reason may be the ready chemo-differentiation between alkene and alkyne functionality and the more reactive alkyne moiety. Furthermore, the diene nature of the products will promote further applications such as Diels-Alder reactions in organic synthesis. Over the past two decades the transition metal-catalyzed Alder-ene cycloisomerization of l,n-enynes (typically n= 6, 7) has emerged as a very powerful method for constructing complicated carbo- or heterocydic frameworks. The transition metals for this transformation indude Pd, Pt, Co, Ru, Ni-Cr, and Rh. Lewis acid-promoted cydoisomerization of activated enynes has also been reported [11],... 

Considering the mechanistic rationales of the transition metal-catalyzed enyne cycloisomerization, different catalytic pathways have been proposed, depending on the reaction conditions and the choice of metal catalyst [3-5, 45], Complexation of the transition metal to alkene or alkyne moieties can activate one or both of them. Depending on the manner of formation of the intermediates, three major mechanisms have been proposed. The simultaneous coordination of both unsaturated bonds to the transition metal led to the formation of metallacydes, which is the most common pathway in transition metal-catalyzed cycloisomerization reactions. Hydrometalation of the alkyne led to the corresponding vinylmetal species, which reacts in turn with olefins via carbometalation. The last possible pathway involves the formation of a Jt-allyl complex which could further react with the alkyne moiety. The Jt-allyl complex could be formed either with a functional group at the allylic position or via direct C-H activation. Here the three major pathways will be discussed in a generalized form to illustrate the mechanisms (Scheme 8). 

Metal complexes enable one to employ molecules that are thermally unreactive toward cycloadditions by taking advantage of their ability to be activated through complexation. Most of the molecules activated by transition-metal complexes involve C-C unsaturated bonds such as alkynes, alkenes, 1,3-dienes, allenes, and cyclopropanes. In contrast, carbonyl functionalities such as aldehydes, ketones, esters, and imines seldom participate in transition-metal-catalyzed carbonylative cycloaddition reactions. Recently, such a transformation was reported via the use of ruthenium complexes. 

Starting from optically active nitriles, Botteghi and co-workers [32] have applied the cobalt-catalyzed reaction for the prepartion of optically active 2-substituted pyridines (eq. (8)). The chiral center is maintained during the alkyne-nitrile co-cyclization reaction. This reaction has recently been extended to the synthesis of bipyridyl compounds having optically active substituents [33] and provides an access to chiral ligands of potential interest in transition metal-catalyzed asymmetric synthesis. 

Parallel to the development of catalysts for olefin metathesis, the first alkyne metathesis catalysts were W and Mo metal oxides or carbonyls suspended on alumina or silica.65 The first homogeneous catalysts were developed by Mortreux and consisted of a mixture of Mo(CO)6 and substituted phenols.66 It was not until the work of Schrock and his collaborators, however, that a well-defined, isolable alkylidyne catalyst (38) was synthesized, characterized, and shown to catalyze alkyne metathesis.67 Later modifications on 38 included substituting the alkoxy groups with fluorinated analogs, and for the corresponding Mo alkylidynes (39), the fluorinated alkoxy groups are essential for catalytic activity.68... 

In 1954, Ziegler and coworkers [11,12] reported that traces of nickel salts dramatically alter the course of the growth reaction of ethylene with trialkylalanes, the Aufbau process. Instead of the low molecular weight polyethylene which was expected, the only product was butene. This observation culminated in Ziegler s discovery of transition metals that were highly effective in polymerizing ethylene, an accomplishment for which he later shared the Nobel Prize. It also opened the door to transition metal catalyzed hydroalumination reactions. In 1968, Eisch and Foxton showed that addition of nickel(II) salts increased the rate of the hydroalumination of alkynes by approximately 100-fold [13]. The active catalyst was believed to be a nickel(O) species. 

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