Metathesis, alkene reactivity

Metathesis is inherently flexible. As a result, this transformation allows, inter alia, for a rapid chemistry-driven evaluation of structure/activity profiles and qualifies for applications in combinatorial and diversity oriented synthesis this is particularly true when combined with suitable post-metathesis transformations exploiting diverse alkene reactivity. 

These carbene (or alkylidene) complexes are used for various transformations. Known reactions of these complexes are (a) alkene metathesis, (b) alkene cyclopropanation, (c) carbonyl alkenation, (d) insertion into C-H, N-H and O-H bonds, (e) ylide formation and (f) dimerization. The reactivity of these complexes can be tuned by varying the metal, oxidation state or ligands. Nowadays carbene complexes with cumulated double bonds have also been synthesized and investigated [45-49] as well as carbene cluster compounds, which will not be discussed here [50]. 

The possibility of being involved in olefin metathesis is one of the most important properties of Fischer carbene complexes. [2+2] Cycloaddition between the electron-rich alkene 11 and the carbene complex 12 leads to the intermediate metallacyclobutane 13, which undergoes [2+2] cycloreversion to give a new carbene complex 15 and a new alkene 14 [19]. The (methoxy)phenylcar-benetungsten complex is less reactive in this mode than the corresponding chromium and molybdenum analogs (Scheme 3). 

Similar reactivity is observed in the cyclization of enynes in the presence of the yttrium-based catalyst 70 and a silane reductant [53,54]. The 1,6- and 1,7-enynes 90 and 91 provide -E-alkylidene-cyclopentancs 92 and -cyclohexanes 93 in very good yield (Eq. 15, Scheme 20) [55]. These transformations likely proceed by syn hydrometallation of the 7r-basic alkyne, followed by insertion of the alkene and a-bond metathesis. The reaction of 1,6-enynes tolerated... 

The gas-phase reaction of cationic zirconocene species, ZrMeCp2, with alkenes and alkynes was reported to involve two major reaction sequences, which are the migratory insertion of these unsaturated hydrocarbons into the Zr-Me bond (Eq. 3) and the activation of the C-H bond via er-bonds metathesis rather than /J-hydrogen shift/alkene elimination (Eq. 4) [130,131]. The insertion in the gas-phase closely parallels the solution chemistry of Zr(R)Cp2 and other isoelec-tronic complexes. Thus, the results derived from calculations based on this gas-phase reactivity should be correlated directly to the solution reactivity (vide infra). 

The success of the cross-metathesis reactions involving styrene and acrylonitrile led to an investigation into the reactivity of other Ji-substituted terminal alkenes [27]. Vinylboranes, enones, dienes, enynes and a,p-unsaturated esters were tested, but all of these substrates failed to undergo the desired cross-metathesis reaction using the molybdenum catalyst. 

Attacking the problem of cross-metathesis selectivity from a different angle, Crowe and co-workers explored the reactivity of a more nucleophilic partner for the Ji-substituted alkenes. They chose to use allyltrimethylsilane since they proposed that the CH2SiMe3 substituent should have a negligible effect on alkyli-dene stability, but enhance the nucleophilicity of the alkene via the silicon P-ef-fect (Fig. 1). 

Use of a symmetrical acyclic alkene limits the possible metathesis products to the desired diene (for example 45) and products formed from polymerisation of the cyclic substrate. Competing ROMP was suppressed in these reactions by using dilute conditions and a tenfold excess of hex-3-ene. By adding the cyclic substrate slowly to a solution of the catalyst and ris-hex-3-ene (which was significantly more reactive than the trans isomer), less than two equivalents of the acyclic alkene were used without causing a significant drop in the cross-metathesis yield. 

Carbenes are both reactive intermediates and ligands in catalysis. They occur as intermediates in the alkene metathesis reaction (Chapter 16) and the cyclopropanation of alkenes. As intermediates they carry hydrogen and carbon substituents and belong therefore to the class of Schrock carbenes. As ligands they contain nitrogen substituents and are clearly Fischer carbenes. They have received a great deal of attention in the last decade as ligands in catalytic metal complexes [58], but the structural motive was already explored in the early seventies [59],... 

There are no mechanistic details known from intermediates of copper, like we have seen in the studies on metathesis, where both metal alkylidene complexes and metallacyclobutanes that are active catalysts have been isolated and characterised. The copper catalyst must fulfil two roles, first it must decompose the diazo compound in the carbene and dinitrogen and secondly it must transfer the carbene fragment to an alkene. Copper carbene species, if involved, must be rather unstable, but yet in view of the enantioselective effect of the ligands on copper, clearly the carbene fragment must be coordinated to copper. It is generally believed that the copper carbene complex is rather a copper carbenoid complex, as the highly reactive species has reactivities very similar to free carbenes. It has not the character of a metal-alkylidene complex that we have encountered on the left-hand-side of the periodic table in metathesis (Chapter 16). Carbene-copper species have been observed in situ (in a neutral copper species containing an iminophosphanamide as the anion), but they are still very rare [9],... 

The order of reactivity of these three catalysts towards alkenes (but also towards oxygen) is 1 > 3 > 2. As illustrated by the examples in Table 3.18, these catalysts tolerate a broad spectrum of functional groups. Highly substituted and donor- or acceptor-substituted olefins can also be suitable substrates for RCM. It is indeed surprising that acceptor-substituted alkenes can be metathesized. As discussed in Section 3.2.2.3 such electron-poor alkenes can also be cyclopropanated by nucleophilic carbene complexes [34,678] or even quench metathesis reactions [34]. This seems, however, not to be true for catalysts 1 or 2. 

Species (A) and (B) constitute the main class of unsaturated carbenes and play important roles as reactive intermediates due to the very electron-deficient carbon Cl [1]. Once they are coordinated with an electron-rich transition metal, metal vinylidene (C) and allenylidene (D) complexes are formed (Scheme 4.1). Since the first example of mononuclear vinylidene complexes was reported by King and Saran in 1972 [2] and isolated and structurally characterized by Ibers and Kirchner in 1974 [3], transition metal vinylidene and allenylidene complexes have attracted considerable interest because of their role in carbon-heteroatom and carbon-carbon bond-forming reactions as well as alkene and enyne metathesis [4]. Over the last three decades, many reviews [4—18] have been contributed on various aspects of the chemistry of metal vinylidene and allenylidene complexes. A number of theoretical studies have also been carried out [19-43]. However, a review of the theoretical aspects of the metal vinylidene and allenylidene complexes is very limited [44]. This chapter will cover theoretical aspects of metal vinylidene and allenylidene complexes. The following aspects vdll be reviewed ... 

Metal allenylidene complexes (M=C=C=CR2) are organometallic species having a double bond betv een a metal and a carbon, such as metal carbenes (M=CR2), metal vinylidenes (M=C=CR2), and other metal cumulenylidenes like M=C=C= C=CR2 [1]. These metal-carbon double bonds are reactive enough to be employed for many organic transformations, both catalytically and stoichiometrically [1, 2]. Especially, the metathesis of alkenes via metal carbenes may be one ofthe most useful reactions in the field of recent organic synthesis [3], vhile metal vinylidenes are also revealed to be the important species in many organic syntheses such as alkyne polymerization and cycloaromatization [4, 5]. 

A detailed study showed that the alkyne-alkene metathesis was proceeding cleanly, but that the product 10 was then decomposed by the Ru catalyst. Use of the less reactive first generation Grubbs catalyst 9 gave clean conversion of 8 to 10. 

The organic reactivity of the alkylidyne complexes has been extensively studied especially with regard to alkene and alkyne metathesis reactions.353,356... 

The makeup of Mo-based complexes, represented by 1 [3], offers an attractive opportunity for the design, synthesis, and development of effective chiral metathesis catalysts. This claim is based on several factors 1) Mo-based catalysts such as 1 possess a modular structure [4] involving imido and alkoxide moieties that do not disassociate from the metal center in the course of the catalytic cycle. Any structural alteration of these ligands may thus lead to a notable effect on the reaction outcome and could be employed to control selectivity and reactivity. 2) Alkoxide moieties offer an excellent opportunity for incorporation of chirality within the catalyst structure through installment of non-racemic tethered chiral bis(hydroxy) ligands. 3) Mo-based complexes provide appreciable levels of activity and may be utilized to prepare highly substituted alkenes. 

There thenfollowed reports by Katz [13] and Grubbs [14] and their co-workers on studies that aimed to simplify and confirm the analysis. The key remaining issue was whether a modified pairwise mechanism, in which another alkene can coordinate to the metal and equilibrate with the product prior to product displacement, would also explain the appearance of the anomalous cross-over products early in the reaction evolution. However, a statistical kinetic analysis showed that for a 1 1 mixture of equally reactive alkenes, the kinetic ratio of cross-metathesis should be 1 1.6 1 for the pairwise mechanism and 1 2 1 for the Chauvin mechanism. Any equilibration (substrate or product) would, of course, cause an approach towards a statistical distribution (1 2 1) and thus allow no distinction between the mechanisms. 

At present, Mo, W, Re and Ru complexes are known to catalyse alkene metathesis [7]. This unique reaction, catalysed by transition metal complexes, is impossible to achieve by other means. Later, based on studies of the reactivities of Fischer-type carbene complexes, it was discovered that carbene complexes are the intermediates in alkene metatheses. WClg reacts with EtAlCl2 to afford the diethyltungsten complex 3 by transmetallation, and subsequent elimination of a-hydrogen generates ethane and the carbene complex 4 which is the active catalyst. 

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