Mechanism, metal catalyzed cycloadditions

Despite the great synthetic utihty of diazocarbonyl compounds in the generation of carbonyl ylide intermediates, definitive mechanistic studies on the metal-catalyzed cycloaddition of carbonyl yhdes are scarce. Among the various metal catalysts, dirhodium(II) catalysts are the most effective and versatile for diazo decomposition. Because of the rapid catalytic tmnovers of these reactions, structural information about the intermediates is difficult to obtain. A reasonable mechanism can be rationahzed on the basis of product distribution, and especially on the basis of enantioselective outcome of various carbonyl yhde reactions [55-63]. 

Treating diene-yne derivatives 50 with ferrate 40 does not lead to the expected ene-allenes, instead the [4 + 2]-cycloaddition products 51 are obtained in moderate yields (eq. 1 in Scheme 11). As metal-catalyzed Diels-Alder-reactions of unactivated aUcynes and dienophiles are assumed to proceed via metaUacyclic intermediates, this supports the mechanism for the Alder-ene-reaction discussed before. 

Cobalt, as its CpCo(CO)2 complex, has proven to be especially suited to catalyze [2 + 2 + 2] cycloadditions of two alkyne units with an alkyne or alkene. These cobalt-mediated [2 + 2 + 2] cycloaddition reactions have been studied in great detail by Vollhardt337. The generally accepted mechanism for these cobalt mediated cycloadditions, and similar transition metal mediated cycloadditions in general, has been depicted in equation 166. Consecutive co-ordination of two triple bonds to CpCo(CO)2 with concomitant extrusion of two molecules of carbon monoxide leads to intermediates 578 and 579 via monoalkyne complex 577. These react with another multiple bond to form intermediate 580. The conversion of 578 to 580 is said to be kinetically favored over that of 579 to 580. Because intermediates like 580 have never been isolated, it is still unclear whether the next step is a Diels-Alder reaction to form the final product or an insertion to form 581. The exact circumstances might determine which pathway is followed. 

The cycloaddition reaction of dipoles has been known since the late eighteenth century however, before Huisgeris introduction of the concept of a 1,3-dipole, these reactions were considered to proceed via a diradical mechanism [16]. One of the earhest examples of metal-catalyzed 1,3-dipole formation involved the controlled decomposition of an a-dia-... 

A combined system formed from Co(acac)3, 4 equiv of diethylalu-minum chloride, and chiral diphosphines such as (S,S)-CHIRAPHOS or (/ )-PROPHOS catalyzes homo-Diels-Alder reaction of norbomadiene and terminal acetylenes to give the adducts in reasonable ee (Scheme 109). Use of NORPHOS in the reaction of phenylacetylene affords the cycloadduct in 98.4% ee (268). It has been postulated that the structure of the active metal species involves noibomadiene, acetylene, and the chelating phosphine. The catalyzed cycloaddition may proceed by a metallacycle mechanism (269) rather than via simple [2+2 + 2] pericyclic transition state. 

In consideration of conceivable strategies for the more direct construction of these derivatives, nitriles can be regarded as simple starting materials with which the 3+2 cycloaddition of acylcarbenes would, in a formal sense, provide the desired oxazoles. Oxazoles, in fact, have previously been obtained by the reaction of diazocarbonyl compounds with nitriles through the use of boron trifluoride etherate as a Lewis acid promoter. Other methods for attaining oxazoles involve thermal, photochemical, or metal-catalyzed conditions.12 Several recent studies have indicated that many types of rhodium-catalyzed reactions of diazocarbonyl compounds proceed via formation of electrophilic rhodium carbene complexes as key intermediates rather than free carbenes or other types of reactive intermediates.13 If this postulate holds for the reactions described here, then the mechanism outlined in Scheme 2 may be proposed, in which the carbene complex 3 and the adduct 4 are formed as intermediates.14... 

Reduction of alkylidene malonates (60) in MeOH in an undivided cell using alkali metal halides as supporting electrolytes results in the unusual formation of 3,4-disubsti-tuted 1,1,2,2-cyclobutanetetracarboxylates, 61 [141]. Cyclobutane formation requires 4-7 F and is not a radical anion-catalyzed cycloaddition. The process was explained by the mechanism in Scheme 11, where the cyclization takes place by chemical oxidation of the... 

Low-valent transition metal catalyzed versions of [2 + 2] cycloadditions. especially with nickel catalysts, were recognized early as useful alternatives to thermal and photochemical methods12-15. The observation of transition metal catalysis, active in [2 + 2]-cycloaddition reactions, originally caused considerable discussion of the mechanism as an inversion of symmetry rules, effected by the transition metal, may be assumed. Thus, it was suggested that, in the presence of the metal catalyst, a forbidden reaction becomes allowed 16,17. This interpretation, however, could not be verified for the overall process, since experimental investigations revealed a stepwise mechanism with metallacycle intermediates18-23. 

An important factor which could influence asymmetric induction would be that cycloaddition is faster than catalyst decomplexation from the ylide. Although the precise mechanism remains unclear, the high levels of enantios-election in intermolecular cycloadditions with dipolarophiles provide definite support for the intermediacy of a chiral rhodium(II)-associated carbonyl ylide involved in the cycloaddition step. These examples indicate that metal-catalyzed dipole formation followed by cycloaddition has the potential to be a powerful method for asymmetric synthesis. 

Generally proposed mechanisms of the transition metal-catalyzed [2+2+2] cycloaddition of alkynes are shown in Schemes 19.1 and 19.2. Two alkynes react with the transition metal complex to generate metallacyclopentadiene A. The subsequent [4+2] cycloaddition of A with the alkyne affords metallabicyclo[2.2.0]heptadiene B. Reductive elimination affords the desired benzene (Schemes 21.1). Alternatively, insertion of the alkyne into A leading to metallacycloheptatriene C followed by reductive elimination also affords the desired benzene (Schemes 19.1). The mechanism via the intermediates A and B is confirmed in the CpCo(I)-phosphine complex-catalyzed [2+2+2] cycloaddition of alkynes by the theoretical calculation [5]. 

SCHEME 21.1 Mechanism of transition metal-catalyzed [2+2+2] cycloaddition (1). 

When two alkyl groups are coordinated to the same metal atom with a cis relationship, the complex is expected to readily release the alkyl coupling product. Although a variety of mechanisms may be conceived for the metal-catalyzed [2 -I- 2] cycloaddition of olefins (reviews Mango and Schachtschnei-der, 1971 Kricka and Ledwith, 1974), definite evidence for the intervention of a metallocyclic intermediate has been provided. On reacting [Ir(l,5-cyclo-octadiene)Cl]2 with excess norbomadiene in acetone, an insoluble complex is... 

Scheme 5 The mechanism of transition metal-catalyzed [5-1-2] cycloaddition...

Taking advantage of the rich chemistry of transition-metal-catalyzed cycloisomerization of 1,6-enynes, the electron-rich, conformationally blocked cyclohepta-1,3, 5-triene has been envisioned as a 6-% nucleophilic component [59]. Thus, cycloisomerization of l-(pent-4-ynyl)cyclohepta-l,3,5-trienes in the presence of catalytic amounts of platinum(II) chloride led to a formal intramolecular [64-2] cycloaddition in good to excellent yields [60]. These reactions are conducted at room temperature in toluene as the solvent. A heteroatom in the tether between the unsaturated subunits is tolerated, although in these cases other catalytic pathways were also observed. A mechanism involving cationic intermediates resulting from the nucleophilic attack of the triene on the metal-alkyne moiety has been proposed (Scheme 8.38). The occurrence of ionic intermediates was supported with... 

Synthesis of Substituted Heterocycles Transition-metal-mediated or transition-metal-catalyzed co-cycloaddition of two alkynes and one nitrile is one of the simplest synthetic pathways to construct pyridine framework. However, there is a critical problem in selectivity in the intermolecular coupling of two different alkynes and a nitrile resulting from the reaction mechanism via metalacyclopentadi-ene [17]. For example, in Co-mediated pyridine formation, cobaltacyclopentadiene 37 was first prepared from two different alkynes by sequential addition because aza-cobaltacyclopentadiene could not be formed via selective coupling of one alkyne and a nitrile. A mixture of two pyridine regioisomers was obtained in the final step due to the existence of two possible orientations of the nitrile toward cobaltacyclopentadiene intermediate 37 [Scheme 11.15, Eq. (1)] [17b,c]. To control the... 

---