Skeletal reorganization reaction

Enyne metathesis is unique and interesting in synthetic organic chemistry. Since it is difficult to control intermolecular enyne metathesis, this reaction is used as intramolecular enyne metathesis. There are two types of enyne metathesis one is caused by [2+2] cycloaddition of a multiple bond and transition metal carbene complex, and the other is an oxidative cyclization reaction caused by low-valent transition metals. In these cases, the alkyli-dene part migrates from alkene to alkyne carbon. Thus, this reaction is called an alkylidene migration reaction or a skeletal reorganization reaction. Many cyclized products having a diene moiety were obtained using intramolecular enyne metathesis. Very recently, intermolecular enyne metathesis has been developed between alkyne and ethylene as novel diene synthesis. 

Presumably, these skeletal reorganization reactions start by coordination of a metal ion to an alkyne part in 78 to allow an alkene part to attack the resulting electrophilic alkyne carbon coordinated by the metal. However, the reaction mechanism remains yet to be clarified, and it is thought that each reaction mechanism differs depending on the metal used. 

Trost succeeded in formal total synthesis of roseophilin. Macrocyclic compound 118 is synthesized from enyne 117 by platinum-catalyzed skeletal reorganization reaction and is converted into 119, which is further converted into pyrrole derivative 120 (Scheme 43). ... 

By use of Ru-based carbenes such as [Ru]-Ia, II, III, various carbo- and heterocycles can be synthesized from the corresponding enyne precursors. The metathesis is carried out not only by ring-closing enyne metathesis but also by dienyne metathesis, cross enyne metathesis, and ring-opening enyne metathesis.In this section, the synthetic applications of enyne metathesis reactions, including skeletal reorganization reactions and hetero-enyne metathesis, to natural products and related compounds are described. 

Fiirstner et al. succeeded in formal total syntheses of the antibiotics streptorubin B 279 and metacycloprodigiosin 280 by platinum-catalyzed skeletal reorganization reactions (Scheme 24.68). These antibiotics were isolated from Streptomyces spectabilis and Streptomyces coelicolor, respectively. The use of PtCl2 (5mol%) brought about formal metathesis reactions between the electron-... 

Trost and Doherty applied the Pt-catalyzed skeletal reorganization reaction of enyne 281 to the construction of bicyclic compound 282 for the formal total synthesis of roseophilin 285, which was isolated from Streptomyces... 

Fiirstner et al. achieved the formal total syntheses of the antibiotics metacyclo-prodigiosin and streptorubin B by a platinum-catalyzed skeletal reorganization reaction (Scheme 6.27) [33]. The key step leading to the meta-bridged pyrrole core structures consisted of a formal metathesis reaction of electron-deficient... 

The elusive diazoalkenes 6 and 14 are unlikely to react with methanol as their basicity should be comparable to that of diphenyldiazomethane. However, since the formation of diazonium ions cannot be rigorously excluded, the protonation of vinylcarbenes was to be confirmed with non-nitrogenous precursors. Vinyl-carbenes are presumedly involved in photorearrangements of cyclopropenes.21 In an attempt to trap the intermediate(s), 30 was irradiated in methanol. The ethers 32 and 35 (60 40) were obtained,22 pointing to the intervention of the al-lylic cation 34 (Scheme 10). Protonation of the vinylcarbene 31 is a likely route to 34. However, 34 could also arise from protonation of photoexcited 30, by way of the cyclopropyl cation 33. The photosolvolysis of alkenes is a well-known reaction which proceeds according to Markovnikov s rule and is, occasionally, associated with skeletal reorganizations.23 Therefore, cyclopropenes are not the substrates of choice for demonstrating the protonation of vinylcarbenes. 

Trost and Tanoury found an interesting skeletal reorganization of enynes using a palladium catalyst.In this reaction, the second product is derived from a metathesis reaction (Equation (5)). It was speculated that the reaction would proceed by oxidative cyclization of enynes with the palladium complex followed by reductive elimination and then ring opening. To confirm this reaction mechanism, they obtained a compound having a cyclobutene ring, which was considered to be formed by the reductive elimination (Equation (6)). 

The skeletal reorganization is found by Trost to proceed by a platinum complex, but the reaction course is suggested to differ from the one previously mentioned (Equation (7)). " ... 

PtCl2 constitutes an efficient and practical catalyst for skeletal rearrangement reaction of enynes. This includes a formal enyne metathesis reaction delivering 1,3-dienes. Skeletal reorganization of enyne 75a having a carbon chain in... 

Iridium complex [IrCKCOls] also catalyzes skeletal reorganization of enyne 78d to 79d (Scheme 32). In contrast, enyne 78e having a methyl group on an alkyne terminal fails to give any products under the same reaction. Use of... 

Very recently, the same group reported skeletal reorganization of enynes to 1-vinylcycloalkene by GaCls-Reaction of 78f, for example, proceeds in toluene at 0 °C and is completed within 1 h to give 79f. It is interesting that highly strained cyclobutene derivative 82 is obtained from 1,7-enyne 78g (Scheme 33). 

An even more complex series of bond formation and cleavage attends the construction of a secodine precursor for tabersonine [95], The initial tetracyclic intermediate provides two 3-carbon links between the two nitrogen atoms and therefore reaction pathways for skeletal reorganization. 

The term intramolecular enyne metathesis describes two types of processes. One involves a [2+2] cycloaddition of a multiple bond and a transition-metal carbene complex and the other is an oxidative cyclization catalyzed by low-valent transition-metal complexes, for example, Pt, Pd and Ru. The latter reaction is also called a skeletal reorganization. Both processes lead to similar products (Eq. 84). 

Ruthenium-catalyzed skeletal reorganization involving organosilicon compounds have been reported by Chatani et al. [ 140] (Eq. 85). The reaction provides an efficient method for converting enynes to vinylcycloalkenes. 

Ring-protonated alkylcyclopropanes, well-known in solution , were suggested to explain the most unusual behaviour of heptyl ions. Extensive C- and D-labelling as well as a computer simulation and the analysis of CA data indicate that the major fragmentation reactions of CvHj s ions, generated via loss of I from 1-heptyl iodide, are preceded by extensive skeletal reorganization which via cyclopropane-like structures (140, 142, 144) eventually isomerize to tertiary carbocations (145 and 146, Scheme 23 where only the carbon skeleton is shown). The latter serve as actual precursors for the loss of CsH. ... 

The elimination of OH and H2 (20) from ortho and peri substituted alkoxy aldehydes, ketones or quinones is of diagnostic value for the location of functional groups113 114 The reaction sequence is restricted to systems containing such a substitution pattern. Investigations of 2H and lsO labelled model compounds establish the origin of neutral species (OH and H2) without clarifying the details of the complex skeletal reorganization. From the results it can only be concluded that the formation of stable oxonium ions, e. g., 105, is of importance. 

Wittig and related reactions. 2-Alkenyl-2-methoxycyclopropyl ylides afford methylenecyclopentenes on treatment with BuLi, due to skeletal reorganization of the initial products. ... 

Skeletal reorganization occurs in radical intermediates, primarily via hydrogen atom shifts observed that are probably hydrogen abstraction reactions. An example is the Barton reaction, 2 jf, which an alkoxy radical... 

In this section are discussed a number of thermal isomerization reactions of substances having one or more carbon-carbon double bonds in which skeletal reorganizations occur without cleavage of bonds to substituents which may be bonded to the carbon skeleton. 

Transition metal-catalyzed carbocyclizations of 1,6-enynes A [7-11] such as cycloisomerization [12-18], metathesis [19-30], skeletal reorganization [31-34], and ene reactions [35] are useful synthetic methods leading to five-membered rings (Scheme 4). Transition metal-catalyzed carbocyclizations of... 

---