Skeletal reorganizations

The general features of this elegant and efficient synthesis are illustrated, in retrosynthetic format, in Scheme 4. Asteltoxin s structure presents several options for retrosynthetic simplification. Disassembly of asteltoxin in the manner illustrated in Scheme 4 furnishes intermediates 2-4. In the synthetic direction, attack on the aldehyde carbonyl in 2 by anion 3 (or its synthetic equivalent) would be expected to afford a secondary alcohol. After acid-catalyzed skeletal reorganization, the aldehydic function that terminates the doubly unsaturated side chain could then serve as the electrophile for an intermolecular aldol condensation with a-pyrone 4. Subsequent dehydration of the aldol adduct would then afford asteltoxin (1). 

The elaboration of the polyunsaturated side chain of asteltoxin requires a stereoselective coupling of aldehyde 2 with a suitable synthetic equivalent for the anion of 4-formyl-1,3-butadiene (see intermediate 3 in Scheme 4). Acid-induced skeletal reorganization of the aldehyde addition product, followed by an intermolecular... 

Sanui T, Inayoshi A, Noda M, et al. DOCK2 regulates Rac activation and cyto-skeletal reorganization through interaction with ELMOl. Blood 2003 102(8) 2948-2950. 

There is another mechanistic variation to circumvent the direct cleavage process 11- 12. The isomerization 11- 13 does not necessarily have to involve a skeletal reorganization. For example, it can be envisaged that a specific hydrogen transfer occurs onto a suitable acceptor function Y, 24- 25 (5). In this way a reactive radical site is created which induces the dissociation step (elimination of X ) by... 

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. 

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. 

PVA as, 25 615-617 corrugator-applied, 13 19 Skeletal bending modes, 14 236 Skeletal reorganization mechanism, 26 954 Skeleton, 3 723... 

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). 

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. 

Skeletal reorganization is a useful tool for the synthesis of complicated natural products. Fiirstner achieved formal total syntheses of antibiotics metacycloprodigiosin and streptorubin B by platinum-catalyzed skeletal reorganization... 

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). ... 

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. 

Platinum complexes (continued) with aryls, thallium adducts, 3, 399 with bis(alkynyl), NLO properties, 12, 125 with bisalkynyl copper complexes, 2, 182-186 with bis(3,5-dichloro-2,4,6-trifluorophenyl), 8, 483 and C-F bond activation, 1, 743 in C-H bond alkenylations, 10, 225 in C-H bond electrophilic activation studies, 1, 707 with chromium, 5, 312 with copper, 2, 168 cyclometallated, for OLEDs, 12, 145 in diyne carbometallations, 10, 351-352 in ene-yne metathesis, 11, 273 in enyne skeletal reorganization, 11, 289 heteronuclear Pt isocyanides, 8, 431 inside metallodendrimers, 12, 400 kinetic studies, 1, 531 on metallodendrimer surfaces, 12, 391 mononuclear Pt(II) isocyanides, 8, 428 mononuclear Pt(0) isocyanides, 8, 424 overview, 8, 405-444 d -cP oxidative addition, PHIP, 1, 436 polynuclear Pt isocyanides, 8, 431 polynuclear Pt(0) isocyanides, 8, 425 Pt(I) isocyanides, 8, 425 Pt(IV) isocyanides, 8, 430... 

The trichothecene framework 114 was constructed by interesting Pd-catalysed skeletal reorganization via pinacolone rearrangement of the allylic lactone 111. The exo-7r-allylpalladium complex 112 is attacked intramolecularly by a carbon bond (pinacolone rearrangement) to give 113 [60]. 

The addition of aryl halides and divinyl or enyne carbinols to give tri- or tetra-substituted alkenes is considered to involve skeletal reorganization (Scheme 89) of an intermediate cyclopropanol.132 The ability to suppress /3-hydride elimination of organopalladium intermediates is critical to the success of these processes. 

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. 

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