Carbenes cycloisomerization

Fiirstner and coworkers developed a new Pt- and Au-catalyzed cycloisomerization of hydroxylated enynes 6/4-141 to give the bicylo[3.1.0]hexanone skeleton 6/4-143, which is found in a large number of terpenes [317]. It can be assumed that, in the case of the Pt-catalysis, a platinum carbene 6/4-142 is formed, which triggers an irreversible 1,2-hydrogen shift. The complexity of the product/substrate relationship can be increased by using a mixture of an alkynal and an allyl silane in the presence of PtCl2 to give 6/4-143 directly, in 55 % yield (Scheme 6/4.36). 

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... 

The proposed mechanism of the above cycloisomerizations are depicted in Scheme 11.30. The oxidative coupling of a metal to an enyne yields a bicyclic metaUacyclopentene, which is a common intermediate. The reductive elimination and subsequent retro-[2+2] cycloaddition gave vinylcyclopentene derivatives, while the two patterns of P-elimination and subsequent reductive eUmination gave cychc 1,3- and 1,4-dienes, respectively. The existence of a carbene complex intermediate might explain the isomerization of the olefinic moiety. 

Gold(I)-catalysed cycloisomerizations of enynes (38) afford gold-carbene complexes (39) that have been trapped in an intramolecular fashion yielding highly strained tetracycles (40).38... 

Cycloisomerization or metathesis also occurs, which can be understood as the formation of cyclobutene 326 by reductive elimination of 321. The metathesis product 327 is formed by isomerization of 326. The metatheses involving metal-carbene complexes are discussed in Section 7.2.6. They are closely related, but somewhat different from the metathesis explained here. Balance between the ene and the metathesis reactions seems to be delicate. 

Up to this point Pd, Pt and Ru-catalysed enyne metatheses have been explained without involvement of metal-carbenes. However, carbenoid species seem to play a key role in these metatheses (or cycloarrangements) based on the following polycyclization involving cyclopropanation. Polycyclic ring systems are constructed by the cycloisomerization of dienynes catalysed by Ru, Pt, Rh, Ir and Re complexes... 

Silver salts or reagents have received much attention in preparative organic chemistry because they are useful catalysts for various transformations involving C-G and C-heteroatom bond formation.309 Especially, the silver(i)/ BINAP (2,2 -bis(diphenylphosphino)-l,T-binaphthalene) system is a very effective catalyst for a variety of enantio-selective reactions, including aldol, nitroso aldol, allylation, Mannich, and ene reactions. Moreover, silver salts are known to efficiently catalyze cycloisomerization and cycloaddition reactions of various unsaturated substrates. Recently, new directions in silver catalysis were opened by the development of unique silver complexes that catalyze aza-Diels-Alder reactions, as well as carbene insertions into C-H bonds. 

Pt(II) to the alkyne of the substrate likely triggers all these events. The cycloisomerization might undergo a metallacyclic intermediate that proceeds to eliminate /3-H. The formation of cyclopropanes is presumably succeeded via alkenyl platinum carbene followed by platina(IV)cyclobutane intermediates. The extension using formal metathesis of the enynes includes two transformations, the formation of 1,3-diene moieties and the stereoselective tetrasubstituted aUcene derivatives via O C allyl shift, both leading to diverse structural motifs and serving as the key step in the total synthesis of bioactive targets (Scheme 83). 

Asymmetric synthesis of nucleosides via molybdenum-catalyzed alkynol cycloisomerization coupled with stereoselective glycosylations of deoxyfuranose glycals and 3-amidofuranose glycals. Journal of the American Chemical Society, 118, 6648-6659 (b) McDonald, F.E. and Chatterjee, A.K. (1997) Group VI metal-promoted endo-azacyclizations via alkyne-derived metal vinylidene carbenes. Tetrahedron Letters, 38, 7687-7690 ... 

Shortly after the discovery of enyne metathesis, Trost began developing cycloisomerization reactions of enynes using Pd(ll) and Pt(ll) metallacyclic catalysts (429-433), which are mechanistically divergent from the metal-carbene reactions. The first of these metal catalyzed cycloisomerization reactions of 1,6-enynes appeared in 1985 (434). The reaction mechanism is proposed to involve initial enyne n complexation of the metal catalyst, which in this case is a cyclometalated Pd(II) cyclopentadiene, followed by oxidative cyclometala-tion of the enyne to form a tetradentate, putative Pd(IV) intermediate [Scheme 42(a)]. Subsequent reductive elimination of the cyclometalated catalyst releases a cyclobutene that rings opens to the 1,3-diene product. Although this scheme represents the fundamental mechanism for enyne metathesis and is useful in the synthesis of complex 1,3-cyclic dienes [Scheme 42(fe)], variations in the reaction pathway due to selective n complexation or alternative cyclobutene reactivity (e.g., isomerization, p-hydride elimination, path 2, Scheme 40) leads to variability in the reaction products. Strong evidence for intermediacy of cyclobutene species derives from the stereospecificity of the reaction. Alkene... 

Scheme 41. Examples of (a) tungsten and (i ) chromium Fischer carbene-mediated enyne cycloisomerization reactions.

Electrophilic Au(I) complexes or their halide AuX analogoues typically cyclize enynes (I, Scheme 58) (475) by a 5-exo-dig pathway to give a variety of cycloisomerization and addition derivatives. The mechanism is proposed to involve formation of a cyclopropyl gold-carbene intermediate... 

Scheme 59. l,8-Dien-3-yne substrate cycloisomerization and ring expansion via a cyclopiopyl gold-carbene intermediate. 

Another cycloisomerization pathway of 1,6-enynes involves intramolecular cyclopropanation of the alkene by the alkyne (Scheme 4-24). This reaction is favored for enynes bearing a cyclic olefin and probably proceeds by 6-encto-dig-cyclization, followed by proton loss and protodeauration of the gold carbene... 

Various other nucleophiles can be employed for the trapping of cyclopropyl gold carbenes formed by cycloisomerization of 1,6-enynes. The intermolecular hydroxycyclization or alkoxycyclization of 1,6-enynes in the presence of water or alcohols is also catalyzed by Pt(II) or Pd(II), but they proceed under milder conditions and more efficiently in the presence of cationic gold(I) catalysts. ... 

A related carbene formed in the coordination sphere of a gold(I) complex has been identified as a potential intermediate in the cycloisomerization of an alkynylindole/ The complex exhibits both carbocationic and a carbenic character. 

Cycloisomerization of 1,5-enynes with gold complexes containing highly electron-donating Ugands proceed via carbene-like intermediates to give a bicyclo-[3.1.0]hexenes (Scheme 127). ... 

A highly e fi o-selective gold- and silver-catalyzed cycloisomerization of 1,4-diynes has been developed (Wilckens et al. 2010). By employing electron-rich phosphines and A-heterocyclic carbenes as ligands, a number of 1,4-diynes could be cyclized in a desymmetrizing fashion to form dihydrodioxepines and enantiomeri-cally enriched tetrahydrooxazepines (Scheme 11.11). 

When 1,6-diene 46 was catalyzed by Grubbs carbene complex/trimethylsilyl vinyl ether or NiBr2(PPh3)2/Et2AlCl, exo-methylene cyclic compound 47 was obtained as the major product of the cycloisomerization (Scheme 27) (64,65). 

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