Alkylidene formation

Cyclitols do not form alkylidene derivatives with the same ease as acyclic carbohydrates. However, the technique of Dangschat and Fischer, wherein zinc chloride catalysis is used, enables the formation of isopropylidene derivatives. They made brilliant use of this reaction in their elucidation of the structures of shikimic acid, quinic acid, conduritol, and mj/o-inositol (see above). The structures of the naturally occurring methyl ethers, pinitol and quebrachitol, were determined with the aid of this reaction (7, ISa, b), L-Inositol and cpi-inositol can be converted to triisopropylidene derivatives (7). This requires acetonation of trans hydroxyl groups. A chair conformation of the ring does allow vicinal trans hydroxyl groups in the equatorial plane to approach one another closely (7). 

Griffin and Nelson 106a) prepared a mono- and a dimethyl ether of m /o-inositol by the action of dimethyl sulfate and alkali. These were characterized as their crystalline acetates. Partial ethyl ethers were prepared similarly. Griffin and Nelson s monomethyl ether is apparently DL-bornesi-tol 119) (p. 274), which was also obtained by methylation of 1,3,4,5,6-penta-O-acetyl-mi/o-inositol 119). Because an acyl migration occurred during this methylation, the structure of the methyl ether is not established. McGowan 120) obtained the completely methylated compound by use of the methylation technique of West and Holden 121). A by-product of the reaction was a pentamethyl ether, which was later crystallized 122). 

There is only one instance in the literature of the preparation of a di-cyclitol ether. This was obtained by Prunier 100) by heating d-quercitol at 235-250°. A compound, m.p. 228-230°, and having the composition C12H22O9, sublimed. The residual sirup contained a small amount of substance (quercitan) which may be an internal ether. 

The cyclitols can form complexes with metals similar to those of the glycitols. The formation of an insoluble reaction product with basic lead acetate is a means of removing m /o-inositol almost quantitatively from solution 123). 

Inososes apparently exist in the enediol form in alkaline solution 91 y 124) they readily reduce 2,6-dichlorophenol-indophenol (the ascorbic acid reagent). Inososes cannot be acetylated under alkaline conditions, such as obtain with the conventional pyridine - acetic anhydride reagent, because aromatization occurs. Esters of inososes are likewise aromatized when heated with pyridine or sodium acetate 56), The deoxynitroinositols of Grosheintz and Fischer are converted to diacetyl-5-nitroresorcinol by pyridine and acetic anhydride 33), Attempts to convert cyclitols to cyclo-hexenetetrols (e.g., conduritol) by ordinary procedures of dehydration also result in the introduction of three double bonds. 

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A Mechanism for Alkylidene Formation. There is no unambiguous example of free-carbene capture by a metal substrate, and the mild reaction conditions used in the generation of these carbene complexes from diazoalkanes suggests that such a mechanism is highly unlikely here. Transition metal diazoalkane complexes, then, are almost certainly implicated as intermediates in these reactions. 

The same authors have demonstrated that 1,3-diynes behave in predictable yet distinctive manners compared to simple enynes under electrophilic transition metal-mediated reaction conditions. This characteristic behaviour of 1,3-diynes is presumably caused by the slightly electron-withdrawing nature of the alkynyl substituent, which not only renders preferentially the formation of 5-exotype alkylidenes but also allows for the subsequent [l,3]-metallotropic shift. Several salient features of reactions with this functionality include the following (a) an acetate is more reactive than the tethered alkene as an initiator, generating [l,2]-acetate migrated alkylidene intermediate, whereas an alkene is a better terminator than an acetate/bromide to generate the cyclopropane moiety (b) allene products are not formed at all under current reaction conditions (c) 5-exo/6-endo-type alkylidene formation depends on the heteroatom substituent in the tether (d) facile metallotropic [1,3]-shift of the intermediate alkylidenes occurred whenever possible. 

The catalytic desymmetrization shown in Scheme 5 involves a meso-tetraene substrate optically pure unsaturated siloxane 23 is obtained in >99% ee and 76% yield [16], The unreacted siloxy ether moiety is removed to deliver optically pure 24. Mo-alkylidenes derived from both enantiotopic terminal alkenes in 22 are likely formed. Since metal-alkylidene formation is reversible, the major product arises from the rapid RCM of the matched segment of the tetraene. If any of the mismatched RCM takes place, a subsequent and more facile matched RCM leads to the formation of the meso-bicyclized product. Such a byproduct is absent from the unpurified mixture containing 23, indicating the exceptionally high degree of stereodifferentiation induced by the chiral Mo complex. As before, catalyst 4a is not effective in promoting ARCM of 22. 

Reaction with Pi azoalkanes y-Alkylidene Formation. The react ioF f-diazoaTkanii-v7rth-Tr1msiTTonm an area of... 

The principle resonance contributions to the bonding in (H)3M(=CH2) were studied theoretically using a multi-reference wave function.19 The thermochemistry of Ta-alkylidene formation was examined, revealing a very large Ta=C bond enthalpy.20... 

A more recent example involving a-elimination is shown in equation 10.12. Here, Ag(I) is used to induce alkylidene formation by first oxidizing Ti to a (f1 state, which is followed by a-elimination and then RE of alkane. Similar chemistry occurs with vanadium and niobium complexes.31... 

The mechanism of alkylidene formation and thus chain initiation, in systems that contain no alkyl ligands either on the metal or cocatalyst still remains unknown. 

With the exocyclic alkylidene at C-13 properly in place, the elaboration of the l,5-diyn-3-ene moiety can now be addressed. Cleavage of both acetate and trimethylsilyl functions in 86 with basic methanol, followed by triethylsilylation of the newly formed tertiary hydroxyl group, efficiently affords alkyne 25 (86 % overall yield). This substance was regarded as a viable candidate for a Pd-catalyzed coupling reaction.12 Indeed, treatment of 25 with (Z)-chloroenyne 26 in the presence of a catalytic amount of Pd(PPh3)4 and Cu1 results in the formation of enediyne 24 in 91 % yield. 

Analogous results are obtained in the pyrolysis of 3-alkylidene-2,2,4,4-tetramethylene-thietane dioxides256 (244), 3-hydroxy and 3-keto thietane dioxides (245)191, and 1,3-dithietane dioxides and tetroxides (184b and 7b)192. The extrusion of both CO and S02 and the two S02 moieties in 245b-d and 7b, respectively, to give ethylene, the formation of... 

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]. 

While diene metathesis or diyne metathesis are driven by the loss of a (volatile) alkene or alkyne by-product, enyne metathesis (Fig. 2) cannot benefit from this contributing feature to the AS term of the reaction, since the event is entirely atom economic. Instead, the reaction is driven by the formation of conjugated dienes, which ensures that once these dienes have been formed, the process is no longer a reversible one. Enyne metathesis can also be considered as an alkylidene migration reaction, because the alkylidene unit migrates from the alkene part to one of the alkyne carbons. The mechanism of enyne metathesis is not well described, as two possible complexation sites (alkene or alkyne) exist for the ruthenium carbene, leading to different reaction pathways, and the situation is further complicated when the reaction is conducted under an atmosphere of ethylene. Despite its enormous potential to form mul-... 

The reactivity of a remarkable electronically unsaturated tantalum methyli-dene complex, [p-MeCgH4C(NSiMe3)2]2Ta( = CH2)CH3, has been investigated. Electrophilic addition and olefination reactions of the Ta = CH2 functionality were reported. The alkylidene complex participates in group-transfer reactions not observed in sterically similar but electronically saturated analogs. Reactions with substrates containing unsaturated C-X (X = C, N, O) bonds yield [Ta] = X compounds and vinylated organic products. Scheme 117 shows the reaction with pyridine N-oxide, which leads to formation of a tantalum 0x0 complex. ... 

A pair of reactions of 1,4-dihydropyridines with electron-accepting alkenes (Scheme 31) shows experimental evidence for the mechanistic spectrum between the pseudoexcitation and transfer bands. Acrylonitrile undergoes an ene reaction [143] (Scheme 31a). This is a reaction in the pseudoexcitation band. A stronger acceptor, alkylidene- and arylmethylydenemalonitriles are reduced [144] (Scheme 31b). This is a reaction in the transfer band, where a hydride equivalent shifts without bond formation between the ti bonds of the donors and acceptors. 

The cycloaddition of alkynes with the tributylphosphine-carbondisulfide adduct 131 results in the in situ formation of the ylides 132 which react with aldehydes to give the novel 2-arylidene or 2-alkylidene-l,3-dithioles 133 (Scheme 36) [132]. Concerning ylides C-substituted by sulfur we can also mention a publication on the behavior of various keto-stabilized ylides towards acyclic and cyclic a s-disulfides allowing the synthesis of substituted thiazoles, thiols, and dithiols [133]. 

If competitive aldehydes or ketones are used, preferred or exclusive formation of the sterically least hindered alkylidene dipyrazole is observed.[32] If A -carbonyldipyrazole is heated at 190 °C a pyrazole-transfer reaction also occurs to give tetrapyrazole-l-yl-methane in 50% yield.[33]... 

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