Alkylidene derivatives formation

Alkylidene derivatives corresponding to 85 have not yet been reported in the D-ribofuranose series, as evidenced by the formation of the nitrile 82 in high yield. 

Alkylidene derivatives of phthalic thioanhydride are formed as shown in Scheme 160. Reaction of phthalic thioanhydride with hot triethyl phosphite produces trafts-S -bithioph-thalide (457), probably via the carbene and phosphorane (Scheme 161) (72AHC(14)331>. Support for this mechanism stems from the fact that brief treatment of phthalic thioanhydride with triethyl phosphite in the presence of phthalic anhydride gives (458) in the presence of benzaldehyde the same reaction leads to the benzylidene derivative (456). An alternative mechanism has also been suggested, in which the penultimate step is the formation of an epoxide, which is deoxygenated to yield the product (72AHC(14)331>. 

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 afford optically pure 24. Mo-alkylidenes derived from both enantiotopic terminal alkenes in 22 are likely involved. Since the initial metal-alkylidene generation is rapidly 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 meso-bicycle. Such a byproduct is absent from the unpurified mixture containing 23, indicating the exceptionally high degree of stereodifferentiation induced by the chiral Mo com-... 

The reaction between isocyanic acid and allenes was also studied and showed different regiochemistries depending on the substitution pattern (Scheme 35). Thus, in the simplest case (not studied experimentally), the formation of the 4-substituted cycloadduct (141) is predicted to be strongly favored, mainly because of the lower distortion of the allenic moiety at the transition structure (140). In contrast, substituted allenes such as 1,3-dimethylallene form the 3-alkylidene derivative (143) via a more stabilized transition structure like (142), in good agreement with the experimentally observed regiochemistry[113-115]. 

W-Alkylidene derivatives of glycine esters are the preferred starting compounds for the synthesis of unnatural amino acids via the deprotonation/alkylation procedure. Enolate formation is achieved with a strong base (LDA, BuLi, or phosphazene bases such as 2- tert-butylimino)-2-(ethylamino)-l,3-dimethyl-l,3,2-diazaphosphinane) or by phase-transfer catalysis (tetraalkylammonium salts with NaOH or the latter method allows... 

Nucleophilic attack on the 2-chlorine of 126 by triethyl phosphite accounts for the formation of the phosphonates 127, which are useful in the synthesis of 2-alkylidene derivatives analogous to 123 via the Wadsworth-Emmons reaction.139... 

Michael reactions. 2-Alkylidene derivatives of 1,3-dicarbonyl compounds behave as donors in Michael reactions. Of particular interest is the formation of biaryl precursors with quinones. ... 

In contrast to product formation by thermal extrusion of molecular nitrogen from the 4-phosphapyrazoIines (446), photoproduct formation results in deep-seated skeletal rearrangements. Irradiation of the 5-alkylidene derivatives yields the azomethineimines (447), which are spectroscopically detectable and thermally stable in solution. Continued irradiation converts (447) into (449) which opens to give (451). In the case of the 5-arylidene derivative, the ring-contracted product (4 ) is converted to primary photoproduct (450) which aromatises on standing to give (452). ... 

A competing reaction pathway involved in the reaction of FIB(C6F5)2 and Cp2ZrMe2 in hexane is the initial loss of CFl4 and the formation of a transient Zr=CFl2 species which is then complexed by two FIB(C6F5)2 fragments to produce a borane-stabilized alkylidene derivative (42, eq 29). Complex 42 is inactive as an ethylene polymerization catalyst under ambient conditions. 

The optimum conditions for the formation of the 3-lithio derivative of diazepam involved the use of 2 equivalents of LDA in THE at 25 °C. The anion so formed reacted with alkyl halides (e.g., Mel) and esters (e.g., ethyl acetate) to give the 3-alkyl and 3-acyl derivatives (Scheme 12) (77 R = alkyl, acyl). The reaction with aldehydes and ketones furnished carbinols and in the case of benzaldehyde the initially formed carbinol (78 R = Ph) dehydrated to the alkylidene derivative (79) on longer reaction times <81JOC3945>. A similar dehydration was noted also with cyclohexanone. 

Two hydroxyls of a carbohydrate molecule may react with an aldehyde with the formation of a cyclic acetal. These products are known as 0-aryli-dene or 0-alkylidene derivatives of sugars. Acetone condenses similarly to give 0-isopropylidene (acetone) derivatives 2a). 

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). 

In the course of their synthesis of a ring-expanded bryostatin analog 131, Trost et al. studied the RCM cyclization of substrate 128, which was armed for a potential RRCM reaction (Scheme 9.31) [36]. This complex polyene cycUzed very cleanly under the action of [Ruj-III to produce the cyclic diene 129. There was no evidence of formation of the smaller RRCM product The rate of the relay event here is presumably lowered by the pair of quatemized carbons aUylic ( ) and homoallylic (A) to C17 in the alkylidene derived from 128. 

Langer and coworkers constructed diverse O- and N-heterocydic scaffolds, such as y-alkylidene-a-hydroxybutenolides and pyrrolo[3,2-b]pyrrol-2,5-diones, exploiting the well-established cyclization strategy of bisnucleophiles with oxalic acid derivatives [163], while Stockman s research group reported in this context on a novel oxime formation/Michael addition providing the structural core of the alkaloid perhydrohistrionicotoxin [164]. 

There are distinct correlations between the mechanism of formation of compound 43, the eliminations frequently observed with derivatives of aldaric acids, and the reducing power of alkyl D-glucofuranosidurono- and l,2-0-alkylidene-a-D-glucofuranurono-6,3-lactones toward complexed copper(II) solutions. These phenomena are discussed in Section VII. 

Etherification using a metal vinylidene has also been combined with G-G bond formation through the reaction of an alkynyl tungsten complex with benzaldehyde (Scheme 14). The addition of an internal alcohol to the incipient /3,/Udialkylvinylidene that is generated leads to dehydration and the formation of a Fischer-type alkylidene complex. Further reactions of this carbene with a range of nucleophiles have provided access to various furan derivatives.374,375... 

Stang etal. (94JA93) have developed another alkynyliodonium salt mediated approach for the synthesis of y-lactams including bicyclic systems containing the pyrrole moiety. This method is based on the formation of 2-cyclopentenones 114 via intramolecular 1,5-carbon-hydrogen insertion reactions of [/3-(p-toluenesulfonyl)alkylidene]carbenes 113 derived from Michael addition of sodium p-toluenesulfinate to /3-ketoethynyl(phenyl) iodonium triflates 112 (Scheme 32). Replacing 112 by j8-amidoethynyl (phenyl)iodonium triflates 115-119 provides various y-lactams as outlined in Eqs. (26)-(30). 

Stereoselective formation of 3-alkyl-6-methoxy-2,5-piperazine-dione derivatives by the addition of methanol in the presence of NBS to 3-alkyl-6-alkylidene-2,5-piperazinediones was recently reported by Shin et al. 232 The asymmetric induction in this reaction was accomplished by the chiral center of a derivative of the natural proteinogenic chiral amino acid threonine. 

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