Benzyl and Related Derivatives

Double n -aza-allyl-lithium interactions have been found in the solid state structure of 2,6-(MegSiCHLi)2-pyridine.2THED in agreement with a MNDO 

Solvent effects on the C n.m.r. spectra of indenyl-lithium have been investigated. The pyrolysis of 9-Li-fluorene at 180 C provides 9,9-Li2 fluorene. An equilibrium lithium ion-pair indicator scale has been established for a series of fluorenederivatives which form solvent separation ion-pairs in THF AS values were found to be small for the indicator equilibria, studied by u.v.-vis spectroscopy.  

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Hydroxycarbonylation and alkoxycarbonylation of alkenes catalyzed by metal catalyst have been studied for the synthesis of acids, esters, and related derivatives. Palladium systems in particular have been popular and their use in hydroxycarbonylation and alkoxycarbonylation reactions has been reviewed.625,626 The catalysts were mainly designed for the carbonylation of alkenes in the presence of alcohols in order to prepare carboxylic esters, but they also work well for synthesizing carboxylic acids or anhydrides.137 627 They have also been used as catalysts in many other carbonyl-based processes that are of interest to industry. The hydroxycarbonylation of butadiene, the dicarboxylation of alkenes, the carbonylation of alkenes, the carbonylation of benzyl- and aryl-halide compounds, and oxidative carbonylations have been reviewed.6 8 The Pd-catalyzed hydroxycarbonylation of alkenes has attracted considerable interest in recent years as a way of obtaining carboxylic acids. In general, in acidic media, palladium salts in the presence of mono- or bidentate phosphines afford a mixture of linear and branched acids (see Scheme 9). 

Due to their high selectivity, DER and DEL were the basis for an extensive structure activity relationship study aimed to understand the essential requisites of p. and 8 activity. More than 200 analogues of DER and DEL C were synthesized, and the role of each amino acid in binding to p and 8 receptors and bioactivity was defined [21-31]. New synthetic products were prepared such as oxymorphindole and related derivatives [32], and (+)-4-[(alfa R)-alfa-((2S,5R)-4-allyl-2.5-dimethyl-l-piperazin-yl)-3-methoxy-benzyl]-N, diethylbenzamide [33]. These products are under investigation for their clinical relevance and provide potential nonpeptide ligands for studies on delta-opioid-receptor. 

Secondary aliphatic acids, esters and related derivates Mononuclear phenolic compounds Depsides, tridepsides and benzyl esters Depsidones and diphenyl esters Depsones... 

Hetero-benzylic anionic reagents, derived from 2-alkyl-l,3-oxazoles, -1,3-thiazoles and -imidazoles and related compounds, are not covered in this section because these resemble metallo 1-azaenolates in their reactivity (Section D.l.3.5.). 

The Mukaiyama condensation method was also utilized in the synthesis of several antibiotics and related bioactive substances. These syntheses include apramycin, using 4-azido-2,3,6-tri-(P-benzyl-4-deoxy-) -D-glucopyranosyl fluoride (prepared from the corresponding a-D-glucopyranosyl chloride by the AgF method ) avermectin B , using protected sugar derivatives of oleandrosyl fluoride (a-L-Ole-F) and 0-(a-L-01e)-(1 4)-a-L-0le-F (both... 

Two classes of a-hydroxylated lignans have been enantioselectively prepared a) wikstromol (3) [10, 38] and related natural products [39] and b) gomisin A (1) and congeners [40, 41]. In both cases, chiral, non-racemic ita-conic acid derivatives have been synthesized as key compounds for the preparation of -benzyl-y-butyrolactones (either by resolution (g [32]) or by asymmetric hydrogenation (h [25])). 

Alkenyl derivatives of benzyl alcohol and related naphthalene substrates undergo a rapid Pd-catalysed cyclisation to U/-2-benzopyrans and the bettzologues (Scheme 14) <99TL4871>. 

In a related type of reaction, the styryl isocyanates, readily available by Curtius rearrangement of cinnamoyl azides, undergo thermal cyclization to l-isoquinolones in good yield (equation 34) the reaction can also be carrried out using Friedel-Crafts catalysts. 2,3-Dihydro-4( 1//)- isoquinolones are obtained by Dieckmann cyclization of N- (o- carbalkoxy-benzyl)glycine ester derivatives (equation 35). The same reaction has been used for the synthesis of a range of non-aromatic heterocycles (equations 36 and 37). 

In the original investigation of the Pd- or Ni-catalyzed alkenyl-benzyl and benzyl-alkenyl coupling reactions168, both Pd- and Ni-phosphine catalysts were shown to be effective. In some Ni-catalyzed reactions, however, double-bond migration to produce styrene derivatives was observed as a side reaction169. Nonetheless, both Pd- and Ni-catalyzed procedures have been successfully applied to the synthesis of various coenzymes Q , where n is < 10, and related menaquinones (Scheme 63)171,172. 

Whereas allyl, benzyl and propargyl electrophiles are among the most reactive towards Pd, Ni and other transition metals, ordinary alkyl halides and related alkyl electrophiles that are not /3, -unsaturated are among the least reactive carbon electrophiles with respect to oxidative addition to Pd or Ni. Most of the alkyl derivatives are also associated... 

For related reasons, and because their excited-state energies are lower than for dialkyl ketones, diaryl ketones and simple alkyl aryl ketones do not fragment on irradiation in solution, even at higher temperatures. This leads to a photostability that is one factor contributing to the successful employment of ketones such as benzophe-none tPh-CO) or acetophenone (PhCOMe) as triplet sensitizers. a-Cleavage for ketones in solution at room temperature is promoted if structural factors cause the bond adjacent to the carbonyl group to be somewhat weaker than normal. Hence t-alkyl ketones give decar-borylation products readily (4.5), as do benzyl ketones (4.6 and benzoin derivatives (4.7). 

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