Nucleophile effects cyclic ether reactions

It was noted early by Smid and his coworkers that open-chained polyethylene glycol type compounds bind alkali metals much as the crowns do, but with considerably lower binding constants. This suggested that such materials could be substituted for crown ethers in phase transfer catalytic reactions where a larger amount of the more economical material could effect the transformation just as effectively as more expensive cyclic ethers. Knbchel and coworkers demonstrated the application of open-chained crown ether equivalents in 1975 . Recently, a number of applications have been published in which simple polyethylene glycols are substituted for crowns . These include nucleophilic substitution reactions, as well as solubilization of arenediazonium cations . Glymes have also been bound into polymer backbones for use as catalysts " " . 

Epoxide (3-member cyclic ether) groups are effective broad-spectrum alkylating agents which have not as yet received a great deal of attention in the design of affinity labels. Their reactions with proteins were first studied by Fraenkel-Conrat (1944) who found that they reacted with the basic forms of most nucleophiles in proteins. Their... 

The indan-based a-amino acid derivatives can be synthesized by PTC. Kotha and Brahmachary [11] indicated that solid-liquid PTC is an attractive method that offered an effective way of preparing optically active products by chiral PTC. They found that ethyl isocyanoacetate can be easily bisalkylated in the presence of K2CO3 as the base and tetrabutylammonium hydrogen sulfate as the catalyst. The advantage of isolating water from the reaction medium is to avoid the formation of unwanted hydroxy compounds in the nucleophilic substitution reaction. If liquid-liquid PTC is applied in the system with the strong base NaOH and dichloromethane as the organic solvent, the formation of dihydroxy or cyclic ether can be observed. 

Nitrogen compounds are also effective as nucleophiles in the anodic oxidation of silyl-substituted ethers. The electrochemical oxidation in the presence of a carbamate or a sulfonamide in dry THF or dichloromethane results in the selective cleavage of the C-Si bond and the introduction of the nitrogen nucleophile at the carbon (Scheme 21) [55]. Since a-methoxycarbamates are useful intermediates in the synthesis of nitrogen-containing compounds [44], this reaction provides useful access to such compounds. Cyclic silyl-substkuted ethers such as 2-silyltetrahydrofurans are also effective for the introduction of nitrogen nucleophiles. The anodic oxidation in the presence of a carbamate or a... 

Similar selectivities (>99 1) are observed in the cyclic chelation controlled reaction of a-benzyloxy carbonyls such as (4a equation 4) with Grignard reagents. However when the a-hydroxy group is protected as a silyl ether (4b), the selectivities observed in the addition reaction diminish (60 40), or reverse (10 90 Table 3). The nonchelating nature of a silyl group, as well as its steric bulk, are responsible for this change in selectivity. In the case of (4b), nucleophilic addition via the Felkin-Anh model effectively competes with the cyclic-chelation control mode of addition. 

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