Denmark modification

A particularly noteworthy variant of the Hiyama coupling is the Denmark modification." Silacyclobutanes... 

It has been shown that bis(chloromethyl)zinc in 1,2-dichloroethane (Denmark s modification) is particularly effective for the cyclopropanation of iodo-substituted allylic alcohols (equation 30) . The cyclopropanation of dihalo-substituted alkenes is a lot more difficult due to the significant decrease in the nucleophilicity of the alkene, thus resulting in much lower yields of the desired products (equation. In this case, significant amounts of 0-methylation were also observed. 

A related reaction is the addition of isonitriles 75 to aldehydes 1 (the Passerini reaction). Denmark has demonstrated that SiCU, upon activation by a chiral Lewis base, which increased the Lewis acidity of the silicon (vide supra Scheme 7.14), can mediate this reaction to produce a-hydroxy amides 77 after aqueous work-up (Scheme 7.16). Phosphoramide 60 was employed as the chiral Lewis-basic catalyst [74]. Modification of the procedure for hydrolysis of 76 gives rise to the corresponding methyl ester (rather than the amide 77) [74]. (For experimental details see Chapter 14.5.5). 

Tandem pericyclic reactions are a powerful strategy for construction of complex, polycyclic compounds. In recent years tandem [4 + 2]/[3 + 2] chemistry of nitro-alkenes and nitronates has been developed by Denmark et al. as a general approach to functionalized pyrrolidine-containing structures [118]. Within the subclass of inter [4 -I- 2]/intra [3 + 2] cycloadditions, they have documented the fused mode (/3-tether, Eq. 77), spiro mode (a-tether, Eq. 78), and bridged mode (a-tether, Eq. 79 or /3-tether, Eq. 80) constructions. These are highly stereoselective processes in the presence of Lewis acid such as SnCU and are amenable to asymmetric modification by use of chiral vinyl ethers. Finally, the nitroso acetals are readily transformed, by hydroge-nolysis, into polycyclic, a-hydroxypyrrolidinones, 4-aminocyclohexanones, and cyclo-pentylamines. 

Subsequent investigations by Denmark have shown that vinylsilanes can direct the course of Nazarov-type cyclization reactions. Once again the regiochemical outcome is controlled by the -effect as substitution takes place at the carbon bearing the silyl group (Scheme 7). This clever modification provided a solution to the serious problem of double bond isomerization that is frequently observed in the classical Nazarov reaction. Treatment of the enone (11) with commercially available anhydrous iron(III) chloride (FeCb) promoted cyclization to give one double bond isomer of the m-hydrindinone (12) in excellent yield. Table 2 summarizes a representative collection of cyclization reactions catalyzed by FeCb. 

Two more examples of PTM databases are O-GLYCBASE [67], a database of O-glycosylated proteins (http //www.cbs.dtu.dk/databases/OGLYCBASE/), and PhosphoBase [68], a database of phosphorylation sites in proteins and peptides (http //www.cbs.dtu.dk/databases/PhosphoBase/). Both databases are maintained by the Center for Biological Sequence Analysis (CBS) in Denmark, which also provides prediction servers for both types of modifications (NetOGlyc and NetPhos). 

The novel mode of Lewis-hase activation of Lewis acid was also applied hy Denmark to the Passerini reaction, the addition of isonitriles 21.119 to aldehydes 21.4 (Scheme 21.17). This reaction produced a-hydro g amides 21.121 after aqueous workup. Phosphoramide 21.104 was employed as the chiral Lewis-hasic catalyst.Modification of the procedure for hydrolysis of 21.120 gives rise to the corresponding methyl ester (rather than amide 21.121). ... 

In November 1986, at a time when only the UK and Denmark had any national legislation specifically to exert control on genetic modification, the Comission of the European Communities (EC) issued a communication to the Council entitled a Community Framework for the Regulation of... 

For those Member States that had existing comprehensive legislation specific to genetic modification work (UK, Germany, Denmark and the Netherlands), the major impact of the Directives is the new pan-European clearance mechanisms for products. For the remainder of the States, the Directives will establish a new statutory framework. 

Denmark has also investigated the carbanion accelerated Claisen rearrangement of allyl vinyl ethers with cydic phosphonamides as carbanion-stabihzing groups [78], because phosphonamide allyl anion is well established and has potential for chiral modification. 

The cyclopropanation of vinyl halides is also effective, with fluoro-, bromo- and iodo-substituted olefins all being suitable substrates. For example, vinyl bromide 16 underwent the reaction in good yield, using Denmark s modification of the reaction (see 1.4.5.1). ... 

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