Introducing nitrogen functionality

Displacement of a halide at the a-position with tetramethyl-guanidinium azide (TMGA) introduces nitrogen functionality with inversion of the original halide configuration and <1% epimerization (eq 30). ... 

Another example of the use of Wittig products is shown in Scheme 11.35. Two total syntheses by Chida s group made use of the Overman rearrangement to introduce nitrogen functionality on a tertiary carbon atom [109,110]. This was illustrated by the construction of lactacystin 143, a potent neurotrophic factor found in Streptomyces culture broth. 

When the bromodeoxy lactones were boiled in water tetrahydrofurans were formed, whereas catalytic hydrogenation caused deoxygenation at C-2 and/or at the primary position, while the acetylated aldonolactones could also be reduced to 3-deoxylactones after elimination and stereospecific reduction. Substitution by azide introduced nitrogen functions at C-2 or at both bromo-substituted carbons, and these compounds could be converted into the corresponding amino acids. The new molecules could furthermore be reduced to the corresponding aldoses or alditols. 

Sulphonate displacement reactions have been used to introduce nitrogen functionality. 2-Amino-2-deoxy-D-arabinose has been synthesized in two related nine-step procedures from methyl 3, - -Isopropylldene-D-arablnopyranoside, involving reaction of a 2- -tosyl-D-rlboside with either azide ion or hydrazine. A variety of 1,6-anhydro-2-azido-2-deoxy-6-D-glucopyranose derivatives, of potential as glucosamine monomers in oligosaccharide synthesis, have been obtained from the corresponding 1,6-anhydro-D-mannose 2-trl-... 

In some reactions intramolecular chalcogen nitrogen interactions may lead to stereochemical control. For example, selenenyl bromides react with C=C double bonds, providing a convenient method of introducing various functional groups. The reaction proceeds readily, but affords a racemic mixture. The modified reagent 15.22 contains a chiral amine in close interaction with the selenium atom. It reacts with olefins affording up to 97% ee of isomer A (Scheme 15.2). ... 

The results obtained showed that carbon, oxygen, or nitrogen functionalities are readily introduced into the a,p positions of the lactone moiety. In this way, useful precursors for natural product synthesis are accessible (88TL5317). 

Acetals and ketals are very important protecting groups in solution-phase synthesis, but only a few constructs have been used as linkers in solid-phase synthesis (Tab. 3.3). The THP-linker (22) (tetrahydropyran) was introduced by Ellman [54] in order to provide a linker allowing the protection of alcohols, phenols and nitrogen functionalities in the presence of pyridinium toluene sulfonate, and the resulting structures are stable towards strong bases and nucleophiles. Other acetal-linkers have also been used for the attachment of alcohols [55, 56]. Formation of diastereomers caused by the chirality of these linkers is certainly a drawback. Other ketal tinkers tike... 

Intramolecular 1,3-dipolar cycloadditions have proven to be especially use fid in synthesis. The addition of nitrones to alkenes serves both to form a carbon-carbon bond and to introduce oxygen and nitrogen functionality.86 Entry 7 in Scheme 6.5 is an example. The nitrone B is generated by condensation of the aldehyde group with 7V-methylhydrox-ylamine and then goes on to product by intramolecular cycloaddition. 

Corey reduction is a valuable tool to introduce the chirality in a complex molecule because of its high compability with other reactive centers. Quallich demonstrated that high enantiomeric excesses also were obtained when other heteroatoms were present in the starting material. Specific chelation/protection of nitrogen functions can occur besides the reduction without affecting it (Scheme 16.7).47... 

A related synthesis of 3-substituted fervenulins (394) uses an azo group at the 5-position of the pyrimidine precursor (393) instead of a nitroso group <81H(16)559>. Finally, yet another type of nitrogen functionality at the pyrimidine 5-position is that shown in (396), introduced by treatment of a pyrimidine (395) with diethyl azodicarboxylate. Cyclization of (396) using nitrobenzene or lead tetraacetate affords fervenulin (394) or toxoflavin (397) derivatives <76JCS(Pl)2398>. All these reactions are shown in Scheme 31. 

In order to stereoselectively introduce a nitrogen function on a double bond, a number of methods have been utilized, which conform to the general scheme of activation of the double bond by an electrophile followed by attack of a suitable nucleophile. The geometry of the product depends on the double bond configuration, since all these reactions proceed via anti addition1 -7,215. 

The nature of the nucleophile is critical when considering the Mitsunobu reaction as a means of introducing amine functionalities. Because of the proton transfer components illustrated in the reaction mechanism, only acidic nitrogens can be introduced. The most common nitrogen nucleophiles include phthahmide, hydrazoic acid and zinc azide [62]. Once placed, phthahmides are easily converted to amines utihzing hydrazine [6]. Moreover, azides are easily reduced to amines under numerous conditions [32]. Schemes 6.32 and 6.33 illustrate the application of this chemistry to nucleosides [63] and pyranosides [64], respectively. 

Enantioselective oxidation of olefins is a very elegant way of introducing oxygen and in some cases also nitrogen functions into molecules. The catalytic methods with the highest industrial potential are epoxidation and dihydroxylation, and the kinetic resolution of racemic terminal epoxides (Table 3). 

Nitrogen functions may be introduced following route A (Scheme 2) by using N3 as the nucleophile X which is then reduced by PPh3/H20 to give an NH2 donor function (70). Procedure (A) (Scheme 2), with appropriate modifications, offers itself to the synthesis of tripod compounds with two phosphorus donors and one oxygen or sulfur donor ((82), (90)). 

Basic nitrogen species present on the surface of activated carbons or carbon fibers, like in the case of H2S, were found to enhance the sulfur dioxide uptake. Polyacrylonitrile (PAN)-based activated carbon fibers are examples of good adsorbents for SO2 removal [82, 92]. Although role of nitrogen present in the carbon matrix was not emphasized by Lee and coworkers [93] in their studies of SO2 adsorption on PAN-based activated carbon fibers, [93] Kawabuchi and coworkers noticed a significant increase in the sorption capacity when activated carbon fibers were modified with pyridine and basic nitrogen functionalities were introduced to the surface [93]. Pyridine provided basic functionality, which increased catalytic removal of SO,. . 

Tsuji and coworkers were the first to synthesize a 3-amino-3-deoxyhexuronic acid, in 1968 [22], They began with an isopropylidene glucofuranosiduronic ester and introduced the nitrogen functionality via hydrazone formation and subsequent reduction. Removal of the isopropylidene resulted in formation of amino allouronic acid (Fig. 7). Paulsen and coworkers used a very similar strategy in making 3-amino-3-deoxyglucm onic acid [23]. 

It is also possible to introduce a nitrogen function using these types of process 0-tosylation then t-butylamine as a synthon for ammonia leads to 2-aminopyridines and oxalyl chloride, together with a secondary amide, produces 2-amino-pyridine amides. ... 

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