Bridgehead nitrogen reactions

This methodology has the potential to be generally applicable to the synthesis of various alkaloids that have a bridgehead nitrogen via the intramolecular aza-Diels-Alder reaction (Eq. 12.43).108... 

Linke, S., Kurz,., Lipinski, D., and Gau, W., Annealation reactions of N-heterocycles to condensed pyridones with bridgehead nitrogen, Ann. Chem., 542, 1980. 

The number of methods available for the synthesis of bicyclic systems containing two fused five-membered rings with one bridgehead nitrogen can be summarized in a few general reactions dehydrative ring closure, oxidative Schiff base cyclization, and base-induced closure (Scheme 3). One-pot reactions involving precursor synthesis followed by cyclization are also known. 

Tricyclic P-lactams not having a bridgehead nitrogen atom have been obtained by intramolecular Friedel-Crafls reactions <99T5567> and from the intramolecular Diels-Alder reactions of 1,3-dienes generated from a mesylate 79 <99TL1015>. Other tricyclic P-lactams e.g., 80 have been obtained by intramolecular nitrone-alkene cycloaddition <99TL5391>. 

Most cleavage reactions exclusively proceed by attack on the pyrimidine ring and initially involve fission of the bond between the bridgehead nitrogen and C-7. 

The reaction is generally applicable to further extension for making macrobicyclic diamines4 with bridgehead nitrogen atoms by using monocyclic diimines and an appropriate acid chloride. The main... 

The functional groups can be attached to the macrocyclic ligands by using methods similar to Eqs. (1) and (2). The Ni(II) complexes of pentaaza macrocyclic ligands, 3b-3g, in which functional groups are appended at the bridgehead nitrogen atom, are prepared by the template reaction of [Ni(2,3,2-tet)]2+ and formaldehyde with carboxamide or sulfonamide in the presence of base. The complexes 3b and 3c are... 

A different class of polycyclic naphthoquinone dyes is based on the n apht h 12,361 i ndolizine -6,11 -dione system 14, which is readily accessible by condensation of 2,3-dichloro-l,4-naphthoquinone with active methylene compounds in the presence of pyridine [22], or by reaction of 2-methoxy-3-pyridino-1,4-naphthoquinone with an active methylene compound [23], In 14, the bridgehead nitrogen atom acts as an effective auxochrome, and hence orange to red colors are observed without further substitution. Derivatives of 14 (R = amide group) are of particular value as vat dyes and pigments. Related isomeric heterocyclic structures have also attracted interest, e.g., 15, a yellow disperse dye for polyester [24],... 

Betainic alkaloids and nucleobases, 85, 67 Bicyclic 6/5 ring-fused systems with bridgehead nitrogen, 49, 193 Bifunctional nucleophiles cyclizations and ring transformations on reaction of azines with, 43, 301... 

Several families of efficient chiral phase transfer catalysts are now available for use in asymmetric synthesis. To date, the highest enantiomeric excesses (>95% ee) are obtained using salts derived from cinchona alkaloids with a 9-anthracenylmethyl substituent on the bridgehead nitrogen (e.g. lb, 2b). These catalysts will be used to improve the enantiose-lectivity of existing asymmetric PTC reactions and will be exploited in other anion-mediated processes both in the laboratory and industrially. 

All the bicyclic /3-lactams included in this section have a bridgehead nitrogen atom and are formed from 1,4-disubstituted azetidinones, so this section can be considered as an extension of Section 2.04.9.3. In addition, the Wittig reaction has been extensively employed in the preparation of tricyclic and tetracyclic /3-lactams and its use is referred to in Section 2.04.11. The main use of the reaction to form bicyclic compounds has been to produce 2-substituted carbapen-2-ems. 

The biggest group of tricyclic compounds having a bridgehead nitrogen atom and extra one or more heteroatoms is the fused 4/6/6 system. Two main routes have been adopted for their synthesis either cyclization onto the nitrogen atom of a /3-lactam or by a cycloaddition process. Each of these routes can be achieved by either an intermolecular or an intramolecular reaction. 

The second major route to tricyclic /3-lactams with a bridgehead nitrogen atom and extra heteroatom(s) is through cycloaddition reactions. Again, these may be of the intermolecular or intramolecular type. Diels-Alder reaction of acrolein and the cephems 420 gave 421 as the major products (Equation 65) <1996TL5967>. 

Azine approach. Saturated ring systems with a bridgehead nitrogen atom are best prepared from 3,4,5,6-tetrahydroazine 1-oxides. The latter can be classified as nitrones and as such will undergo 1,3-dipolar cycloaddition reactions. 

Barkworth, P. M. R. and Crabb, T. A.. Compounds with bridgehead nitrogen. XLlll. The reaction between trans-2-amin[Pg.75]

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