Lactams amines, cyclic

Formation and transformations of cyclic amines and lactams 98JCS(P1)2959, 99JCS(P1)2209. 

We have previously seen how cyclic lactams can be synthesized by installing a protected amine in one of the Ugi or Passerini components, followed by cyclization onto the isocyanide-derived amide, taking advantage of the particular reactivity of convertible isocyanides. The same type of compounds can be accessed through nucleophilic attack of the amine onto an ester moiety, suitably installed as additional function into another component. This strategy has been widely used for the preparation of diketopiperazines 104 (Fig. 22), a typical privileged structure, starting with... 

Oxidation of cyclic t-amines.1 Hg(OAc)2 in combination with ethylenedi-aminetetraacetic acid (EDTA) is the classical reagent for dehydrogenation of t-amines (1, 648). This reaction can be used to convert cyclic t-amines to lactams. 

Another general method for the introduction of a nitrogen atom into a macrocyclic skeleton is via the Beckmann reaction. Rearrangement of cyclotridecanone oxime led to cyclic lactam, which was reduced to amine by lithium aluminium hydride (LAH). Further substitution yielded 14-membered mutuporamine <1999TL5401>. Dieckmann condensation was used for the preparation of 14-membered aza ketone 15 <1999JA2919>, but no experimental details were given. 

In a very early example, Freidinger et al. developed a series of cyclic lactams that stabilized j8- and y-turn structures in linear peptides (Fig. 15.8). This strategy was applied to determine conformations of LH-RH that are consistent with the turn structure permitted by the constraint. For example, the 3-amin-olactam (18)was used to mimic a p-turn conformation. When inserted in LH-RH, com-... 

Both phenylacetic and 3-phenylpropionic acids (120) easily undergo the Schmidt reaction under the standard conditions using sulfuric acid, giving the corresponding amines (121). 4-Phenylbutyric acid (122), however, produces the cyclic lactam (123), in addition to the sulfonated amine (124). Replacement of sulfuric acid with polyphosphoric acid again affords the lactam (123) mainly, together with 3-phenylpropylamine (125) as a minor product. In the rearrangement of S-phenylpentanoic acid (126), only the sulfonated amine (127) is obtained, as shown in Scheme 24. 

Sodium tetrahydridoborate I alcohols Cyclic amines from lactams s. 44, 72... 

Cyclic monomers that have been polymerized via ring-opening encompass a variety of structures, such as alkanes, alkenes, compounds containing heteroatoms in the ring oxygen [ethers, acetals, esters (lactones, lactides, and carbonates), and anhydrides], sulfur (polysulfur, sulfides and polysulfides), nitrogen [amines, amides (lactames), imides, N-carboxyanhydrides and 1,3-oxaza derivatives], phosphorus (phosphates, phosphonates, phosphites, phosphines and phosphazenes), or silicon (siloxanes, silaethers, carbosilanes and silanes). For the majority of these monomers, convenient polymerization conditions have been elaborated, that result in the controlled synthesis of the corresponding polymers [1-13]. 

The cyclic carbonate of benzoin (4,5-diphenyl-l,3-dioxol-2-one, prepared from benzoin and phosgene) blocks both hydrogen atoms of primary amines after dehydration acid stable, easily crystallizable Sheehan oxazolinones are formed, which are also called Ox derivatives. The amine is quantitatively deblocked by catalytic hydrogenation in the presence of 1 equiv. of aqueous acid (J.C Sheehan, 1972, 1973 M.J. Miller, 1983). An intelligent application to syntheses of acid labile -lactams is given in the previous section (p. 161). 

In addition to alcohols, some other nucleophiles such as amines and carbon nucleophiles can be used to trap the acylpalladium intermediates. The o-viny-lidene-/j-lactam 30 is prepared by the carbonylation of the 4-benzylamino-2-alkynyl methyl carbonate derivative 29[16]. The reaction proceeds using TMPP, a cyclic phosphite, as a ligand. When the amino group is protected as the p-toluenesulfonamide, the reaction proceeds in the presence of potassium carbonate, and the f>-alkynyl-/J-lactam 31 is obtained by the isomerization of the allenyl (vinylidene) group to the less strained alkyne. 

Reduction of cyclic hydroxamic acids generally leads to lactams or the corresponding amines. Chemical methods have frequently been preferred to catalytic hydrogenation, probably because the choice of... 

The reaction is effective with both acyclic and cyclic amides., or lactams, and is a good method for preparing cyclic amines. 

---