Lactam amines from

Lukes studied the reaction of N-methyl lactams with Grignard reagents. With the five- (39-42) and six-membered (43-47) rings, 2,2-dialkylated bases (16, = 1,2) are formed as by-products in addition to the l-methyl-2-alkyl pyrrolines (15, = 1) or l-methyl-2-alkyl piperideines (15, =2). Aromatic Grignard reagents afford only the unsaturated bases, probably because of steric factors (48,49). Separation of enamines and 2,2-dialkylated amines from each other can be easily achieved since the perchlorates of the enamines and the picrates of 2,2-dialkylated bases crystallize readily. Therefore enamines can be isolated as crystalline perchlorates and the 2,2-dialkylated bases as crystalline picrates. Some authors who repeated the reactions isolated only pyrrolines (50,57) or, by contrast, 2,2-dialkylated bases (52). This can be explained by use of unsuitable isolation techniques by the authors. 

The lactam formation from the oxidation of cyclic amines (353, for example) probably proceeds via intermediate 364. The nitrogen-iodine bond dissociates to give imine 365, which reacts again with a second equivalent of iodosobenzene to give another intermediate 366. Finally, 366 on reductive... 

Similarly, both acyclic and cyclic allyl amine derivatives have been applied in 1,3-dipolar cycloadditions (134-138). Langlois et al. (139) used a,()-unsaturated-y-lactams derived from (5)-pyroglutaminol, such as 91 and 92, in the 1,3-dipolar cycloaddition with the A -benzylnitrone derived from formaldehyde (Scheme 12.30). For compound 91, one of the 1,3-dipolar cycloaddition product isomers obtained... 

From the comparison of ionization constants it was also deduced that both 1-methyl and 3-methyl cytosines exist predominantly in the lactam-amine forms 2 and 3, respectively.100,102 The conclusions based on a comparison of ionization constants have been confirmed by UV analysis (see below). 

The near UV absorption spectra of cytosine, cytidine, and their derivatives have been measured in different solutions and in the solid state. Early works by Stimpson and O Donnell38 were thought to confirm the previous conclusion from IR evidence that cytosine exists in the lactim-amine form 1. However, all later UV studies indicate that the predominating form both of cytosine and cytidine is lactam-amine... 

A practical method for the synthesis of gem-2,2-disubstituted tertiary amines from the corresponding lactams (or amides) has been reported. It is based on the reaction of thioiminium ions, easily prepared from lactams and amides with primary alkylcerium reagents.40... 

The dicarbonyl compoimd 51 was oxidized to the anhydride 52, which subsequently reacted with primary or secondary amines to form a-amino acids, a-amino amides and dipeptides 53 (Scheme 14) [48]. 3-Hydroxy j8-lactams obtained from imines derived from carbohydrates [49,50] or prepared via the Sharpless AD reaction [51-53] were directly oxidized to anhydrides by treatment with NaOCl and TEMPO. Anhydrides 54-56 were used for the synthesis of compounds related to the family of polyoxins represented by 57 (Scheme 15) [49-53]. 

Acylation of Amines. Acylation of amines is also faster in the presence of DMAP, as is acylation of indoles, phosphorylation of amines or hydrazines, and conversion of carboxylic acids into anilides by means of Phenyl Isocyanate /3-Lactam formation from /3-amino acids has been carried out with DCC-DMAP, but epimerization occurs. ... 

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

Schiff bases s. Azomethines Schlotterbeck s. Buchner Schmidt reaction 17, 524 —, amines from carboxylic acids 19, 305 20, 366 —, lactams from ketones, cyclic, ring expansion... 

In a model study, the saturated 14-membered D ring of madangamine D was assembled by two alternative methodologies, lactamization and reductive amination, from the 3,3-disubstituted piperidine derivatives 78 and 79, which incorporate the required 11 -carbon chain, ending with either a car-boxy or a formyl functionality. These precursors were prepared by controlled oxidation of alcohol 77, which in turn was obtained from 2-piperidone 76, as outlined in Scheme 18. Operating under high-dilution conditions, acid 78 was converted to macrocychc lactam 80, whereas aldehyde 79 afforded macrocychc amine 81." ... 

Pingen D, Vogt D (2014) Amino-alcohol cyclization selective synthesis of lactams and cyclic amines from amino-alcohols. Catal Sci Technol 4(l) 47-52... 

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). 

Allylic phosphates are used for carbonylation in the presence of amines under pressure. Carbonylation of diethyl neryl phosphate (389) affords ethyl homonerate (390), maintaining the geometric integrity of the double bond[244]. The carbonylation of allyl phosphate in the presence of the imine 392 affords the /3-lactam 393. The reaction may be explained by the formation of the ketene 391 from the acyl phosphate, and its stereoselective (2 + 2] cycloaddition to the imine 392 to give the /3-lactam 393(247],... 

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