Lactams butyro

Scheme 11.36. Preparation of 3,4-methano-Y-aminobutyric acid 141 and 4-spirocyclopropane-y-butyro-lactam (145) [109,110,119b].

Trifluoromethylaldimine reacts with various allylic bromides, under Barbier conditions in the presence of indium in DMF, to provide the corresponding homoallylamines (Equation (57)).255 a-Methylene-y-butyro-lactams are prepared by the indium-mediated reaction of 2-(bromomethyl)acrylic acid with aldimines (Equation (58)).256... 

The synthetic utility of this methodology is further demonstrated by hydrolysis and cyclization of Michael adduct 117 to the stereochemically pure butyro-lactam 118 in 79% yield (Scheme 36). The absolute configuration of 118 was assigned by X-ray crystallography of the alkylated derivative 119. 

Reaction of y-butyrolactones with ammonia is a convenient method for preparing ilve-membered ring lactams (2-pyrrolidinone derivatives). When 3-benzyl-7-butyro-lactone (2.23) was heated with ammonia, 4-benzyl-2-pyrrolidinone (2.24) was formed. 13 Hydrolysis led to 3-benzyl-4-aminobutanoic acid (2.25), an anti-spasmodic sedative.l3 Biologically active amino acids are discussed in chapter six. 

The direct vinylogous aldol additions of a,j0-dichloro-y-butenolides and -butyro-lactams have been examined computationally, seeking to identify the origin of the observed diastereoselectivities and especially the reversal observed between the two systems.In addition, reactions with ort/io-substituted benzaldehydes have been 0 compared with those with benzaldehyde itself. 

As part of a projected synthesis of corrins, a simple synthesis of y-substi-tuted y-butyrolactams via the conjugate addition of hydrogen cyanide to unsaturated ketones is described contrary to a much earlier report, the )S-cyanohydrin (101) is not produced, but a mixture of the two butyro-lactams (102) and (103) is isolated, (103) being convertible into (102) by reaction with basic cyanide solution. Reaction of one of those, (102), with potassium t-butoxide in t-butyl alcohol gave, inter alia, the semi-corrinoid (104), These transformations are outlined in Scheme 35. 

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