S-Valerolactam

An ab initio study of the acid hydrolysis of the lactam l-azabicyclo[2.2.2]octan-2-one (described as a highly twisted amide ) and of the model compound 3-methyl-S-valerolactam showed that both proceed via a stepwise mechanism, but A-protonation is preferred to O-protonation by the twisted amide , whereas the reverse is the case for the model compound.92... 

A second type of study that corroborates the basic assumption is any measurement which specifically shows that the H bonded species are cyclic. Infrared data can offer such evidence, provided the only important species over a wide concentration range are monomers and dimers. For such a system the peak intensities of absorption by the monomer (Im) and dimer (Id) are simply related the ratio IdIIm is a constant. Such behavior has been observed and cited in favor of cyclic dimers of S-valerolactam and of -caprolactam by Tsuboi (2050), and of y-bu-tyrolactam by Klemperer et al. (1117). However, no such deduction can be made for other amides (e.g., see 1117), phenols (e.g., see 411), or alcohols (e.g., see 1375 and 1150). There is much evidence in favor of cyclic dimers of carboxylic acids in the gas phase (1081), and some referring to solutions (1652 and 445). On the other hand, the IR data for liquid formic acid are more complicated. Ghapman (373) concludes that the liquid contains a mixture of cyclic dimers and chain polymers. Dielectric data have been interpreted to show that formic acid is not entirely dimeric (1046). By use of thermo-electric osmometry Davies and Thomas have measured AH of dimerization of several amides and have concluded that trichloroacetamide and A -methyltrichloroacet-amide form cyclic dimers, whereeis iV-methylaceteunide, iV-methylform-... 

Draw the structure of each of the following compounds (a) /3-butyrolactone (b) /3-valerolactone (c) S-valerolactone (d) /3-propiolactam (e) a-methyl-S-valerolactam (f) iV-methyl-y-butyrolactam. 

Reddy PA, Woodward KE, Mcllheran SM, Hsiang BCH, Latifi TN, Hill MW, Rothman SM, Ferrendelli JA, Covey DR Synthesis and anticonvulsant activities of 3,3-dialkyl-and 3-alkyl-3-benzyl-2-piperidinones (S-valerolactams) and hexahydro-2H-azepin-2-ones (e-caprolactams). J. Med. Chem. 1997 40 44 9. 

Friestad and co-workers recently demonstrated that N-acyl hydrazones were excellent radical acceptors in the presence of a chiral Lewis acid [84], Valerolactam-derived hydrazone 117 proved to be the optimal substrate for enantioselective radical additions. Upon further optimization it was found that Cu(OTf )i and f-bulyl bisoxazoline ligand 96 gave the best yields and ee s (Scheme 31). Interestingly, a mixed solvent system (benzene dichloromethane in a 2 1 ratio, respectively) in the presence of molecular sieves (4 A) were necessary to achieve high yields and selectivities. 

Enantioselective free-radical additions to N-acyl hydrazones mediated by chiral Cu(II) Lewis acids have been demonstrated by Friestad and coworkers [16]. Addition of a variety of alkyl radicals to valerolactam-derived N-acyl hydrazone (54) catalyzed by one equivalent of dehydrated [Cu((S,S)-tBu-box)(H20)2(OTf)](OTf) (55) proceeds with moderate to good yield and high enantioselectivity (Scheme 17.11). Catalytic loadings could be decreased without loss of reactivity, but significant erosion of enantioselectivity was observed. Nevertheless, this methodology represents a viable alternative to classical Strecker and Mannich reactions for asymmetric amine synthesis. 

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