Valerolactam, methylation

The combination of CsF with Si(OMe)4 58 is an efficient catalyst for Michael additions, e.g. of tetralone 130 to methacrylamide, followed hy cyclization of the addition product to the cyclic enamide 131 in 94% yield [67]. Likewise, addition of the lactone 132 to methyl cinnamate affords, after subsequent cyclization with tri-fluoroacetic acid, the lactam 133 in 58% yield [68] whereas < -valerolactam 134, with ethyl acrylate in the presence of Si(OEt)4 59/CsF, gives 135 in 98% yield [69]. Whereas 10mol% of CsF are often sufficient, equivalent amounts of Si(OEt)4 59 seem to be necessary for preparation of 135 [69] (Scheme 3.11). 

Besides the activation of the olefinic partner by a metal, the unfavorable thermodynamics associated with the addition of an enolate to a carbon—carbon multiple bond could be overwhelmed by using a strained alkene such as a cyclopropene derivative286. Indeed, Nakamura and workers demonstrated that the butylzinc enolate derived from A-methyl-5-valerolactam (447) smoothly reacted with the cyclopropenone ketal 78 and subsequent deuterolysis led to the -substituted cyclopropanone ketal 448, indicating that the carbometallation involved a syn addition process. Moreover, a high level of diastereoselectivity at the newly formed carbon—carbon bond was observed (de = 97%) (equation 191). The butylzinc enolates derived from other amides, lactams, esters and hydrazones also add successfully to the strained cyclopropenone ketal 78. Moreover, the cyclopropylzincs generated are stable and no rearrangements to the more stable zinc enolates occur after the addition. 

Reaction of 8-valerolactam and ethyl 3-aminocrotonate in boiling phos-phoryl chloride gave 2-methyl-6,7,8,9-tetrahydro-4//-pyrido[l,2-a]pyrim-idin-4-one (91KPS394). 2-terf-Butyl-6,7,8,9-tetrahydro-4/f-pyrido [1,2-a] pyrimidin-4-one 108 was formed when piperidino derivative 107 was allowed to stand in methanol (85JOC166, 85TL3247). 

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... 

The kinetics of the amination of 2-phenoxy-l,3,5-triazine with piperidine was investigated. Instead of the acid autocatalysis (Section 11), a cyclic mechanism is suggested in which a second piperidine, or much more effectively, valerolactam, acts as a catalyst for the amination (75AJI85I). Similar kinetic results are obtained with 3-phenoxyquinazoline (82G167) and 5-methyl-5-phenoxyquinazoline (85JPR865). 

The following abbreviations have been employed for the various lactams BuL for y-butyrolactam (n = 3), NMBuL for N-methyl-y-butyrolactam, Val for 5-valerolactam (n = 4) NMVaL for N-methyl-5-valerolactam, CaL for -caprolactam (n = 5), and NMCaL for N-methyl- -caprolactam. 

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. 

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