8-Valerolactam

Me02C)20, DMAP, CH3CN, 5 min, 71% yield. It appears that only amides having a fairly acidic NH are acylated under these conditions. 6-Valerolactam fails to react. ... 

The first question can be answered relatively simply (although not completely exactly) from the available factual material. If the pK value of the lactam is taken as a criterion, the border of reactivity lies at about pK 12. Valerolactam and caprolactam react just noticeably with diazomethane (yields 14 and 7%). However, it should be noticed that catalysts are frequently necessary in order to initiate the reaction (methanol, water, aluminum isopropylate," fluoboric acid " ). For example, phthalimide does not react at all with diazomethane in ether, but a smooth reaction occurs if some methanol is added. 

Palladium-catalyzed cyclization of iV-alkenyl-2-alkynlamides occurred smothly in the presence of CuClj and LiCl affording valerolactams 103 in moderate yield <96T(52)10945>. 

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). 

The reaction with valerolactam 24 was also investigated, with surprising results. The reaction with BSTFA gave the silyl lactam 78 rather than the silyl imidate 25, as shown in Scheme 3.33. Subsequent reaction with DDQ gave a C-N adduct 79... 

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. 

Six years later, the same authors reported an improved version of their earlier synthesis of ellipticine (228) (527) (Scheme 5.197) by using the l-(p-methoxybenzyl)-5,6-dihydropyridone (1197) as 3,4-pyridyne surrogate (702,703). Thus, the dimethyl-furoindole 544 was treated with the unsaturated lactam 1197 (prepared from 5-valerolactam in three steps) in the presence of trimethylsilyl triflate (TMSOTf) to afford the carbazole 1199 as a single product in 40% yield. The low yield is presumably a consequence of decomposition of the intermediate adduct 1198 during... 

Lactams are named in several ways. They are named as alkanolactams by the IUPAC substitutive system, such as 3-propanolactam, 4-butanolactam, 5-pentanolactam, and 6-hexano-lactam, respectively, for the 4-, 5-, 6-, and 7-membered rings, respectively. An alternate IUPAC method, the specialist heterocyclic nomenclature system, names these lactams as 2-azetidinone, 2-pyrrolidinone, 2-piperidinone, and hexahydro-2f/-azepi n-2-one, respectively. These lactams are also known by the trivial names fl-propiolactam, a-pyrrolidone (y-butyrolactam), a-piperidone (8-valerolactam), and e-caprolactam, respectively. 

Scheme 4.13 (a) Two different types of xanthone-based oxyanion hole receptors developed by Simon and co-workers and (b) possible mode of catalysis of a conjugate addition reaction between pyrrolidine and a, 5-unsaturated valerolactam by one of the receptors. 

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. 

Tetrahydro[l,3]thiazino[3,2-6]isoquinolin-6-one was formed when iV-(3-mercaptopropyl)homophthalimide was heated in o-dichlorobenzene in the presence of p-toluenesulfonic add at 120°C (78BEP866987, 78GEP2756067 79CPB2372). Treatment of jV-(o-acetylthioxybenzoyl)-valerolactam with silver acetate and pyridine in methanol gave 5a-hydroxypyrido[2,l-h][l,3]benzothiazin-ll-one (25) (68AG909). 

Valerolactam lb (10 g, 100 mmol) and LiOHH20 (4.25 g, 100 mmol) were heated to 200 °C to remove water, then under N2 to 270 °C for 4h under reflux. The product 2b and residual 1 were distilled off while the temperature was in-... 

Keywords /V-(aryloylmcthyl)-d-valerolactam, inclusion complex, photocycliza-tion, azetidine... 

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... 

Photocyclization reaction of the V-(aryloylmcthyl)-8-valerolactams (80) occur stereoselectively and enantioselectively in their inclusion crystals with optically... 

Two very elegant alkaloid syntheses basing on intramolecular cycloadditions of imino dienophiles have been published by Grieco and his coworkers. The preparation of ( )-eburnamonine 7-32 is very efficient since imine 7-31, available from (5-valerolactam in a straightforward sequence, is directly converted into the desired alkaloid 7-32 by aza Diels-Alder reaction and subsequent isomerisation of the newly formed double bond. (Fig. 7-8) [506],... 

---