Dihydropyridine / -lactam

Lactam 86, when treated with diisobutylaluminium hydride (DIBAL-H), led to a 6 2 1 mixture of 89b, 90b, and 91b (95% combined yields) (Scheme 20) <1996T3563>. In the case of reaction of 83 with l-(2-hydroxy-l-phenylethyl)-5,6-dihydropyridin-2(l//)-one, an equimolecular mixture of cis- and trans-lactams of type 85 (R = CH(Ph)CH2OH, R = R2 = H) was obtained in 88% yield. Reduction of the trans-lactam with Red-Al gave the diazocine 89 (R = CH(Ph)CH2OH) and an analogue of 91 with an oxazolidine ring annelated to the piperidine moiety <1995TL1693>. 

Charette recently described an innovative activation protocol in which lactams, in the presence of triflic anhydride (33), react with pyridines to afford the pyridinium imidate 107 in good yield. Subsequent addition of metal enolates to this species leads to 2-substituted tricyclic dihydropyridines, advanced intermediates for the total synthesis of the natural alkaloid ( )-tetraponerine T4 (109, Scheme 16) [107]. 

Unsubstituted cyclopropylamine (77) gave a mixture of 486 and ammonia upon thermolysis (equation 123). 486 is formed from the product of a homoenamine reaction 485 and excess 77. Intermediate 484 (R = H) was observed by the IR spectrum in the gas phase The reaction 485 - 486 did not take place with ethylaminocyclopropane (483) in this case 485 (R = Et) could be isolated . Insertion of carbon monoxide into the vicinal carbon-carbon bond of 77 in the presence of rhodium catalysts produced y-lactams . Thermolysis of a homoazepine led to a vinyl dihydropyridine , heating of a homopyrrole or bishomopyrrole gave products derived from an azomethine ylide intermediate ... 

A 3-oxopropyl side-chain reacts with a lactam carbonyl [as in (102.3] and a source of ammonia such as ammonium acetate to form a fused dihydropyridine ring. 

There are two other classes of dienyl lactams that have been used synthetically, A -alkyl-2-pyridones (160) and Al-acyl-l,2-dihydropyridines (161). Pyridones tend to be relatively unreactive, requiring high temperatures and often giving low yields of the cycloadduct.Al-Acyl pyrrole derivatives also function as diene partners in the Diels-Alder reaction. 

Ketene-imine cycloaddition involving an imine derived from cinnam-aldehyde and a D-glucosamine derivative led stereoselectively to the p-lactam (110) the chiral auxiliary could be disconnected from the p-lactam by base treatment. Cycloaddition of methyl acrylate and an N-glycosyl dihydropyridine gave adduct (111) and its diastereomer in the azabicyclic ring system. Removal of the chiral auxiliary from each diastereomer then gave the enantiomeric isoquinuclidines. ... 

Cyclization on to unsaturated C=N bonds has been reported by a number of workers to proceed in the unusual 6-endo fashion preferentially. Generation of the initial radical by addition of either a tin-centred or a sulfiir-centred radical to an alkyne or allene has been demonstrated. Thus cyclization of vinyl radicals (produced by the BusSnH-mediated addition to alkynes) on to imines proceeds in a 6-endo manner to give functionalized piperidines (Scheme 21). In a similar manner, allyl radicals (generated by Ts addition to allenes) add in a 6-endo manner to hydroxylamine derivatives. EUmination of the RO leads to the formation of dihydropyridines (Scheme 22). Functionalized bicyclic j8-lactams can be produced by an unusual 1-endo cyclization triggered by a similar addition of a tin-centred or sulfur-centred radical to substituted Af-propargyl )3-lactams. ... 

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