Bicychc lactams

Preparation of Chiral, Nonracemic Bicychc Lactam Substrates... 

Yao, L., Aube, J. (2007). Cation-% control of regiochemistry of intramolecular Schmidt reactions en route to bridged bicychc lactams. Journal of the American Chemical Society, 129, 2766-2767. 

In this case the use of the Doyle dirhodium catalyst Rh2(S-MPPIM)4 (a complex containing the hgand methyl (4S)-2-oxo-3-(3-phenylpropa-noyl)-4-imidazohdine carboxylate) converted the diazoacetate (S)-97 into the ds-flised bicychc lactam (—)-98 in 70% yield together with some dimeric by-products (c. 18%). Elaboration of the piperidine ring entailed lactone cleavage with the anion of phenyl methyl sulfone followed by reduction... 

Lhommet s team has reported a second synthesis of (—)-lupinine (926) based on a convenient multicomponent condensation of the 5-ketoester 1024, (S)-phenylglycinol (1025) and acrolein (Scheme 127). That the reaction yielded a 2 1 mixture of chiral tetrahydro[l,3]oxazolo[3,2-mixture—effectively a masked iminium ion—with sodium triacetoxyborohydride led to the piperidine (—)-1027 as a single isomer. Hydrogenolysis of 1027 followed by treatment with p-toluenesulfonic acid brought about cyclization to the bicycHc lactam (- -)-1028, which underwent reduction of both the ester and the lactam with lithium aluminum hydride to complete this short synthesis of (—)-926. 

Explain why the following bicychc lactam is hydrolyzed at a significantly faster rate than 5-aminopentanoic acid lactam. 

Irradiation of an N-phenacyl-5-lactam in water containing a chiral clathrate produced a single dias-tereomer of the bicycHc lactam in >90% enantiomeric excess. ... 

In the period up to 1970 most P-lactam research was concerned with the penicillin and cephalosporin group of antibiotics (1). Since that time, however, a wide variety of new mono- and bicychc P-lactam stmctures have been described. The carbapenems, characterized by the presence of the bicychc ting systems (1, X = CH2) originated from natural sources the penem ring (1, X = S) and its derivatives are the products of the chemical synthetic approach to new antibiotics. The chemical names are 7-oxo-(R)-l-a2abicyclo[3.2.0]hept-2-ene-2-carboxyhc acid [78854-41-8] CyH NO, and 7-oxo-(R)-4-thia-l-a2abicyclo[3.2.0]hept-2-ene-2-carboxylic a.cid [69126-94-9], C H NO S, respectively. 

All of the naturally-occurring monobactams discovered as of this writing have exhibited poor antibacterial activity. However, as in the case of the penicillins and cephalosporins, alteration of the C-3 amide side chain led to many potent new compounds (12). Furthermore, the monobactam nucleus provides a unique opportunity to study the effect of stmctural modifications at the N-1 and C-4 positions of the a2etidinone ring on biological activity. In contrast to the bicycHc P-lactams, these positions on the monocyclic ring system are readily accessible by synthesis. 

One-step conversion of A-(o)-azidoalkyl)lactams to bicychc amidines, avoiding the protection-deprotection sequence on the amine part, is explored by applying the intramolecular Staudinger-type reaction [26]. Oxalyl chloride [(COCl)2] and bromide [(COBr)2] are found to be effective trigger reagents and the corresponding bicyclic amidines are produced in high yield (Table 3.1). 

Scheme 44 Tin promoted radical preparation of bicychc p lactams 133 (i) PhaSnH (1.2 equiv), AIBN (0.1 equiv), benzene, reflux...

This same group generated bicychc munchnones (e.g., 334) and trapped them with imines to afford either imidazoles 335 or spirocyclic p-lactams 336, depending on conditions, although mixtures are produced and yields of the p-lactams are invariably low (Fig. 4.113). The latter can arise by nucleophilic attack on the munchnone itself or the ring-opened ketene tautomer (vide infra). 

Scheme 1.9 Organocatalytic synthesis of a bicychc P-lactone 1.4.1.2 P-Lactam F ormation...

The group of Murai [14] could demonstrate that ruthenium-catalyzed cyclocar-bonylation of yne-imines resulted in formation of lactams (Scheme 1.4a). Catalytic amounts of Ru3(CO)j2 promote this cyclocarbonylation of 1,6- and 1,7-yne-imines, giving bicychc a,fi-unsaturated lactams. Similar to the Pauson-Khand reaction, the... 

As in the previous coverage of this topic, so numerous are the reported syntheses that routes to the racemic alkaloid rintramolecular acylation at C-2 of the pyrrole 1571 made the alkaloid s C-8/C-8a bond. Yuguchi s intramolecular acylation of pyrrole 1572, by contrast, was a more conventional lactam formation involving nitrogen.The cychzation by Helquist and coworkers entailed reductive... 

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