Lactams medium ring

Keywords Medium-sized ring lactams. Macrocyclization. Ring expansion. Rearrangement, Fragmentation... 

The Baylis-Hillman reaction of TV-protected 3-substituted 4-formylazetidin-2-ones with methyl vinyl ketone has been used to prepare intermediates from which highly functionalised P-lactams fused to medium rings were obtained by radical, stereocontrolled methods <99CC1913>. 

The properties of these compounds resemble those of the simple medium-ring lactams studied by Dunitz and Winkler (1975). A twisted conformation is observed for crystalline caprylolactam, where the preferred trans conformation cannot be properly accommodated in the nine-membered ring. 

In lactams of medium ring size, the amide group is forced into the s-cis conformation. Solid lactams absorb strongly near 3200 cm-1 because of the N—H stretching vibration. This band does not shift appreciably with dilution since the s-cis form remains associated at relatively low concentrations. 

Solid-supported reagents which have found utility include Nafion-scandium Lewis acid catalyst (allyl additions to aldehydes) [62], HOBt (medium-ring lactamization) [63], EDC (preparation of active esters) [64], and thiazolium hydrotribromide (brominations) [65], A review has also appeared describing the use of supported reagents in separation science, primarily for the selective sequestration of metal ions [66],... 

Scheme 7.36 Synthesis of medium-ring lactams and N-hydroxysuccinimide esters employing P-HOBt-derived active esters.

From polystyrene in 3 steps Scheme 7.6J7).268 Preparation of polymeric activesters by reaction with /V-protected amino acids and DCC. Synthesis of medium ring lactams by coupling (o-amino acids to the HOBt resin and subsequent cyclisation. 9... 

Iminium salts, generated in situ from the amides and lactams, react with 1 to produce the corresponding thioamides and thio-lactams, respectively, in good yields (eq T)P- The advantages of this methodology are the easy work-up and chemoselectively amides are thionated in the presence of ketones, aldehydes, and esters (eq 8). ra-Halo acid chlorides react with 1 and the corresponding thiolactones are obtained in moderate yields under mild reaction conditions (eq 9). This reaction works well for the synthesis of small and medium ring thiolactones, but is not useful for the synthesis of macrocyclic thiolactones. ... 

The stereoselective of the ring expansion reaction for the nonracemic 2-pyrrolidine acrylic ester 246 and related systems has been thoroughly investigated by Nubbemeyer. The reaction proceeds via the chair-like transition state 247 and yields 2-azonine 248 with excellent trans-diastereoselection. Products characteristically display E-olefin embedded within a medium-sized ring. Nubbemeyer has studied the relative stability of these slowly interconverting conformers of medium-ring lactams which exhibit planar chirality and effectively demonstrated this chemistry in natural product synthesis. ... 

Buchwald and co-workers developed a simple method for the preparation of medium ring heterocycles (7-, 8-, 9-, and 10-membered). The process employs a Cu-catalyzed coupling of a ) -lactam with an aryl bromide or iodide followed by intramolecular attack of a pendant amino group (Scheme 4.11). In some instanees, the intermediate -lactam was observable but can be converted to the aza-heteroeyele by catalysis. Acetic acid was found to be superior to transition metal eomplexes as a catalyst for this ring-expansion process. 

Bioactivity of novei eight-membered medium ring lactams inspired by octalactin A in murine and human tumor cell lines in vitro... 

Sparks, S. M., Chow, C. P., Zhu, L., Shea, K. J. (2004). Type 2 intramoleculariV-acylnitroso Diels-Alder reaction scope and application to the synthesis of medium ring lactams. Journal of Organic Chemistry, 69, 3025-3035. 

In his cephalosporin synthesis methyl levulinate was condensed with cysteine in acidic medium to give a bicyclic thiazolidine. One may rationalize the regioselective formation of this bicycle with the assumption that in the acidic reaction mixture the tMoI group is the only nucleophile present, which can add to the ketone. Intramolecular amide formation from the methyl ester and acid-catalyzed dehydration would then lead to the thiazolidine and y-lactam rings. The stereochemistry at the carboxylic acid a-... 

Nubbemeyer U (2001) Synthesis of Medium-Sized Ring Lactams. 216 125-196 Nummelin S, Skrifvars M, Rissanen K (2000) Polyester and Ester Functionalized Dendrimers. 210 1-67... 

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