Synthesis of substituted piperidines, decahydroquinolines and octahydroindolizines by radical rearrangement reactions of 2-alkylideneaziridines

Regioselective synthesis of substituted piperidine-2,4-diones and their derivatives via Dieckmann cyclisations

“…Subsequent alkylation at the b-position was also possible, ester 1b being converted into 1d. Reaction of b-keto esters 1 with ammonium acetate in the presence of acetic acid afforded the vinylogous carbamates 2, which were reduced with sodium triacetoxyborohydride prepared in situ 14 to give the corresponding b-amino esters 3. The latter were coupled with monomethyl malonate using EDC in the presence of HOBt to give the amidodiesters 4.…”

“…Use of the Davies 18 conjugate addition of (S)-N-(a-methylbenzyl)allylamine (7) to a,b-unsaturated esters afforded enantiopure b-amino esters that also underwent Dieckmann cyclisation to give, after hydrolysis and decarboxylation, the corresponding substituted piperidine-2,4-diones; the chiral auxiliary was cleaved using methanesulfonic acid, thereby achieving some enantioselective syntheses of substituted piperidine-2,4-diones without 1-substitution. Synthesis of substituted piperidine-2,4-diones can be used to access to a variety of congeners of alkaloids or other pharmacologically active compounds, including 4-hydroxypiperidin-2-ones, the corresponding substituted piperidin-2-ones and piperidines; examples herein include the piperidine-2,4-dione 12g, an analogue of anabasine, and (4R,6R)-4-hydroxy-6-phenylpiperidin-2-one (14) prepared by reduction of 6f with LiAlH 4 .…”

Synthesis and applications of methyleneaziridines

“…Shipman et al rst found that the alkyl radical 111, generated from a suitable precursor such as 108, could undergo 5-exo-trig cyclization to form aziridinylcarbinyl radical 112, which was transformed to aminyl radical 113 via N-C2 bond cleavage then provided piperidine derivatives in moderate yield (Scheme 35). 50 Using this radical cascade methodology, they also achieved a tandem radical process to form indolizidine 110 in 39% yield (dr ¼ 4 : 1). 51…”

Methyleneaziridines: Unusual Vehicles for Organic Synthesis

“…10 As 22 is readily made by the addition of dibromocarbene to the corresponding alkene, this route is convenient for the synthesis of a number of gem-disubstituted precursors. 22,25,27,28 (R = CPh 3 , R 1 , R 2 = H) by reacting amine 23 with trityl chloride. 6 Despite the harsh reaction conditions employed in the cyclization, many functional groups survive unscathed (Figure 2).…”

“…A range of phenylselenyl-substituted methyleneaziridines were prepared for cyclization studies including 96-99. 22,65 Slow addition of tri-n-butyltin hydride and AIBN over several hours in benzene via a syringe pump to a dilute {final [substrate] = 0.015 M} refluxing solution of these substrates in benzene provided the rearranged products 100-103, respectively, in good yields (Scheme 26). In some instances, product isolation was facilitated by in situ Boc protection of the product to reduce volatility and water solubility.…”