Mark Boelens

Electrophile-induced cyclization of γ,δ-alkenylimines as a synthetic route to pyrrolidines and piperidines

Abstract Cyclization of γ,δ-alkenylimines with bromine in dichloromethane gave instantaneous formation of cyclic iminium bromides, which were converted into either pyrrolidines or piperidines, depending upon the substitution pattern. This reaction has been applied in the synthesis of 2-azaspiro compounds.

A Novel Synthesis of 2-imino-4-thiazolines Via Alpha-bromoketimines

A novel straightforward synthesis of 2-imino-4-thiazolines has been performed by reaction of alpha-bromoketimines with potassium thiocyanate in acetonitrile. Contrary to other syntheses of these heterocycles, no side reactions were observed. The structural assignment of these relatively rare 2-imino-2,3-dihydrothiazoles was executed by spectroscopic means, by the synthesis of model compounds by an alternative route and by X-ray crystallographic analysis of an N-acetyl derivative, excluding any other isomeric possibility.

Boron(III) bromide-induced ring contraction of 3-oxygenated piperidines to 2-(bromomethyl)pyrrolidines

Abstract 3-Methoxypiperidines were converted into 2-(bromomethyl)pyrrolidines by reaction with boron(III) bromide in dichloromethane. This reaction proceeds via an intermediate bicyclic aziridinium ion and features a rare conversion of piperidines into pyrrolidines.

Rearrangement of 5-(bromomethyl)-1-pyrrolinium salts into functionalized piperidines.

Abstract 5-(Bromomethyl)-1-pyrrolinium bromides undergo rearrangement with alkoxides in the corresponding alcohol to afford 2,5-dialkoxypiperidines, which are easily converted into 3-alkoxypiperidines. 2,5-Dialkoxypiperidines undergo a peculiar thermal rearrangement to afford 5-alkoxy-1,2,3,4-tetrahydropyridines.

Cyclocondensations of homophthalic anhydrides with 1-aza-1,3-dienes

Abstract α,β-Unsaturated aldimines (1-aza-1,3-butadienes) 2, 4 and 7a-d react with homophthalic anhydrides 1a,b to give 3,4-dihydro-1(2H)-naphthalenone-4-carboxylic acids 3, 5, 8a-d (R2 = H) as main products. Homophthalic anhydride 1a and cinnamaldimine 7d gave rise to the diastereoisomeric naphthalenones 8d (R2 = H), along with the 3,4-dihydro-1(2H)-isoquinolinone-4-carboxylic acids 10 (R2 = H), and 3,4-dihydro-1(2H)-pyridinone 11 (R2 = H) as products of 3,4-, 1,2- and 1,4-addition to the 1-aza-1,3-butadiene, respectively. The effect of the reaction conditions on the ratio of adducts, produced by 1a and 7d, was studied. The structure and relative configurations of 3, 5, 8a-d, 10 and 11 were determined by NMR spectroscopy. In the case of cis-naphthalenone 8c and dihydropyridinone 11, the structure was confirmed by X-ray crystal structure analysis.

Grob-type fragmentation of N-alkyl-2-cyano-5-bromopiperidines to unsaturated imidoyl cyanides

Abstract 2-Cyano-5-bromopiperidines, derived from the stereoselective addition of cyanide to 5-bromomethyl-1-pyrrolinium salts, underwent a Grob fragmentation by reaction with sodium hydride in dimethylformamide, affording unsaturated imidoyl cyanides.

Synthesis of 11H-4b, 10b-dihydro [1] benzopyrano [4,3-c] isoquinoline-6,11 (5H)-diones and 13H-6c, 12b-dihydronaphtho [1′,2′:5,6]-pyrano [4-3c] isoquinoline-8,13 (7H)-dione from homophthalic anhydride and N-(2-hydroxyarylidene) alkylamines

Abstract 2-Alkyl-3-(2-hydroxyaryl)-3,4-dihydro-1(2H)-isoquinolinone-4-carboxylic acids (5,13) were prepared from homophthalic anhydride (1) and N-(2-hydroxyarylidene) alkylamines (2,10). The acids 5,13 showed a tendency towards cyclodehydration to give isoquinoline derivatives with fused [1] benzopyrane (8) or naphthopyrane (12) ring system. The relative configurations of the novel fused heterocyclic compounds 5,8,12,13 and related compounds were determined by NMR studies, and in the case of 13 also by means of X-ray analysis. Some MM2 force field molecular mechanics calculations on some selected fused heterocycles were executed. The naphtho [1′,2′:5,6] pyrano [4,3c]-isoquinoline ring system incorporated in the lactone 12 is hitherto unreported.

Stereospecific aziridination of olefinsviaelectrophile-induced cyclization of γ,δ-unsaturated imines and subsequent hydrolytic rearrangement

The olefinic bond of γ,δ-unsaturated aldehydes underwent a net aziridination through electrophile-induced cyclization and subsequent rearrangement of the resulting cyclic iminium salts: this methodology allows the stereospecific introduction of aziridine moieties into cyclic systems.

Enantioselective Synthesis of (-)-(6R,7S)-Nitramine

The spirocyclic (-)-(6R,7S)-nitramine was prepared in a straightforward way from an appropriately substituted chiral α-allylaldimine precursor involving an electrophile-induced cyclization as the key step.

Organoselenium-induced cyclization of ?,?-alkenimine to nitrogen heterocycles

γ,δ-Alkenimines undergo electrophile-induced cyclization by means of phenylselenenyl bromide to produce cyclic iminium salts which are reduced to functionalized pyrrolidines or piperidines.