Paul Sulmon

Synthesis of azetidines from β-chloro imines

Abstract The reaction of β-chloro imines 4 with potassium cyanide in methanol or with lithium aluminium hydride in dry ether gave rise to 2-cyanoazetidines 5 and azetidines 21 . The reaction proceeded by nucleophilic addition of cyanide or hydride across the carbon-nitrogen double bond, followed by ringclosure. The corresponding β-chloro tosylhydrazones, which could either give rise to a four- or five-membered heterocycle on treatment with potassium cyanide in methanol, were shown to afford N-tosylamino 2-cyanoazetidines, exclusively.

Synthesis of 2,2-dialkyl-1-aminocyclopropanecarboxylic acids from α-chloroimines

Abstract 2,2-Dialkyl-ACC analogues, i.e. potential plant growth regulators, were synthesized via straightforward cyclopropanation of α-chloroimines.

Synthesis of 1-amino-2,2-dialkylcyclopropanecarboxylic acids from β-chloroaldimines

Abstract A variety of hydrogen cyanide adducts of β-chloroaldimines using acetone cyanohydrin were prepared. The reactive behaviour of these α-amino-γ-chloronitriles towards bases was investigated with the aim to generate 1-aminocyclopropanecarbonitriles, which are precursors for the potentially plant growth regulating 1-aminocyclopropanecarboxylic acids. The synthesis of 1-amino-2,2-dimethylcyclopropanecarboxylic acid (= 2,3-methanovaline) by a reaction sequence involving addition of hydrogen cyanide across β-chloroaldimines, ring closure to functionalized cyclopropanes and acidic hydrolysis was accomplished. Alternatively the hydrogen cyanide adducts of β-chloroaldimines were converted into α-(N-benzylidene)amino-γ-chloronitriles, which were ring closed with base and hydrolyzed to afford 1-amino-2,2-dialkylcyclopropanecarbonitriles, the latter serving again as substrates for the hydrolytic conversion into the corresponding 1-amino-2,2-dialkylcyclopropanecarboxylic acids (exemplified for 1-amino-2,2-dimethylcyclopropanecarboxylic acid).

A new method for the preparation of β-(alkylamino)-carbonyl compounds by rearrangement of β-chloroimines via azetidine intermediates

Abstract The reaction of β-chloroimines with sodium methoxide in methanol gave rise to β-(alkylamino)- and β-(arylamino)-carbonyl compounds in high yield. The reaction mechanism for the generation of β-(alkylamino)- and β-(arylamino)-carbonyl compounds passes via an intermediate α-methoxyazetidine which is, after ringopening, transformed into a β-(alkylamino)- or β-(arylamino)-carbonyl compund. Only one 2-methoxyazetidine (2-methoxy-2,3,3-trimethyl-1-phenylazetidine) could be isolated under the given reaction conditions. β-Alkylaminocarbonyl compounds were also generated by reaction of β-chloroimines with potassium tert.-butoxide in tert.-butanol or tetrahydrofuran. The latter reaction is initiated by a deprotonation leading, after ring closure, to 2-methyleneazetidines, which are transformed into β-(alkylamino)-carbonyl compounds during the reaction or on workup.

Synthesis of 2,2-dimethyl-1-aminocyclopropanecarboxylic acid from β-chloroimines

Abstract 2,2-Dimethyl-ACC, a potential plant growth regulator, was synthesized by cyclopropanation of β-chloroimines.

Preparation of piperidines from δ-chloroimines

Abstract The reaction of δ-chloro imines with various nucleophiles e.g. metal hydrides, potassium cyanide, alcohols and alkoxides gave rise to piperidines,2-cyanopiperidines and 2-alkoxypiperidines respectively. These piperidines were formed by the addition of the nucleophile across the carbon-nitrogen double bond followed by intramolecular nucleophilic substitution.

1,3-dehydrohalogenation of α-haloketimines as a synthetic tool for the generation of geminally functionalized cyclopropanes.☆

Abstract 1-Alkoxy-1-(N-alkyl)aminocyclopropanes were synthesized by base-assisted alcoholysis of α-haloketimines using tertiary amine bases.

Synthesis of 2,2-dialkylcyclopropylamines from β-chloroimines and application towards the synthesis of1-amino-2,2-dialkylcyclopropane-carboxylic acids

Abstract Base-induced 1,5-dehydrochlorination of β-chloroimines, having a relatively acidic hydrogen atom at carbon-1 of the N-substituent (e.g. benzyl, methoxycarbonylmethyl, α-methylbenzyl), afforded N-cyclopropylimines which were easily hydrolyzed into cyclopropylamines. This synthetic methodology was applied to the synthesis of the potentially plant growth regulating 1-amino-2,2-dialkylcyclopropanecarboxylic acids via oxidation with catalytic ruthenium(IV) oxide/ sodium periodate of suitably N-protected 1-aryl-2,2- dialkylcyclopropylamines.

Unusual ring opening of a Cyclopropylideneamine derivative during a favorskii-type rearrangement of α-Chloroketimines

Abstract The reaction of N-(3-chloro-3-methyl-2-butylidene)amines (i.e. α-chloroketimines) with lithium diisopropylamide in tetrahydrofuran gave rise to an unexpected reaction leading to 2-(N-alkylimino)-3,3-dimethyl-1-isopropyl-5-(2-methylpropylidene) pyrrolidines in good yields. The reaction mechanism is interpreted in terms of a Favorskii-type 1,3-dehydrochlorination affording intermediate cyclopropylideneamines (N-analogues of cyclopropanones), which “dimerize” in an unusual way. This mechanism entails a “normal” opening as well as an “abnormal” opening of incipient cyclopropylideneamine adducts. This rearrangement represents an example of the scarcely reported abnormal opening of functionalized cyclopropylamines.

A novel synthesis of 2-cyano-3,3-dimethylazetidines

A new route to 2-cyano-3,3-dimethylazetidines has been developed by reaction of β-chloroimines with potassium cyanide in methanol which involves nucleophilic addition and subsequent intramolecular nucleophilic substitution.