W.N. Speckamp

Intramolecular reactions of N-acyliminium intermediates

Generation des ions N-acyliminiums et syntheses de leurs precurseurs; amidoalkylations intramoleculaires avec des π-nucleophiles aromatiques; reactions de π-nucleophiles non aromatiques; utilisation des composes a methylene actif; reactions pericycliques

A regioselective reduction of gem-disubstituted succinimides

Abstract The NaBH4 reduction of mono- and disubstituted succinimides in the presence of hydrochloric acid leading to ω-carbinol-lactams shows a remarkable regio- and/or stereo-selectivity. The reduction takes place at the most substituted CO in the succinimides. Possible explanations are reviewed. The preparative value of the method is amply illustrated.

On the nature of sigma-coupled transitions : Through-bond interactions in 1-aza-adamantane derivatives

Abstract 1-Aza-adamant-4-one and a number of its derivatives, in which the CO function is modified, show absorption in the near UV region which is attributed to a sigma-coupled transition. From absorption and emission spectroscopic data it is shown that this transition has to be charge transfer in character and that it derives its intensity mainly from a local π-π* transition in the (modified) CO group. From the relative basicities, the IR spectra and the 13 C NMR spectra it is concluded that the amount of charge transfer in the electronic ground-state is very small for the compounds studied.

Mitomycin analogs. I: Indoloquinones as (potential) bisalkylating agents

Abstract Catalytic reduction (H2, PtO2-EtOH) of indoloquinones 7 affords indoloquinones 8 . Depending on their leaving group ability one or both substituents X and Y can be eliminated. Evidence is provided, on carrying out the reduction reactions in EtOD, for the intermediacy of quinone methides 10 , 12 and/or 13 and iminium derivatives 14 .

Biomimetic α-acylimmonium cyclisations of unactivated olefin

Cyclisation of olefinic ω-ethoxylactams 9-16 leads to ringclosed products in excellent yields. The reaction is weakly acid-catalyzed, in several cases also stereospecific and proceeds at ambient temperature. The structure and configuration of the products are discussed. Possible relationships with other immonium cyclisations and with cationic carbocyclic olefincyclisations are reviewed. The cyclisation of one example—13b—deserves special attention because of the concomitant operation of synchronous and stepwise cyclisation mechanisms.

Biomimetic heterocyclisation of aryl olefins one-step formation of two carbon-carbon bonds

Cyclisation of ethoxylactam 5 in formic acid at room temperature gives rise to stereospecific formation of 9. Similar reaction of the olefin 6 possessing unnatural geometry also proceeds stereospecific and in quantitative yield to the tetracyclic product 10. The acetylene 7 equally affords 11. Upon Me-substitution of the olefinic double bond the cyclisation of 8 has to be carried out in trifluoroacetic acid-dichloromethane in order to obtain a 84% yield of 12 again formed with a high degree of stereoselectivity. The results are discussed on the basis of a mechanism involving synchronous bond formation.

Through-bond interaction in 1-aza-adamantane derivatives

Abstract The photoelectron spectra of 1-aza-adamantane, 1-aza-adamant-4-one and 1-aza-adamant-4-methylene are described and compared with those of the corresponding adamantane analogues. In the 1-aza-adamantane derivatives a through-bond interaction between the nitrogen lone-pair and the 4-substituent is observed. This through-bond interaction is discussed in relation with the sigma-coupled transition observed in the electronic absorption spectrum of 1-aza-adamantane derivatives, and in relation with their relative basicity both in solution and in the gasphase.

Oxazaborolidine catalysed enantioselective reduction of cyclic meso-imides

Abstract Full details of the enantioselective reduction of cyclic meso -imides catalysed by an enantiopure oxazaborolidine derived from ( S )- α , α -diphenylprolinol are reported. Treatment of the imides with borane in the presence of the catalyst led to a mixture of cis - and trans -hydroxylactams and, after subsequent ethanolysis, to the corresponding diastereomerically pure trans -ethoxylactams. The enantiomeric excesses were shown to be 68–94% by HPLC-determination. One example, in which the ethoxylactam was converted into the benzenesulfonyllactam, could be crystallized to >99% enantiomeric purity.

Formamide as a superior nitrogen nucleophile in palladium(II) mediated synthesis of imidazolidines

Formamides emerge as superior nitrogen nucleophiles in palladium(II) catalyzed oxidative 5-exo cyclizations of formaldehyde aminals derived from N-Boc protected allylic amines. The product imidazolidines are readily transformed into protected vicinal diamines.

Studies on the role of the 2-oxonia Cope rearrangement in p-cyclizations of a-methoxycarbonyl oxycarbenium ions.

Abstract The 2-oxonia Cope rearrangement is shown to play an important role in Lewis acid-induced π-cyclization reactions of a variety of methyl 2-acetoxy-2-(3-alken-1-oxy)acetates to 5- and 6-membered ring ethers. The influence of this [3,3]-sigmatropic rearrangement on the regio- and stereochemical outcome of the cyclization is evaluated by studying three types of substrates, namely (1) four chain-substituted precursors, (2) three silicon-substituted precursors (allyl- and vinylsilanes) and (3) two enantiopure precursors. Controlling factors are the nature of the π-nucleophile and the substitution pattern of the oxycarbenium ion intermediate. The absolute stereochemistry is retained in the cyclization of the enantiopure substrates.