John M. Vernon

Enhancing the yield and diastereoselectivity of the Pictet-Spengler reaction : a highly efficient route to cis-1,3-disubstituted tetrahydro-β-carbolines

Abstract Under conditions of kinetic control, the cis-diastereoselectivity of the Pictet-Spengler reaction between tryptophan esters and aldehydes can be controlled by varying the size of the ester group; the reaction proceeds in essentially quantitative yield with most aldehydes when conducted in chloroform in the presence of molecular sieves.

Spiro cyclisations of N-acyliminium ions involving an aromatic π-nucleophile

Spiro 2-pyrrolidin-5-ones were obtained from N-substituted succinimides by a two-step procedure, involving 5- or 6-endo-trig cyclisation of N-acyliminium ion intermediates with a tethered aromatic π-nucleophile.

Chemoselective debenzylation involving removal of a 2-hydroxy-1-phenylethyl group from nitrogen

Abstract In 2-(2-hydroxy-1-phenylethyl)-1-isoindolinone, selective removal of the 2-hydroxy-1-phenylethyl group is convenienthyl achieved via a 3-step sequence (mesylation, elimination, hydrolysis) without breaking an endocyclic benzylic nitrogen bond.

Novel spiro cyclisations of N-acyliminium ions involving an aromatic π-nucleophile

Abstract Several spiro 2-pyrrolidin-5-ones were obtained by a two-step procedure from N -substituted succinimides, involving spiro cyclisation of N -acyliminium ion intermediates in refluxing trifluoroacetic acid; in all cases cyclisation utilised a tethered aromatic π-nucleophile, and ring-closure followed 5- or 6- exo-trig pathways.

Regioselective formation of hydroxy lactams from pyridine-2,3-dicarboximides and their cyclodehydration to pyrido[2',3':3,4]pyrrolo-fused heterocyclic systems

Grignard reactions of pyridine-2,3-dicarboximides involve attack at the carbonyl group closer to the pyridine nitrogen atom to give 7-hydroxypyrrolo[3,4-b]pyridin-5(7H)-one derivatives. Reduction of the same imides with sodium borohydride gives mixtures of regiosomeric hydroxy lactams, in which the 7-hydroxypyrrolo[3,4-b]pyridin-5-ones are the major components. Hydroxy lactams derived by either of these two methods from pyridine-2,3-dicarboximides containing N-benzyl, N-2-phenylethyl, N-2-(indol-3-yl)ethyl, or N-biphenyl-2-yl substituents are cyclised by heating in trifluoroacetic or polyphosphoric acid to give derivatives of new pyrido[2′,3′:3,4]pyrrolo-fused heterocyclic systems.

Nitrogen-Bridged Six-Membered Ring Systems: 7-Azabicyclo[2.2.1]hepta-2,5-dienes, Naphthalen-1,4-imines, and Anthracen-9, 10-imines

Publisher Summary The chemistry of the bicyclo[2.2.l]heptane ring system, with and without double bonds in the two-carbon bridges, includes many well-known and interesting features that illustrates important stereochemical aspects of some organic reaction mechanisms. Among derivatives of this ring system containing a heteroatom at the 7-position, 7-oxabicyclo-[2.2. l]heptanes have been most extensively studied, but the less accessible nitrogen-containing analogs have received attention only recently. This chapter focuses on the chemistry of 7-azabicyclo[2.2. l]heptadienes of mono- and dibenzo derivatives and of hydro derivatives of this ring system and for that appropriate comparisons are cited to the behavior of analogous ring systems containing other heteroatoms. The chapter discusses the syntheses, physical and spectroscopic characteristics, configurational changes at the nitrogen atom, thermal stability, aromatization, photochemistry of 7-azabicyclo[2.2.1]heptanes, 7-azabicyclo[2.2.1]heptadienes, and naphthalen-l,44mine. The syntheses, configurational changes at the nitrogen atom, ring-opening reactions, and deamination reactions of anthracen-9,10-imines are also discussed in the chapter.

Addition of benzyne to naphtho[2,3-c][1,2,5]selenadiazole

Abstract A yellow adduct obtained from benzyne and naphtho[2,3-c][1,2,5]selenadiazole is identified as 3-(10-cyano -9-anthryl)-1,2-benzisoselenazole (7). Sequential addition of dimethyl acetylenedicarboxylate and of benzyne to the same fused 1,2,5-selenadiazole affords 3-(4-cyano-2,3-bismethoxycarbonyl-1-naphthyl)-1,2-benzisoselenazole (12).

Stereospecific reduction of a β-keto-nitrile : formation of a single indolic β-hydroxy-nitrile from a mixture of tautomers and diastereoisomers

Abstract The β-keto-nitrile 2, which is an advanced intermediate for the synthesis of several indole alkaloids, is composed of a mixture of enol/keto tautomers, and of diastereoisomers; nevertheless, reduction with sodium borohydride yields essentially a single diastereoisomer 3.

Unexpected formation and crystal structure of a spiro[indene-1,7′(6′H)pyrrolo[3,4-b]pyridin]-5′-one

Dehydration of 6,7-dihydro-7-hydroxy-6-(α-methylbenzyl)-7-phenylpyrrolo[3,4-b]pyridin-5-one 4b on treatment with acid is accompanied by rearrangement, first to 6,7-dihydro-7-phenyl-7-[(E)-2-phenylethenyl]pyrrolo[3,4-b]pyridin-5-one 10 and then to 2,3-dihydro-3-phenylspiro[indene-1,7′(6′H)-pyrrolo[3,4-b]pyridin]-5′-ones 9a, b. Crystal structures of two rearranged products 9a and 10 are reported.

Reactions of tertiary allylamines with dimethyl acetylenedicarboxylate

The reaction of some tertiary allylamines with dimethyl acetylenedicarboxylate in acetonitrile results in the formation of 1 : 1 adducts via[3,3] rearrangement of the allyl group from nitrogen to carbon.