The Astounding Chemistry of a 2-Amino-1,2-dihydroisoquinoline Derivative

Abstract

Dedicated to Professor Albert Eschenmoser on the occasion of his 75th birthday The cycloadducts of isoquinolinium N-phenyl imide 2 with CC bonds are derivatives of 2-amino-1,2-dihydroisoquinoline. Their N b -vinylphenylhydrazine system is amenable to an acid-catalyzed [3,3]-sigmatropic shift; the formation of pentacyclic aminals is exemplified by 6 3 8. The dimethyl maleate adduct 11, C 21 H 20 N 2 O 4 , is exceptional by being converted on treatment with acid to bright-yellow crystals, C 24 H 22 N 2 O 6 (additional C 3 H 2 O 2 ). X-Ray crystal-structure analysis and NMR spectra reveal structure 13, and mechanistic studies indicated an initial b-elimination at the NÀN bond of 11 to yield 18; this step is followed by a retro-Mannichtype cleavage that gives methyl isoquinoline-1-acetate (14) and methyl 2-(phenylimino)acetate (15), according to the sequence C 21 H 20 N 2 O 4 (11) 3 18 3 C 12 H 11 NO 2 (14) C 9 H 9 NO 2 (15). In the second act of the drama, electrophilic attack by 15-H on the ene-hydrazine group of a second molecule of 11 furnishes 13 by a polystep intramolecular redox reaction. All rate constants must be fine-tuned in this reaction cascade to give 13 in yields of up to 78% with an overall stoichiometry: 2 C 21 H 20 N 2 O 4 (11) 3 C 24 H 22 N 2 O 6 (13) C 12 H 11 NO 2 (14) aniline. Interception and model experiments confirmed the above pathway. A by-product, C 33 H 31 N 3 O 6 (62), arises from an acid-catalyzed dimerization of 11 and subsequent elimination of 15.

A Rearrangement of 3-Pyrazolines as a Missing Link

“…Cycloadduct 14 is formed by the reaction of isoquinolinium N-phenylimide with dimethyl maleate [19]. We reported recently on the conversion of two molecules of 14 by treatment with acid to give the triester 15 [1]. The structure of 15 was confirmed by X-ray analysis [20]; methyl isoquinoline-1-acetate and aniline were further products.…”

“…More than 1 mol-equiv. of H 2 was consumed in the hydrogenation of 21, and 30% of 24 was isolated; the same compound 24 was also formed from 14 by treatment with an acidic buffer [1].…”

3-Pyrazolines (2,3-dihydro-1H-pyrazoles): synthesis, reactivity, and physical and biological properties

“…113 A further fifteen years passed before the mechanism was published for the transformation of pyrazolidine 112, obtained from the dipole 111 and dimethyl maleate, into the 3-pyrazoline 113 with an unexpected supplementary CH2CO2CH3 arm (Scheme 30). 114,115 Scheme 30. Synthesis of 3-pyrazoline 113.…”

Synthesis of Cyclic Hydrazino α-Carboxylic Acids

“…Dipoles 15 react in [3+2] cycloadditions with l y d i a m y c i n A l y d i a m y c i n B l y d i a m y c i n C l y d i a m y c i n D H H -C H 2 -N H -O H H -C H 2 -N H -H H -C H = N -H O H -C H 2 -N H - both electron-poor and electron-rich dipolarophiles (Sustmann's class II dipoles 46 ) to give cycloadducts 17. 47 If monosubstituted alkenes 16 are used as dipolarophiles, the resulting cycloadducts are obtained with high regioselectivity. 48 Dipoles for cycloadditions have also been generated by thermal decomposition of cyclic aminals like 19 which are easily accessible from chiral amino alcohols.…”