Tandem Addition Rearrangement Research Articles

ChemInform Abstract: Investigation of the Reaction of 2-Bromo-1-naphthol with Arylacetonitriles and LiTMP: Facile Synthesis of 3-Arylmethyl-1-hydroxynaphthalene-2-carbonitriles.

2-Bromo-1-naphthol reacts with arylacetonitriles and 3-thienylacetonitrile in the presence of LiTMP to give the rearranged 3-benzyl-1-hydroxynaphthalene-2-carbonitriles and 11-amino-5H-anthra[2,3-b]thiophen-10-one, respectively. The reactions proceed via a tandem addition–rearrangement pathway involving a non-synchronous [2 + 2] cycloaddition of an N-lithiated ketenimine and 2,3-didehydronaphthalene 1-oxide. An explanation of the orientation to and reactivity of the aforementioned aryne is presented in terms of chelation between the OLi group and the attacking nitrile nucleophile. Support for the intermediacy of 2,3-didehydronaphthalene 1-oxide was accomplished by obtaining 3-amino-1-naphthols from the reaction of 2-bromonaphthol and the appropriate lithium amide. Alternate non-aryne mechanisms were addressed, but were rejected based on experimental results.

Investigation of the reaction of 2-bromo-1-naphthol with arylacetonitriles and LiTMP: facile synthesis of 3-arylmethyl-1-hydroxynaphthalene-2-carbonitriles

2-Bromo-1-naphthol reacts with arylacetonitriles and 3-thienylacetonitrile in the presence of LiTMP to give the rearranged 3-benzyl-1-hydroxynaphthalene-2-carbonitriles and 11-amino-5H-anthra[2,3-b]thiophen-10-one, respectively. The reactions proceed via a tandem addition–rearrangement pathway involving a non-synchronous [2 + 2] cycloaddition of an N-lithiated ketenimine and 2,3-didehydronaphthalene 1-oxide. An explanation of the orientation to and reactivity of the aforementioned aryne is presented in terms of chelation between the OLi group and the attacking nitrile nucleophile. Support for the intermediacy of 2,3-didehydronaphthalene 1-oxide was accomplished by obtaining 3-amino-1-naphthols from the reaction of 2-bromonaphthol and the appropriate lithium amide. Alternate non-aryne mechanisms were addressed, but were rejected based on experimental results.

2-[(2,5-Dimethoxyphenyl)(ferrocenyl)methyl]-3,6-dimethoxybenzonitrile

The cyano group of ferrocenylacetonitrile migrates to the phenyl ring of an aryne during a tandem addition-rearrangement reaction that yields the title compound, [Fe(C5H5)(C23H22NO4)]. The two cyclopentadienyl rings of the ferrocenyl moiety are in a staggered conformation.

The Reaction of 1-Aryl-2-(4-nitrophenylsulfonyl)ethanones with α,β-Unsaturated Esters

1-Aryl-2-(4-nitrophenylsulfonyl)ethanones (1) reacted with one equiv. of α,β-unsaturated esters at 60°C to afford the tandem addition-rearrangement products (3), while at 75°C 1a reacted with two equiv. of methyl acrylate and gave an unexpected addition-rearrangement-addition-annulation product which is dimethyl 4-hydroxyl-1-(4-nitrophenyl)-4-phenyl-1,3-cyclohexyldicarboxylate (4). A mechanism is suggested.

Investigation of the Reaction of 2-Bromo-1,4-dimethoxynaphthalene and 9-Bromophenanthrene with Nitriles Under Aryne-Forming Conditions

The reaction of 2-bromo-1,4-dimethoxynaphthalene (1) and 9-bromophenanthrene (3) with nitriles 2 under base-mediated, aryne-forming conditions gives product distributions which depend upon the nature of the bromoarene, nitrile, base, and the reaction medium. Thus, treatment of 1 with arylacetonitriles 2a-d in the presence of LDA in THF or sodium amide in liquid ammonia supplies α-aryl-1,4-dimethoxy-2-naphthylacetonitriles 4a-d, presumably by the aryne arylation mechanism. In contrast, the reaction of 9-bromo-phenanthrene (3) and arylacetonitriles 2b-e with LDA in THF yields 10-arylmethyl-9- phenanthrenecarbonitriles 6b-e, most likely by the tandem addition-rearrangement pathway. When 3 reacts with 2a-c in the presence of sodium amide and liquid ammonia, α-aryl-9-phenanthrylacetonitriles 5a-c, rather than the rearranged nitriles 6a-c, are obtained. Both 1 and 3 react with alkylnitriles 2f-i and LDA-THF, sodium amide-liquid ammonia, or Caubere's sodamide base to afford aryne arylated nitriles (4f-i and 5f-i, respectively). An explanation in terms of the influence of reactants and solvent on the competition between the aryne arylation and tandem addition-rearrangement pathways is presented.

ChemInform Abstract: The Synthesis of 1‐Amino‐3,8‐dipyridylmethyl‐7‐methylisoquinoline Involving a Tandem Addition Rearrangement Aryne Reaction.

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An Investigation of the Influence of Haloarenes and Hetarylacetonitriles on the Competition between Possible Aryne Arylation and Tandem Addition-Rearrangement Pathways

Attempts to extend the LDA-mediated 1-aminoisoquinoline arynic synthesis to 1,2-dibromo-3,4,5,6-tetramethylbenzene (1a) and the hetarylacetonitriles 2-(2a) and 3-pyridylacetonitrile (2b), 2-(2c) and 3-thiophene acetonitrile (2d), and 2-benzimidizoylacetonitrile (2e) failed; only rearranged 2-hetarylmethyl-3,4,5,6-tetramethylbenzonitriles (3aa-ae) were obtained. Additionally, the reaction of 1-chloro-2,5-dimethylbenzene (1b), 2-bromo-4-methylanisole (1c), bromobenzene (1d), 2-bromoanisole (1e), and 1-bromo-2,5-dimethoxybenzene (1f) with 2a-e gave rearranged nitriles (3) by the tandem addition-rearrangement aryne pathway and/or aryne arylated nitriles (4) by the aryne arylation pathway

Synthesis and X-ray structure of a novel 9-imino derivative of anthracene

The X-ray structure of the novel title compound 1 and a possible mechanism for its formation, which involves a tandem addition–rearrangement as key steps in the reaction of 2-chloro-1,4-dimethylbenzene with 4-methoxyphenylacetonitrile and lithium diisopropylamide.

The Synthesis of 1-Amino-3,8-dipyridylmethyl-7-methylisoquinoline Involving a Tandem Addition Rearrangement Aryne Reaction

The synthesis of 1-amino-3,8-dipyridylmethyl-7-methylisoquinoline (3) accomplished by the reaction of 2-chloro-1,4-dimethylbenzene with pyridylacetonitrile under aryne forming conditions is reported. A mechanism is suggested in which a cyano group is inroduced ortho to one of the ring methyl groups via tandem-addition rearrangement aryne process. Such positioning of the cyano group facilitates lithiation of the adjacent methyl group by stabilizing the resulting CH 2 Li group by resonance delocalization. The CH 2 Li group then reacts with another molecule of pyridylacetonitrile affording a cyano-imine intermediate which condenses intramolecularly to afford 3 after a successive tautomeric shift and proton quench

Synthesis of Poly(methylphenyl)acetonitriles by the Aryne Reaction

Several 2-(arylmethyl) derivatives of 3,6-dimethyl- and 3,4,5,6-tetramethylbenzonitriles have been prepared in good yields most likely by a tandem addition-rearrangement reaction of the appropriate bromoarene and arylacetonitrile under aryne-forming conditions. Additionally, several 2-aryl-2-(1,4-dimethyl-2-naphthyl)acetonitriles were obtained by the usual aryne mechanism from the reaction of 2-bromo-1,4-dimethylnaphthalene and arylacetonitriles with lithium tetramethylpiperidide.

Preparation of 10-Amino-9-anthracenecarbonitriles from the Reaction of α-Cyano-o-tolunitrile and Haloarenes Under Aryne-Forming Conditions

α-Cyano-α-litbio-α-tolunitrile (4) undergoes cycloaddition with various methoxy substituted arynes 2 to yield 10-amino-9-anthracene-carbonitriles 5. In contrast, 3,4,5,6-tetramethylbenzyne (2f) reacts with 4 to yield 2-(2-cyanophenyl)methyl-3,4,5,6-tetramethylbenzonitrile (6), most likely by the tandem addition-rearrangement pathway

A Facile One-Step Synthesis of Novel Polysubstituted Pyridines via the Tandem-Addition Rearrangement Hetaryne Reaction

Polysubstituted pyridines have been prepared in fair yields by a one-step reaction of heteroarene 3-bromo-2,3-dimethoxy-5-(methoxymethyl)pyridine (I) and lithio alkyl- and lithio aryl-acetonitriles via heteroaryne generated from (I) by LDA in THF. Most lithio arylacetonitriles yield rearranged products by the tandem-addition rearrangement pathway and a 2:1 to 3:1 mixture of normal hetaryne products

Unsaturated carboxylic acid dienolates. Michael addition to enones through tandem 1,2-addition - oxy-cope rearrangement.

Michael addition of the dienolate derived from 2-butenoic acid to 1,3-diphenylpro-penone occurs through a 1,2-addition followed by a 3,3-sigmatropic rearrangement. α,γ -re-gioselectivity found for Michael addition to other styryl ketones depends on the steric parameter of the substituents at the carbonyl group, in agreement with the same tandem addition rearrangement mechanism.

Tandem addition-rearrangement of nitrile anions to benzyne. A convenient synthesis of 3-cyano-2-alkyl benzoic acids and benzaldehydes.

Benzynes derived from aryloxazolines react with lithio-alkyl nitriles to give addition followed by cyclization to benzocyclobutanone imines which fragment to the title products.