Thomas L. Gilchrist

A short synthesis of phenanthro[2,3-d]imidazoles from dehydroabietic acid. Application of the methodology as a convenient route to benzimidazoles

Abstract Methyl cis -deisopropyldehydroabietate was selectively nitrated at the 12-position by reaction with ‘claycop’, a montmorillonite clay impregnated with copper(II) nitrate. The 12-nitro compound was reduced to the corresponding amine and this was subjected to a combined acylation and ortho nitration. The compounds so produced were further converted into octahydro-1 H -phenanthro[2,3- d ]imidazoles by reductive cyclization. The same acylation- ortho nitration methodology was shown to provide a short synthesis of 2-substituted benzimidazoles from aniline.

Synthesis of 3-substituted furans by directed lithiation and palladium catalysed coupling

Abstract The 5-position of the furan ring of 4,4-dimethyl-2-(2-furyl)oxazoline ( 1a ) was protected by a trimethylsityl group. The product, compound ( 2a ), was then lithiated at the 3-position with sec-butyllithium and converted to the bromozinc species ( 2d ) with zinc bromide. Coupling reactions with a range cf aryl-, acyl-, and vinyl halides were performed with Pd(PPh3) 4 as catalyst. The reaction with (l-bromoethenyl)- trimethylsilane is abnormal in that it gives a mixture of two products ( 2l ) and ( 2m ). The origin of the abnormal product ( 2l ) is discussed. The coupling reactions of this silane with 2-thienyl-, 2-furyl-, and phenyl-zinc bromide have also been carried out: in each case, a mixture of the expected coupling product and an isomer, the ethen-2-yltrimethylsilane, was obtained. The ratio of products is shown to depend upon the temperature at which the coupling is carried out. 4,4-Dimethyl-2-(2-thienyl)oxazoline ( 1b ) was lithiated at the 3-position of the thiophene ring and coupled to iodobenzene without protection of the 5 -position.

1—Azatriene cyclisation as a route to annelated pyrido[4,3-b]indoles☆

Abstract Derivatives of indole-3-carbaldehyde oxime have been prepared that bear a carbon-carbon double bond at C-2 and a five- or six-membered ring linking the α-carbon artom of the vinyl group and the indole nitrogen atom. Compound 9, with a five-membered ring linking the two atoms, failed to undergo a cyclisation reaction on heating. However the oximes 16 and 22, with a six-memberd ring linking the two atoms, cyclised in boiling toluene. The cyclisation led to the formation of the pyrido-indoles 17 and 18, respectively.

Ethyl 3-bromo-2-hydroxyiminopropanoate, a reagent for the preparation of ethyl esters of α-amino acids

The title compound (1) reacts with a variety of nucleophiles in the presence of sodium carbonate to give α-hydroxyimino esters, which can be reduced to α-amino esters.

GENERATION AND DIELS-ALDER REACTIONS OF T-BUTYL 2H-AZIRINE-3-CARBOXYLATE

Abstract The azirinyl ester 2 (R = Bu t ) has been generated by thermolysis of t-butyl 2-azidoacrylate. It is too unstable to allow its full characterisation but it has been intercepted by Diels-Alder cycloaddition to several dienes. Addition to a chiral diene 8 is highly diastereoselective.

Synthesis of isoquinolines by cycloaddition of arynes to 1,2,4-triazines

Abstract Benzyne has been generated from benzenediazonium-2-carboxylate in the presence of several 1,2,4-triazines 1 and isoquinolines 2 have been isolated in moderate yield. 1-Aminobenzotriazole was also used as the source of benzyne and isoquinolines were again isolated in moderate yield from these reactions. 4-Methylbenzyne, which was generated from 5-methylanthranilic acid, reacted unselectively with the triazines to give mixtures of 6- and 7-methylisoquinolines 3 and 4 On the other hand reactions of 3-methylbenzyne with the triazines 1d and 1e proceeded with high regioselectivity, giving only the 5-methylisoquinoline 5a and the 8-methylisoquinoline 6b, respectively.

Diels-alder cycloaddition reactions of αβ-unsaturated aldehyde acylhydrazones

Abstract Acylhydrazones derived from N -methyl- N -pent-4-enoylhydrazine or N -methyl- N -pent-4-ynoylhydrazine and αβ-unsaturated aldehydes undergo intramolecular Diels-Alder reactions at elevated temperatures. An intermolecular counterpart, the addition of methacrolein benzoylhydrazone to N -phenylmaleimide, has also been carried out.

DIELS-ALDER REACTIONS OF 2-AZADIENES DERIVED FROM CYSTEINE AND SERINE METHYL ESTERS AND ALDEHYDES

Abstract The Diels-Alder reactions of N-benzylidenedehydroalanine methyl ester 1a with but-3-en-2-one and with other electron deficient dienophiles have been found to give new dihydro- and tetrahydropyridines. The cycloaddition reactions are regioselective but not stereoselective. Cycloaddition reactions between 1a and enamines have also been observed. The [4 + 2] cycloaddition reactions of other N-arylidenedehydroalanine methyl esters are also reported. Two new types of azadiene were prepared, namely N-(benzoylmethylene)dehydroalanine methyl ester 1e and N-(ethoxycarbonylmethylene)dehydroalanine methyl ester 1f. Their reactions with N-cyclohexen-1-ylpyrrolidine and with N-cyclopenten-1-ylpyrrolidine have led to the isolation of the dihydropyridine and pyridine esters.

Preparation of 1-substituted-3,4-dihydronaphthalene-2-carboxaldehyde N,N-dimethylhydrazones by palladium(0) coupling, and their electrocyclic ring closure

Abstract 1-Bromo-3,4-dihydronaphthalene-2-carboxaldehyde 2 has been converted by three methods, each involving halogen-metal exchange and palladium(0) catalysed cross coupling, into N,N-dimethylhydrazones of 1-aryl- and 1-vinyl-3,4-dihydronaphthalene-2- carboxaldehydes. The N,N-dimethylhydrazone 10 of the aldehyde 2 undergoes efficient bromine-lithium exchange with butyllithium, as does 2-bromobenzaldehyde N,N-dimethylhydrazone 17. The dimethylhydrazones of 1-vinyl-3,4-dihydronaphthalene-2-carboxaldehydes were not isolated by underwent electrocyclic ring closure followed by loss of dimethylamine in solution to give 5,6-dihydrobenz[f]isoquinolines. 1-Aryl-3,4-dihydronaphthalene-2- carboxaldehyde N,N-dimethylhydrazones also cyclised in the same way when subjected to vapour phase pyrolysis.

The cycloaddition of α-nitrosostyrenes to olefins. Investigations of the scope and mechanism of the reaction

Cycloaddition of α-nitrosostyrene (1a) to several substituted styrenes is shown to give 3-phenyl-5,6-dihydro-4H-1,2-oxazines (2) in moderate yield. Reactions with 4-nitro-α-nitrosostyrene (1b) give better yields of the corresponding adducts (3). The preferred conformations of the adducts are deduced from their n.m.r. spectra. The observed regio- and stereo-selectivities of the additions are interpreted in terms of a one-step addition in which the olefins act as the donor components.The first example of a formal 1,3-dipolar addition of a vinyl nitroso compound is provided by the formation of the nitrone (5) as a minor product of the reaction of α-nitrosostyrene with 2-methoxypropene. The relative yield of this nitrone is not increased by the change to a more polar solvent, nor by the use of α-bromoacetophenone anti-oxime in place of the usual syn isomer as the precursor of α-nitrosostyrene. It is suggested that this, and other minor products (4) isolated from the cycloadditions, may be formed because of steric inhibition of the usual Diels–Alder-type process.