John T. Pinhey

Reaction of arylboronic acids and their derivatives with lead tetra-acetate. The generation of aryl–lead triacetates, and meta- and para-phenylenebis(lead triacetate), in situ for electrophilic arylation

Arylboronic acids and some of their derivatives have been found to undergo a rapid boron–lead exchange with lead tetra-acetate. In the presence of a catalytic amount of mercury(II) acetate, the reaction produces mainly the aryl–lead triacetate, and it has been developed as a convenient method for in situ generation of these useful electrophilic C-arylating reagents. The reaction allows the generation for the first time of meta- and para-phenylenebis(lead triacetate), compounds which behave as meta- and para-phenylene dication equivalents.

The α-arylation of derivatives of malonic acid with aryllead triacetates. New syntheses of ibuprofen and phenobarbital.

Abstract Derivatives of Meldrums acid and the sodium salts of substituted malonic esters undergo rapid arylation in high yield when treated with aryllead triacetates. These reactions have been applied to the synthesis of ibuprofen, an analgesic, and in a closely related reaction 5-ethylbarbituric acid has been reacted with phenyllead triacetate to give phenobarbital.

The α-alk-1-ynylation of β-dicarbonyl compounds and nitronate salts by alk-1-ynyl-lead triacetates

Di(alk-1-ynyl)mercury compounds and alk-1-ynyltrimethylstannanes have been shown to react with lead tetra-acetate to give alk-1-ynyl-lead triacetates, unstable intermediates which may be used for the C-alkynylation of β-dicarbonyl compounds and the salts of nitroalkanes. A comparative study of the two methods has shown that the tin–lead exchange route to the alkynyl-lead intermediate results in better yields, and in an examination of the scope of this alkynylation procedure the acetylene derivatives (5), (9)–(14), (27)–(30), (32), (34), (36)–(41), (43), (45), (47)–(49), and (51)–(56) have been produced in moderate to good yields.

A general method for removal of a 4-methyl group from triterpenoids. Synthesis of 4β-demethylglycyrrhetinic acid

Using 4,4-dimethyl-5α-cholestan-3-one (1) as a model compound, a short high-yielding sequence has been developed for removing a 4-methyl group from triterpenoids. The method makes use of the ‘abnormal’ Beckmann reaction which 3-hydroxyimino-4,4-dimethylsteroids undergo to yield 3,4-seco-nitriles. Epoxidation of the 4-methylene group, followed by treatment of the 3,4-seco-epoxy-nitrile with boron trifluoride in refluxing toluene affords the 4β-demethyl-3-ketone in an overall yield of 40–50%. The general nature of the method has been demonstrated in the conversion of dihydrolanosterol into 4α,14α-dimethyl-5α-cholest-8-en-3-one (17) and 4α,14α-dimethyl-5α-cholestane-3,11-dione (3), and in the synthesis of 3β-hydroxy-11-oxo-24-nor-18β-olean-12-en-30-oic acid (4β-demethylglycyrrhetinic acid)(27) and 3,11-dioxo-24-nor-18β-olean-12-en-30,22β-olactone (31).

Aryl fluoride syntheses involving reaction of aryllead triacetates with boron trifluoride-diethyl ether complex

Abstract Aryllead(IV) triacetates react at room temperature with BF 3 .Et 2 O to give the corresponding aryl fluoride in moderate to good yields; triarylboroxines, electron rich aryltrimethylsilanes and some arenes, which yield aryllead triacetates in acid catalysed reactions with lead tetraacetate, are converted directly into aryl fluorides when stirred with lead tetraacetate in BF 3 .Et 2 O. An investigation of the mechanism of the fluoro-deplumbation reaction indicates that it probably proceeds by acid catalysed heterolytic cleavage of the CPb bond to produce an aryl cation.

The arylation of nitroalkanes and nitronate salts with aryllead triacetates

Abstract Nitroalkanes and their nitronate salts undergo α-arylation in good yield when treated with an aryllead triacetate in dimethyl sulfoxide.

Synthesis of aryllead(iv) triacetates by tin-lead exchange

Abstract Aryltributylstannanes undergo a high yielding mercury (II) catalysed reaction with lead tetraacetate in chloroform to give the aryllead triacetate, which is readily separated from the other product of the reaction, tributyltin acetate. The synthetic utility of the reaction is demonstrated in the preparation of 6-methoxy-2-naphthyllead triacetate which is readily converted into the anti-inflammatory drug, naproxen.

Use of the electrophilic arylation reaction of aryl-lead triacetates in a synthesis of (±)-lycoramine

A formal total synthesis of (±)-lycoramine is reported. The quaternary carbon centre of the alkaloid was produced by a novel electrophilic arylation of the mixture of isomeric vinylogous keto esters (4) and (5) by 2,3-dimethoxyphenyl-lead triacetate. The resulting key intermediate (7c), which was formed in almost quantitative yield, was converted in a straightforward sequence into the formamide (25), from which the alkaloid has been produced previously by a Bischler-Napieralski cyclisation. Functional group protection was only required at one stage in the synthesis.

‘Alk-l-ynyllead triacetates’ as alk-1-ynyl carbocation equivalents. The α-alk-1-ynylation of β-dicarbonyl compounds and nitronate salts

Abstract The addition of lead tetraacetate to a chloroform solution of alk-l-ynyltrimethylstannane results in the rapid formation of trimethylstannyl acetate and an unstable species, believed to be the corresponding alk-l-ynyllead triacetate, which can effect the rapid α-alkynylation of β-dicarbonyl compounds and nitronate salts.

α-Alkenylation of β-dicarbonyl compounds with ‘alk-1-enyl-lead triaetates’

Addition of lead tetra-acetate to a chloroform solution fo a dialk-1-enylmercury or an alk-1-enyltributylstannane results in rapid formation of a relatively unstable species, believed to be an alk-1-enyl-lead triacetat, which can be used for the α-alkenylation of β-dicarbonyl compounds.