Derek H.R. Barton

The invention of new radical chain reactions. Part VIII. Radical chemistry of thiohydroxamic esters; A new method for the generation of carbon radicals from carboxylic acids

Abstract The aliphatic and alicyclic esters of N-hydroxypyridine-2-thione are readily reduced by tributylstannane in a radical chain reaction to furnish nor-alkanes.1 In the absence of the stannane a smooth decarboxylatlive rearrangement occurs to give 2-substituted thiopyridines.1 The radicals present in this reaction provoke with t -butylthiol an efficient radical reaction with formation of nor-alkane and 2-pyridyl- t -butyl disulphide.1Similarly these carbon radicals can be captured by halogen atom transfer to give noralkyl chlorides, bromides and iodides. 2 With oxygen in the presence of t-butylthiol the corresponding noralkyl hydroperoxides are formed in another radical chain reaction.3

A new method for the deoxygenation of secondary alcohols

On reaction with tributylstannane, O-cycloalkyl thiobenzoates and O-cycloalkyl S-methyl dithiocarbonates, derived from secondary alcohols, give good yields of the corresponding hydrocarbons. The mechanism of this planned reaction is radical in character and thus rearrangements common in carbocation reactions are avoided. The particular applicability of this procedure in sugar chemistry is illustrated. The reaction takes place under neutral conditions compatible with the presence of the functional groups which normally occur in aminoglycoside antibiotics.A convenient general synthesis of O-cycloalkyl thioesters has been developed which gives access to O-cycloalkyl thioformates and thioacetates. An extension of this method affords the hitherto unknown O-cycloalkyl seleno-formates and selenobenzoates. An attempted extension of the method to the synthesis of O-chloesteryl tellurobenzoate gave, unexpectedly, a good yield of benzyl cholesteryl ether.

A PRACTICAL ALTERNATIVE TO THE HUNSDIECKER REACTION

Abstract Carboxylic acid esters derived from N-hydroxy-pyridine-2-thione react with carbon tetrachloride, bromotrichloromethane or iodoform in a radical chain reaction to give the corresponding noralkyl chlorides, bromides or iodides in high yield.

An improved preparation of vinyl iodides

Abstract The oxidation of ketone hydrazones by iodine in the presence of a base to furnish vinyl iodides has been considerably improved. The three factors responsible are (1) absence of water, (2) the use of strong guanidine bases and (3) inverse addition.

The invention of radical reactions : Part XV.1Some mechanistic aspects of the decarboxylative rearrangement of thiohydroxamic esters

Abstract Esters (mixed anhydrides) derived from aliphatic or alicyclic carboxylic acids (RCO2H) and thiohydroxamic acids 2 or 3 undergo a thermally or photochemically induced radical chain reaction to give sulphides 4 with loss of carbon dioxide. On irradiation at low-temperature however, the chain reaction is essentially supressed. Under these conditions moderate to good yields of dimers R-R are obtained from primary acids. The mechanistic and synthetic implications of these observations are discussed.

On the mechanism of the deoxygenation of secondary alcohols by the reduction of their methyl xanthates by tin hydrides

Abstract Two alternate proposals for the mechanism of reduction of xanthates by tributylstannane have been examined. Evidence has been secured that under normal reduction conditions the thiocarbonyl group is attacked reversibly. At a high enough temperature the carbon radical fragments to give eventually the reduction product. Under modified conditions, where no reducing agent (Sn-H) is present, the radical formed eliminates methylthiotributylstanne and affords the thiocarbonyloxy radical observed in the e.s.r. spectrum.

Manipulation of the cabboxyl groups of α-amino-acids and peptides using radical chemistry based on esters of N-hydroxy-2-thiopyridone

Abstract Photolysis of α-amino-acid or peptide esters derived from N -hydroxy-2-thiopyridone in the presence of t -butylthiol affords the expected decarboxylation products in good yield. The reaction can be applied to the α-carboxyl or to the side chain carboxyl of glutamic and aspartic acids and thus permits the preparation of a number of useful synthons. Photolysis of side chain esters in the presence of a suitable halogen atom transfer reagent gives halides often in good yield and, especially in the case of aspartic acid derivatives, without racemisation.

The free radical chemistry of carboxylic esters of 2-selenopyridine-N-oxide: a convenient synthesis of (L)-vinylglycine

Abstract Optically pure (L)-vinylglycine has been synthesised by two different methods. The first of these involves protected (L)-glutamate esters of N -hydroxy-2-seleno-pyridine. Such esters are shown to undergo the same decarboxylotive rearrangement as their thio-analogues. Oxidative elimination of the selenopyridine residue with ozone, and with the aid of hex-1-ene as sacrificial olefin for the work-up, gave the desired (L)-vinylglycine derivatives. Similarly, the modified Hunsdiecker reaction on the terminal carboxyl of suitably protected (L)-glutamic derivatives gave the nor-bromide which readily afforded the corresponding phenylselenides on treatment with phenylselenide anion. The sequence was then as above. Using the methyl ester with corbobenzyloxy protection for the amino-function an overall yield of crystalline optically pure (L)-vinylglycine of about 45% was obtained by either route.

Studies on the oxidation of hydrazones with iodine and with phenylselenenyl bromide in the presence of strong organic bases; an improved procedure for the synthesis of vinyl iodides and phenyl-vinyl selenides

Abstract The oxidation of hydrazones by iodine in the presence of strong organic bases (guanidines) has been studied. Improved yields of vinyl iodides can be obtained by inverse addition using dry solvents and with a final heating period where appropriate. The reaction has been extended to various dihydrazones with interesting results. In complementary studies hydrazones have been oxidized by phenylselenenyl bromide in the presence of strong organic bases to give the corresponding phenyl vinyl selenides in good yield.

The invention of new radical chain reactions. part X1: High yield radical addition reactions of αβ-unsaturated nitroolefins. An expedient construction of the 25-hydroxy-vitamin D3 side chain from bi

Abstract Radicals derived from thiohydroxamic esters 3 readily add to nitroolefins 5 (Z = NO2) to give good yields of α-nitrosulphides. These adducts, where the structure permits, are easily oxidised to carboxylic acids 8 by treatment with alkaline hydrogen peroxide. Reductive cleavage to the corresponding aldehydes or ketones 9 is efficiently carried out by the action of TiCl3. Addition of methyl magnesium iodide to the methyl ketone derived from 3α-acetoxy 11-oxo cholanic acid gives steroid 10 possessing the 25-hydroxycholesterol side chain of the vitamin D3 metabotites. Radical additions to 1-phenylthio-2-nitropropene 11 have been briefly studied.